Usher syndrome type I (USH1) is characterized by congenital deafness, vestibular areflexia, and p... more Usher syndrome type I (USH1) is characterized by congenital deafness, vestibular areflexia, and progressive retinal degeneration with age. The protein-truncating p.Arg245* founder variant of PCDH15 has an ~2% carrier frequency among Ashkenazi Jews, accounting for nearly 60% of their USH1 cases. Here, longitudinal ocular phenotyping in thirteen USH1F individuals harboring the p.Arg245* variant revealed progressive retinal degeneration, leading to severe loss of vision with macular atrophy by the sixth decade. Half of the affected individuals met either the visual acuity or visual field loss definition for legal blindness by the middle of their fifth decade of life. Mice homozygous for p.Arg250* (Pcdh15R250X; equivalent to human p.Arg245*) also have early visual deficits evaluated using electroretinography. Light-dependent translocation of phototransduction cascade proteins, arrestin and transducin, was found to be impaired in Pcdh15R250X mice. Retinal pigment epithelium-(RPE) specifi...
Age-related macular degeneration (AMD) is a multifactorial neurodegenerative disorder. Although m... more Age-related macular degeneration (AMD) is a multifactorial neurodegenerative disorder. Although molecular mechanisms remain elusive, deficits in autophagy have been associated with AMD. Here we show that deficiency of calcium and integrin binding protein 2 (CIB2) in mice, leads to age-related pathologies, including sub-retinal pigment epithelium (RPE) deposits, marked accumulation of drusen markers APOE, C3, Aβ, and esterified cholesterol, and impaired visual function, which can be rescued using exogenous retinoids. Cib2 mutant mice exhibit reduced lysosomal capacity and autophagic clearance, and increased mTORC1 signaling—a negative regulator of autophagy. We observe concordant molecular deficits in dry-AMD RPE/choroid post-mortem human tissues. Mechanistically, CIB2 negatively regulates mTORC1 by preferentially binding to ‘nucleotide empty’ or inactive GDP-loaded Rheb. Upregulated mTORC1 signaling has been implicated in lymphangioleiomyomatosis (LAM) cancer. Over-expressing CIB2 i...
Melanin pigment helps protect our body from broad wavelength solar radiation and skin cancer. Amo... more Melanin pigment helps protect our body from broad wavelength solar radiation and skin cancer. Among other pigmentation disorders in humans, albinism is reported to manifest in both syndromic and nonsyndromic forms as well as with varying inheritance patterns. Oculocutaneous albinism (OCA), an autosomal recessive nonsyndromic form of albinism, presents as partial to complete loss of melanin in the skin, hair, and iris. OCA has been known to be caused by pathogenic variants in seven different genes, so far, according to all the currently published population studies. However, the detection rate of alleles causing OCA varies from 50% to 90%. One of the significant challenges of uncovering the pathological variant underlying disease etiology is inter- and intra-familial locus heterogeneity. This problem is especially pertinent in highly inbred populations. As examples of such familial locus heterogeneity, we present nine consanguineous Pakistani families with segregating OCA due to vari...
Otitis media (OM) is an infective and inflammatory disorder known to be a major cause of hearing ... more Otitis media (OM) is an infective and inflammatory disorder known to be a major cause of hearing impairment across all age groups. Both acute and chronic OM result in substantial healthcare utilization related to antibiotic prescription and surgical procedures necessary for its management. Although several studies provided evidence of genetics playing a significant role in the susceptibility to OM, we had limited knowledge about the genes associated with OM until recently. Here we have summarized the known genetic factors that confer susceptibility to various forms of OM in mice and in humans and their genetic load, along with associated cellular signaling pathways. Spotlighted in this review are fucosyltransferase (FUT) enzymes, which have been implicated in the pathogenesis of OM. A comprehensive understanding of the functions of OM-associated genes may provide potential opportunities for its diagnosis and treatment.
