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V Zaman

Publications and source records attributed to V Zaman.

At least 19 recordsLinked to original sources

A partial GDNF depletion leads to earlier age-related deterioration of motor function and tyrosine hydroxylase expression in the substantia nigra.

Glial cell line-derived neurotrophic factor (GDNF) is a trophic factor for peripheral organs, spinal cord, and midbrain dopamine (DA) neurons. Levels of GDNF deteriorate in the substantia nigra in Parkinson's disease (PD). A heterozygous mouse model was created to assess whether chronic reductions in this neurotrophic factor impact motor function and the nigrostriatal dopamine system during the aging process. Due to the important role GDNF plays in kidney development, kidney function and histology were assessed and were found to be normal in both wild-type (WT) and GDNF+/- mice up to 22 months of age. Further, the animals of both genotypes had similar weights throughout the experiment. Locomotor activity was assessed for male WT and GDNF+/- mice at 4-month intervals from 4 to 20 months of age. Both GDNF+/- and WT mice exhibited an age-related decline in horizontal activity, although this was found 4 months earlier in GDNF+/- mice, at 12 months of age. Comparison of young (8 month old) and aged (20 month old) GDNF+/- and WT mice on an accelerating rotarod apparatus established a deficiency for aged but not young GDNF+/- mice, while aged WT mice performed as well as young WT mice on this task. Finally, both WT and GDNF+/- mice exhibited an age-related decrease in substantia nigra TH immunostaining, which was accelerated in the GDNF+/- mice. These behavioral and histological alterations suggest that GDNF may be an important factor for maintenance of motor coordination and spontaneous activity as well as DA neuronal function during aging, and further suggest that GDNF+/- mice may serve as a model for neuroprotective or rescue studies.

Age Factors↗

Incorporation of embryonic CA3 cell grafts into the adult hippocampus at 4-months after injury: effects of combined neurotrophic supplementation and caspase inhibition.

As receptivity of the injured hippocampus to cell grafts decreases with time after injury, strategies that improve graft integration are necessary for graft-mediated treatment of chronic neurodegenerative conditions such as temporal lobe epilepsy. We ascertained the efficacy of two distinct graft-augmentation strategies for improving the survival of embryonic day 19 hippocampal CA3 cell grafts placed into the adult hippocampus at 4-months after kainic acid induced injury. The donor cells were labeled with 5'-bromodeoxyuridine, and pre-treated and grafted with either brain-derived neurotrophic factor, neurotrophin-3 and a caspase inhibitor or fibroblast growth factor and caspase inhibitor. The yield of surviving grafted cells and neurons were quantified at 2-months post-grafting. The yield of surviving cells was substantially greater in grafts treated with brain-derived neurotrophic factor, neurotrophin-3 and caspase inhibitor (84%) or fibroblast growth factor and caspase inhibitor (99% of injected cells) than standard cell grafts (26%). Because approximately 85% of surviving grafted cells were neurons, increased yield in augmented groups reflects enhanced survival of grafted neurons. Evaluation of the mossy fiber synaptic re-organization in additional kainic acid-lesioned rats receiving grafts enriched with brain-derived neurotrophic factor, neurotrophin-3 and caspase inhibitor at 3-months post-grafting revealed reduced aberrant dentate mossy fiber sprouting in the dentate supragranular layer than "lesion-only" rats at 4 months post-kainic acid, suggesting that some of the aberrantly sprouted mossy fibers in the dentate supragranular layer withdraw when apt target cells (i.e. grafted neurons) become available in their vicinity. Thus, the yield of surviving neurons from CA3 cell grafts placed into the adult hippocampus at an extended time-point after injury could be enhanced through apt neurotrophic supplementation and caspase inhibition. Apt grafting is also efficacious for reversing some of the abnormal synaptic reorganization prevalent in the hippocampus at later time-points after injury.

Animals↗

Glial cell line-derived neurotrophic factor is essential for neuronal survival in the locus coeruleus-hippocampal noradrenergic pathway.

It has been shown that the noradrenergic (NE) locus coeruleus (LC)-hippocampal pathway plays an important role in learning and memory processing, and that the development of this transmitter pathway is influenced by neurotrophic factors. Although some of these factors have been discovered, the regulatory mechanisms for this developmental event have not been fully elucidated. Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor influencing LC-NE neurons. We have utilized a GDNF knockout animal model to explore its function on the LC-NE transmitter system during development, particularly with respect to target innervation. By transplanting various combinations of brainstem (including LC) and hippocampal tissues from wildtype or GDNF knockout fetuses into the brains of adult wildtype mice, we demonstrate that normal postnatal development of brainstem LC-NE neurons is disrupted as a result of the GDNF null mutation. Tyrosine hydroxylase immunohistochemistry revealed that brainstem grafts had markedly reduced number and size of LC neurons in transplants from knockout fetuses. NE fiber innervation into the hippocampal co-transplant from an adjacent brainstem graft was also influenced by the presence of GDNF, with a significantly more robust innervation observed in transplants from wildtype fetuses. The most successful LC/hippocampal co-grafts were generated from fetuses expressing the wildtype GDNF background, whereas the most severely affected transplants were derived from double transplants from null-mutated fetuses. Our data suggest that development of the NE LC-hippocampal pathway is dependent on the presence of GDNF, most likely through a target-derived neurotrophic function.