A detailed comparison of subharmonic synchronous mode-locking and subharmonic hybrid mode-locking... more A detailed comparison of subharmonic synchronous mode-locking and subharmonic hybrid mode-locking of a monolithic DBR laser is presented. While subharmonic electrical injection offers ease of implementation, subharmonic optical injection offers advantages of reduced amplitude modulation and larger locking ranges
The accuracy of the Content should not be relied upon and should be independently verified with p... more The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden.
Proceedings of Optical Fiber Communication Conference (, 1997
Millimeter-wave (mm-wave) optical fiber transport links will greatly simplify the architectures o... more Millimeter-wave (mm-wave) optical fiber transport links will greatly simplify the architectures of future high-capacity cellular systems, indoor wireless LANs and video-on-demand systems. In addition to supporting low loss and EMI free transport of broadband signals, these links enable deployment of miniature, functionally simple and easily installable radio infrastructure at signals distribution points. Attempts towards implementing mm-wave signal distribution schemes have
JPMA. The Journal of the Pakistan Medical Association, 2006
To assess the relative frequency of (primary and secondary) mammary lymphomas presenting to a ter... more To assess the relative frequency of (primary and secondary) mammary lymphomas presenting to a tertiary care hospital, Pakistan and its categorization according to WHO classification of lymphoid neoplasms. All NHLs (nodal and extra nodal) diagnosed in the section of histopathology during 1992-2004 were retrieved and reviewed. All patients (n=30) diagnosed with lymphomatous involvement of the breast were selected. Distinction between primary and secondary breast lymphomas was not made owing to lack of availability of clinical information. A total of 5637 breast malignancies were diagnosed in our department during the study period of 10 years and the total number of NHLs (Nodal and extra Nodal) was 2632. Thirty (n=30) patients accounting for 1.13% were diagnosed to have lymphomatous involvement of the breast. The Female to Male ratio was 13.5:1; age range was 12-92 years with a median age of 43 years (Mean age 46.5 years and Standard deviation of age was 16.88 years). The sites of the ...
Mutant alleles of TMPRSS3 are associated with nonsyndromic recessive deafness (DFNB8/B10). TMPRSS... more Mutant alleles of TMPRSS3 are associated with nonsyndromic recessive deafness (DFNB8/B10). TMPRSS3 encodes a predicted secreted serine protease, although the deduced amino acid sequence has no signal peptide. In this study, we searched for mutant alleles of TMPRSS3 in families from Pakistan and Newfoundland with recessive deafness co-segregating with DFNB8/B10 linked haplotypes and also more thoroughly characterized the genomic structure of TMPRSS3. We enrolled families segregating recessive hearing loss from Pakistan and Newfoundland. Microsatellite markers flanking the TMPRSS3 locus were used for linkage analysis. DNA samples from participating individuals were sequenced for TMPRSS3. The structure of TMPRSS3 was characterized bioinformatically and experimentally by sequencing novel cDNA clones of TMPRSS3. We identified mutations in TMPRSS3 in four Pakistani families with recessive, nonsyndromic congenital deafness. We also identified two recessive mutations, one of which is novel,...
Journal of community hospital internal medicine perspectives, 2014
Acquired adult-onset zinc deficiency is occasionally reported in patients with malnutrition state... more Acquired adult-onset zinc deficiency is occasionally reported in patients with malnutrition states, such as alcoholism, or malabsorptive states, such as post-bariatric surgery. The defining symptoms of hypozincemia include a classic triad of necrolytic dermatitis, diffuse alopecia, and diarrhea. We report a case of zinc deficiency in a 39-year-old man with history of gastric bypass surgery and alcoholism. For this patient, severe hypozincemia confirmed acrodermatitis, and zinc supplementation was met with gradual improvement.
2009 IEEE 13th International Multitopic Conference, 2009
Abstract A fractal monopole antenna based on the Sierpinski gasket is studied in this paper. The... more Abstract A fractal monopole antenna based on the Sierpinski gasket is studied in this paper. The monopole antenna based on the Sierpinski gasket constructed through three iterations displays a multiband behaviour with three bands that are log-periodically spaced by a ...
The reliability concept provides a means of incorporating some degree of certainty into the pavem... more The reliability concept provides a means of incorporating some degree of certainty into the pavement design process to ensure that the outcomes of the process will provide acceptable levels of service until the end of the intended design life. Pavement structural performance and rehabilitation design are highly dependent on the in situ layer properties. Pavement layer thickness is an essential input in backcalculation analysis performed with measured surface deflections to evaluate the in situ structural capacity of a pavement. Inaccurate thickness information may lead to significant errors in the backcalculated layer moduli and, hence, in the rehabilitation design. Because pavement layer thickness has some degree of variability (normal variability), it is important to consider this variability in the backcalculation analysis and rehabilitation design. A procedure was developed to implement the reliability concept in backcalculation analysis to account for the normal variability in layer thickness within structurally homogeneous sections. This procedure was developed on the basis of in situ layer information obtained from a ground-penetrating radar study performed for the New Jersey Department of Transportation. This paper provides an overview of the procedure, along with the results of the pilot implementation of the procedure. This reliability procedure complements the reliability factor of the 1993 AASHTO pavement design guide, as the latter reliability factor does not account for the in situ layer thickness.
Intravitreal inflammation, induced by either lens injury, or intravitreal injection of zymosan (I... more Intravitreal inflammation, induced by either lens injury, or intravitreal injection of zymosan (IVZ), protects RGC from apoptosis and stimulates axon regeneration after optic nerve transection. Here, we investigate the differential effects of intra-optic nerve zymosan (ONZ) and IVZ injections on RGC neuroprotection and axogenesis. After both IVZ and ONZ injection, zymosan-induced inflammation promoted a similar 4-/5-fold enhancement in RGC survival, compared to optic nerve transected controls, but only IVZ promoted RGC axon regeneration. IVZ was the most effective in activating retinal astrocyte/Müller cells while regulated intramembraneous proteolysis (RIP) of p75(NTR) and inactivation of Rho (key components of the axon growth inhibitory signalling cascade) occurred in both ONZ and IVZ, but only in the latter did RGC axons regenerate. We suggest that neuroprotective factors may be transported to RGC somata by retrograde transport after ONZ and diffuse into the retina after IVZ injection, but an axogenic agent is required to initiate and maintain disinhibited RGC axon regeneration that may be an exclusive property of a Müller cell-derived factor released after IVZ.
In the injured central nervous system (CNS), transforming growth factor (TGF)-β1/2-induced scarri... more In the injured central nervous system (CNS), transforming growth factor (TGF)-β1/2-induced scarring and wound cavitation impede axon regeneration implying that a combination of both scar suppression and axogenic treatments is required to achieve functional recovery. After treating acute and chronic dorsal funicular spinal cord lesions (DFL) in adult rats with the pan-TGF-β1/2 antagonist Decorin, we report that in: (1), acute DFL, the development of all injury parameters was significantly retarded e.g., wound cavity area by 68%, encapsulation of the wound by a glia limitans accessoria (GLA) by 65%, GLA basal lamina thickness by 94%, fibronectin, NG2 and Sema-3A deposition by 87%, 48% and 48%, respectively, and both macrophage and reactive microglia accumulations by 60%; and (2), chronic DFL, all the above parameters were attenuated to a lesser extent e.g., wound cavity area by 11%, GLA encapsulation by 25%, GLA basal lamina thickness by 31%, extracellular fibronectin, NG2 and Sema-3A deposition by 58%, 22% and 29%, respectively, and macrophage and reactive microglia accumulations by 44%. Moreover, in acute and chronic DFL, levels of tissue plasminogen activator (tPA) were raised (by 236% and 482%, respectively), as were active-MMP-2 (by 64% and 91%, respectively) and active-MMP-9 (by 122% and 18%, respectively), while plasminogen activator inhibitor-1 (PAI-1) was suppressed (by 56% and 23%, respectively) and active-TIMP-1 and active TIMP-2 were both lower but only significantly suppressed in acute DFL (by 56 and 21%, respectively). These findings demonstrate that both scar tissue mass and cavitation are attenuated in acute and chronic spinal cord wounds by Decorin treatment and suggest that the dominant effect of Decorin during acute scarring is anti-fibrogenic through suppression of inflammatory fibrosis by neutralisation of TGF-β1/2 whereas, in chronic lesions, Decorin-induction of tPA and MMP (concomitant with reduced complimentary levels of TIMP and PAI-1) leads to dissolution of the mature established scar by fibrolysis. Decorin also promoted the regeneration of similar numbers of axons through acute and chronic wounds. Accordingly, intrathecal delivery of Decorin offers a potential translatable treatment for scar tissue attenuation in patients with spinal cord injury.