Animals↗

The noradrenergic system of aged GDNF heterozygous mice.

Glial cell line-derived neurotrophic factor (GDNF) is a trophic factor for noradrenergic (NE) neurons of the pontine nucleus locus coeruleus (LC). Decreased function of the LC-NE neurons has been found during normal aging and in neurodegenerative disorders. We have previously shown that GDNF participates in the differentiation of LC-NE neurons during development. However, the continued role of GDNF for LC-NE neurons during maturation and aging has not been addressed. We examined alterations in aged mice that were heterozygous for the GDNF gene (Gdnf+/-). Wild-type (Gdnf+/+) and Gdnf+/- mice (18 months old) were tested for locomotor activity and brain tissues were collected for measuring norepinephrine levels and uptake, as well as for morphological analysis. Spontaneous locomotion was reduced in Gdnf+/- mice in comparison with Gdnf+/+ mice. The reduced locomotor activity of Gdnf+/- mice was accompanied by reductions in NE transporter activity in the cerebellum and brain stem as well as decreased norepinephrine tissue levels in the LC. Tyrosine hydroxylase (TH) immunostaining demonstrated morphological alterations of LC-NE cell bodies and abnormal TH-positive fibers in the hippocampus, cerebellum, and frontal cortex of Gdnf+/- mice. These findings suggest that the LC-NE system of Gdnf+/- mice is impaired and suggest that GDNF plays an important role in continued maintenance of this neuronal system throughout life.

Aging↗

Combined neurotrophic supplementation and caspase inhibition enhances survival of fetal hippocampal CA3 cell grafts in lesioned CA3 region of the aging hippocampus.

Fetal hippocampal CA3 cells show excellent survival when homotopically grafted into the kainic acid-lesioned CA3 region of the young adult hippocampus, a model of temporal lobe epilepsy. However, survival of these cells in the kainic acid-lesioned CA3 region of the aging hippocampus is unknown. We hypothesize that fetal CA3 grafts into the lesioned CA3 region of the middle-aged and aged hippocampus exhibit significantly diminished cell survival compared with similar grafts in the lesioned young adult hippocampus unless pre-treated and transplanted with factors that augment graft cell survival. We analyzed cell survival of 5'-bromodeoxyuridine-labeled embryonic day 19 CA3 grafts following their transplantation into the lesioned CA3 region of the middle-aged and aged rat hippocampus. Grafts were placed 4 days after an i.c.v. administration of kainic acid, and absolute cell survival of grafts was quantified 1 month after grafting using 5'-bromodeoxyuridine immunostaining of serial sections and the optical fractionator counting method. Grafts into both middle-aged and aged hippocampus exhibited analogous but significantly diminished cell survival (30% of injected cells) compared with similar grafts into the young adult hippocampus (72% cell survival). However, the extent of cell survival of CA3 grafts pre-treated and transplanted with a combination of neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 and the caspase inhibitor acetyl-tyrosinyl-valyl-alanyl-aspartyl-chloro-methylketone was significantly enhanced in both middle-aged and aged hippocampus (51-63% cell survival). These results underscore that aging impairs the conduciveness of the CA3 region for robust survival of homotopic fetal CA3 grafts after lesion. However, a combined neurotrophic supplementation and caspase inhibition significantly enhances survival of fetal CA3 cells in the lesioned aging hippocampus. Thus, pre-treatment and grafting of donor cells with a combination of factors that support growth of specific donor cells may considerably enhance survival and integration of fetal grafts into the lesioned aging CNS in clinical trials.

Aging↗

Fetal hippocampal CA3 cell grafts transplanted to lesioned CA3 region of the adult hippocampus exhibit long-term survival in a rat model of temporal lobe epilepsy.