... 3 Mixing speed effect with 3 mg/L of PAC at 40 and 400 rpm ... 50% of media leads to clogging... more ... 3 Mixing speed effect with 3 mg/L of PAC at 40 and 400 rpm ... 50% of media leads to clogging phenomena or a decrease in porosity because of accumulated suspended solids (SS) and ... In addition, the recycle of backwash solids did not affect the over-all treatment process on a ...
Usher syndrome (USH) is a hereditary disorder associated with sensorineural hearing impairment, p... more Usher syndrome (USH) is a hereditary disorder associated with sensorineural hearing impairment, progressive loss of vision attributable to retinitis pigmentosa and variable vestibular function. Three clinical types have been described with type I (USH1) being the most severe. To date six USH1 loci have been reported. We ascertained two large Pakistani consanguineous families segregating profound hearing loss, vestibular dysfunction, and retinitis pigmentosa, the defining features of USH1. In these families we excluded linkage of USH to the 11 known USH loci, and subsequently performed a genome-wide linkage screen. We found a novel USH1 locus designated USH1H that mapped to chromosome 15q22-23 in a 4.92 cM interval. This locus overlaps the non-syndromic deafness locus DFNB48 raising the possibility that the two disorders may be caused by allelic mutations.
Usher syndrome type I (USH1) is characterized by congenital deafness, vestibular areflexia, and p... more Usher syndrome type I (USH1) is characterized by congenital deafness, vestibular areflexia, and progressive retinal degeneration with age. The protein-truncating p.Arg245* founder variant of PCDH15 has an ~2% carrier frequency among Ashkenazi Jews, accounting for nearly 60% of their USH1 cases. Here, longitudinal ocular phenotyping in thirteen USH1F individuals harboring the p.Arg245* variant revealed progressive retinal degeneration, leading to severe loss of vision with macular atrophy by the sixth decade. Half of the affected individuals met either the visual acuity or visual field loss definition for legal blindness by the middle of their fifth decade of life. Mice homozygous for p.Arg250* (Pcdh15R250X; equivalent to human p.Arg245*) also have early visual deficits evaluated using electroretinography. Light-dependent translocation of phototransduction cascade proteins, arrestin and transducin, was found to be impaired in Pcdh15R250X mice. Retinal pigment epithelium-(RPE) specifi...
Age-related macular degeneration (AMD) is a multifactorial neurodegenerative disorder. Although m... more Age-related macular degeneration (AMD) is a multifactorial neurodegenerative disorder. Although molecular mechanisms remain elusive, deficits in autophagy have been associated with AMD. Here we show that deficiency of calcium and integrin binding protein 2 (CIB2) in mice, leads to age-related pathologies, including sub-retinal pigment epithelium (RPE) deposits, marked accumulation of drusen markers APOE, C3, Aβ, and esterified cholesterol, and impaired visual function, which can be rescued using exogenous retinoids. Cib2 mutant mice exhibit reduced lysosomal capacity and autophagic clearance, and increased mTORC1 signaling—a negative regulator of autophagy. We observe concordant molecular deficits in dry-AMD RPE/choroid post-mortem human tissues. Mechanistically, CIB2 negatively regulates mTORC1 by preferentially binding to ‘nucleotide empty’ or inactive GDP-loaded Rheb. Upregulated mTORC1 signaling has been implicated in lymphangioleiomyomatosis (LAM) cancer. Over-expressing CIB2 i...
Melanin pigment helps protect our body from broad wavelength solar radiation and skin cancer. Amo... more Melanin pigment helps protect our body from broad wavelength solar radiation and skin cancer. Among other pigmentation disorders in humans, albinism is reported to manifest in both syndromic and nonsyndromic forms as well as with varying inheritance patterns. Oculocutaneous albinism (OCA), an autosomal recessive nonsyndromic form of albinism, presents as partial to complete loss of melanin in the skin, hair, and iris. OCA has been known to be caused by pathogenic variants in seven different genes, so far, according to all the currently published population studies. However, the detection rate of alleles causing OCA varies from 50% to 90%. One of the significant challenges of uncovering the pathological variant underlying disease etiology is inter- and intra-familial locus heterogeneity. This problem is especially pertinent in highly inbred populations. As examples of such familial locus heterogeneity, we present nine consanguineous Pakistani families with segregating OCA due to vari...
Otitis media (OM) is an infective and inflammatory disorder known to be a major cause of hearing ... more Otitis media (OM) is an infective and inflammatory disorder known to be a major cause of hearing impairment across all age groups. Both acute and chronic OM result in substantial healthcare utilization related to antibiotic prescription and surgical procedures necessary for its management. Although several studies provided evidence of genetics playing a significant role in the susceptibility to OM, we had limited knowledge about the genes associated with OM until recently. Here we have summarized the known genetic factors that confer susceptibility to various forms of OM in mice and in humans and their genetic load, along with associated cellular signaling pathways. Spotlighted in this review are fucosyltransferase (FUT) enzymes, which have been implicated in the pathogenesis of OM. A comprehensive understanding of the functions of OM-associated genes may provide potential opportunities for its diagnosis and treatment.
A detailed comparison of subharmonic synchronous mode-locking and subharmonic hybrid mode-locking... more A detailed comparison of subharmonic synchronous mode-locking and subharmonic hybrid mode-locking of a monolithic DBR laser is presented. While subharmonic electrical injection offers ease of implementation, subharmonic optical injection offers advantages of reduced amplitude modulation and larger locking ranges
The accuracy of the Content should not be relied upon and should be independently verified with p... more The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden.
Proceedings of Optical Fiber Communication Conference (, 1997
Millimeter-wave (mm-wave) optical fiber transport links will greatly simplify the architectures o... more Millimeter-wave (mm-wave) optical fiber transport links will greatly simplify the architectures of future high-capacity cellular systems, indoor wireless LANs and video-on-demand systems. In addition to supporting low loss and EMI free transport of broadband signals, these links enable deployment of miniature, functionally simple and easily installable radio infrastructure at signals distribution points. Attempts towards implementing mm-wave signal distribution schemes have
JPMA. The Journal of the Pakistan Medical Association, 2006
To assess the relative frequency of (primary and secondary) mammary lymphomas presenting to a ter... more To assess the relative frequency of (primary and secondary) mammary lymphomas presenting to a tertiary care hospital, Pakistan and its categorization according to WHO classification of lymphoid neoplasms. All NHLs (nodal and extra nodal) diagnosed in the section of histopathology during 1992-2004 were retrieved and reviewed. All patients (n=30) diagnosed with lymphomatous involvement of the breast were selected. Distinction between primary and secondary breast lymphomas was not made owing to lack of availability of clinical information. A total of 5637 breast malignancies were diagnosed in our department during the study period of 10 years and the total number of NHLs (Nodal and extra Nodal) was 2632. Thirty (n=30) patients accounting for 1.13% were diagnosed to have lymphomatous involvement of the breast. The Female to Male ratio was 13.5:1; age range was 12-92 years with a median age of 43 years (Mean age 46.5 years and Standard deviation of age was 16.88 years). The sites of the ...
Mutant alleles of TMPRSS3 are associated with nonsyndromic recessive deafness (DFNB8/B10). TMPRSS... more Mutant alleles of TMPRSS3 are associated with nonsyndromic recessive deafness (DFNB8/B10). TMPRSS3 encodes a predicted secreted serine protease, although the deduced amino acid sequence has no signal peptide. In this study, we searched for mutant alleles of TMPRSS3 in families from Pakistan and Newfoundland with recessive deafness co-segregating with DFNB8/B10 linked haplotypes and also more thoroughly characterized the genomic structure of TMPRSS3. We enrolled families segregating recessive hearing loss from Pakistan and Newfoundland. Microsatellite markers flanking the TMPRSS3 locus were used for linkage analysis. DNA samples from participating individuals were sequenced for TMPRSS3. The structure of TMPRSS3 was characterized bioinformatically and experimentally by sequencing novel cDNA clones of TMPRSS3. We identified mutations in TMPRSS3 in four Pakistani families with recessive, nonsyndromic congenital deafness. We also identified two recessive mutations, one of which is novel,...
Journal of community hospital internal medicine perspectives, 2014
Acquired adult-onset zinc deficiency is occasionally reported in patients with malnutrition state... more Acquired adult-onset zinc deficiency is occasionally reported in patients with malnutrition states, such as alcoholism, or malabsorptive states, such as post-bariatric surgery. The defining symptoms of hypozincemia include a classic triad of necrolytic dermatitis, diffuse alopecia, and diarrhea. We report a case of zinc deficiency in a 39-year-old man with history of gastric bypass surgery and alcoholism. For this patient, severe hypozincemia confirmed acrodermatitis, and zinc supplementation was met with gradual improvement.
2009 IEEE 13th International Multitopic Conference, 2009
Abstract A fractal monopole antenna based on the Sierpinski gasket is studied in this paper. The... more Abstract A fractal monopole antenna based on the Sierpinski gasket is studied in this paper. The monopole antenna based on the Sierpinski gasket constructed through three iterations displays a multiband behaviour with three bands that are log-periodically spaced by a ...
The reliability concept provides a means of incorporating some degree of certainty into the pavem... more The reliability concept provides a means of incorporating some degree of certainty into the pavement design process to ensure that the outcomes of the process will provide acceptable levels of service until the end of the intended design life. Pavement structural performance and rehabilitation design are highly dependent on the in situ layer properties. Pavement layer thickness is an essential input in backcalculation analysis performed with measured surface deflections to evaluate the in situ structural capacity of a pavement. Inaccurate thickness information may lead to significant errors in the backcalculated layer moduli and, hence, in the rehabilitation design. Because pavement layer thickness has some degree of variability (normal variability), it is important to consider this variability in the backcalculation analysis and rehabilitation design. A procedure was developed to implement the reliability concept in backcalculation analysis to account for the normal variability in layer thickness within structurally homogeneous sections. This procedure was developed on the basis of in situ layer information obtained from a ground-penetrating radar study performed for the New Jersey Department of Transportation. This paper provides an overview of the procedure, along with the results of the pilot implementation of the procedure. This reliability procedure complements the reliability factor of the 1993 AASHTO pavement design guide, as the latter reliability factor does not account for the in situ layer thickness.
Intravitreal inflammation, induced by either lens injury, or intravitreal injection of zymosan (I... more Intravitreal inflammation, induced by either lens injury, or intravitreal injection of zymosan (IVZ), protects RGC from apoptosis and stimulates axon regeneration after optic nerve transection. Here, we investigate the differential effects of intra-optic nerve zymosan (ONZ) and IVZ injections on RGC neuroprotection and axogenesis. After both IVZ and ONZ injection, zymosan-induced inflammation promoted a similar 4-/5-fold enhancement in RGC survival, compared to optic nerve transected controls, but only IVZ promoted RGC axon regeneration. IVZ was the most effective in activating retinal astrocyte/Müller cells while regulated intramembraneous proteolysis (RIP) of p75(NTR) and inactivation of Rho (key components of the axon growth inhibitory signalling cascade) occurred in both ONZ and IVZ, but only in the latter did RGC axons regenerate. We suggest that neuroprotective factors may be transported to RGC somata by retrograde transport after ONZ and diffuse into the retina after IVZ injection, but an axogenic agent is required to initiate and maintain disinhibited RGC axon regeneration that may be an exclusive property of a Müller cell-derived factor released after IVZ.
In the injured central nervous system (CNS), transforming growth factor (TGF)-β1/2-induced scarri... more In the injured central nervous system (CNS), transforming growth factor (TGF)-β1/2-induced scarring and wound cavitation impede axon regeneration implying that a combination of both scar suppression and axogenic treatments is required to achieve functional recovery. After treating acute and chronic dorsal funicular spinal cord lesions (DFL) in adult rats with the pan-TGF-β1/2 antagonist Decorin, we report that in: (1), acute DFL, the development of all injury parameters was significantly retarded e.g., wound cavity area by 68%, encapsulation of the wound by a glia limitans accessoria (GLA) by 65%, GLA basal lamina thickness by 94%, fibronectin, NG2 and Sema-3A deposition by 87%, 48% and 48%, respectively, and both macrophage and reactive microglia accumulations by 60%; and (2), chronic DFL, all the above parameters were attenuated to a lesser extent e.g., wound cavity area by 11%, GLA encapsulation by 25%, GLA basal lamina thickness by 31%, extracellular fibronectin, NG2 and Sema-3A deposition by 58%, 22% and 29%, respectively, and macrophage and reactive microglia accumulations by 44%. Moreover, in acute and chronic DFL, levels of tissue plasminogen activator (tPA) were raised (by 236% and 482%, respectively), as were active-MMP-2 (by 64% and 91%, respectively) and active-MMP-9 (by 122% and 18%, respectively), while plasminogen activator inhibitor-1 (PAI-1) was suppressed (by 56% and 23%, respectively) and active-TIMP-1 and active TIMP-2 were both lower but only significantly suppressed in acute DFL (by 56 and 21%, respectively). These findings demonstrate that both scar tissue mass and cavitation are attenuated in acute and chronic spinal cord wounds by Decorin treatment and suggest that the dominant effect of Decorin during acute scarring is anti-fibrogenic through suppression of inflammatory fibrosis by neutralisation of TGF-β1/2 whereas, in chronic lesions, Decorin-induction of tPA and MMP (concomitant with reduced complimentary levels of TIMP and PAI-1) leads to dissolution of the mature established scar by fibrolysis. Decorin also promoted the regeneration of similar numbers of axons through acute and chronic wounds. Accordingly, intrathecal delivery of Decorin offers a potential translatable treatment for scar tissue attenuation in patients with spinal cord injury.
... 3 Mixing speed effect with 3 mg/L of PAC at 40 and 400 rpm ... 50% of media leads to clogging... more ... 3 Mixing speed effect with 3 mg/L of PAC at 40 and 400 rpm ... 50% of media leads to clogging phenomena or a decrease in porosity because of accumulated suspended solids (SS) and ... In addition, the recycle of backwash solids did not affect the over-all treatment process on a ...
Usher syndrome (USH) is a hereditary disorder associated with sensorineural hearing impairment, p... more Usher syndrome (USH) is a hereditary disorder associated with sensorineural hearing impairment, progressive loss of vision attributable to retinitis pigmentosa and variable vestibular function. Three clinical types have been described with type I (USH1) being the most severe. To date six USH1 loci have been reported. We ascertained two large Pakistani consanguineous families segregating profound hearing loss, vestibular dysfunction, and retinitis pigmentosa, the defining features of USH1. In these families we excluded linkage of USH to the 11 known USH loci, and subsequently performed a genome-wide linkage screen. We found a novel USH1 locus designated USH1H that mapped to chromosome 15q22-23 in a 4.92 cM interval. This locus overlaps the non-syndromic deafness locus DFNB48 raising the possibility that the two disorders may be caused by allelic mutations.
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Papers by Zubair Ahmed