Intracerebroventricular administration of kainic acid in the adult rat, a widely used model for studying human temporal lobe epilepsy, results in widespread degeneration of CA3-pyramidal neurons. Transplantation of specific fetal hippocampal CA3 cell grafts into the lesioned CA3-region at a prolonged post lesion delay of 45-day leads to 31% graft cell survival at 1 month postgrafting and significantly facilitates appropriate recovery of the lesioned host hippocampus. However, the capability of hippocampal CA3 cell grafts for enduring survival in this model is unknown. We hypothesize that a significant fraction of fetal CA3 cells grafted into the lesioned CA3 region of the adult hippocampus at 45-days postlesion exhibit long-term survival. We measured the extent of cell survival within 5'-bromodeoxyuridine-labeled CA3 cell grafts at 1 year postgrafting, following their transplantation at 45 days postlesion into the lesioned CA3-region. Quantification of absolute graft cell survival using BrdU immunostaining and the optical fractionator counting method revealed survival of 36% of grafted cells at 1 year postgrafting. Thus, over a third of fetal hippocampal CA3 cells transplanted to the lesioned CA3-region at 45 days postlesion exhibit long-term survival. Further, the extent of cell survival in these grafts is highly analogous to the degree of cell survival in CA3 grafts analyzed earlier at 1 month postgrafting, suggesting that specific fetal cells that survive the first month of grafting into the lesioned CNS area are capable of exhibiting enduring survival.

Aging↗

Tropical pulmonary eosinophilia and filariasis in Pakistan.

Filariasis is a major health problem in South Asia, particularly India, Sri Lanka and Bangladesh. Pakistan was presumed to be not affected. We report for the first time confirmed cases of tropical pulmonary eosinophilia (TPE) in indigenous patients as a result of infection with Wuchereria bancrofti. Following clinical examination, total leukocyte and eosinophil counts were recorded. Parasitological examinations included blood for microfilariae and stool and urine for eggs of intestinal parasites. Total immunoglobulin (Ig) E and specific antifilarial IgG were measured. Suspected cases of TPE were treated with diethylcarbamazine, 6 mg/kg for four weeks and were followed up to 2 and 4 weeks after treatment. Four persons fulfilled the criteria for TPE. Their response to treatment was marked with clinical improvement, reduction in eosinophil count and reduced titers of specific antifilarial antibodies. Two persons had W. bancrofti antigen in their sera confirmed by filariasis antigen detection test. Tropical pulmonary eosinophilia due to Wuchereria. bancrofti, although rare, is present in Pakistan.

Adolescent↗

Survival of grafted fetal neural cells in kainic acid lesioned CA3 region of adult hippocampus depends upon cell specificity.

We hypothesize that the degree of graft cell survival within the damaged CNS correlates with the specificity of donor cells to the region of grafting. We investigated graft cell survival following transplantation of fetal micrografts into the CA3 region of the adult rat hippocampus at a time-point of 4 days after an intracerebroventricular administration of kainic acid (KA). Grafts consisted of 5'-bromodeoxyuridine (BrdU) labeled embryonic day (E) 19 cells from hippocampal fields CA3 and CA1 and E15 and E19 cells from the striatum. Absolute cell survival in these grafts was quantitatively analyzed at 1 month postgrafting, using BrdU immunostaining of serial sections and three-dimensional reconstruction of grafts. Absolute graft cell survival in lesioned CA3 was dramatically greater for cells having hippocampal origin (CA3 cells, 69% cell survival; CA1 cells, 42% cell survival) than those having nonhippocampal origin, such as striatal cells (E15 cells, 12% cell survival; E19 cells, 4% cell survival). This difference is in sharp contrast to survival of these cells in culture, where E19 cells from both hippocampal and nonhippocampal origins exhibited similar survival. Comparison of survival among hippocampal cell types indicated significantly greater survival for cells that are specific to the lesioned area (i.e., CA3 cells) than for those that are nonspecific to the lesioned area (i.e., CA1 cells). Graft cell survival in the intact CA3 region (contralateral to KA administration), however, did not differ either between cells having hippocampal and nonhippocampal origins or between CA3 and CA1 cells (CA3 cells, 26% cell survival; CA1 cells, 33% cell survival; and E15 striatal cells, 20% cell survival). These results underscore the finding that enhanced survival of fetal cell grafts in the lesioned CNS is critically dependent upon the specificity of donor fetal cells to the region of transplantation. Thus, grafting of cells that are specific to the lesioned area is a prerequisite for achieving maximal graft cell survival and integration in the lesioned host CNS.

Animals↗

Direct amplification of Entamoeba histolytica DNA from amoebic liver abscess pus using polymerase chain reaction.

An important and serious complication of intestinal infection with Entamoeba histolytica is the involvement of the liver (hepatic amoebiasis). Hepatic amoebiasis is usually diagnosed by the clinical picture (pain in the right upper quadrant and fever), ultrasound examination and positive serology. However, none of these tests are definitive and the picture overlaps with pyogenic liver abscess caused by bacteria. It is for this reason that the feasibility of using polymerase chain reaction (PCR) for the detection of E. histolytica DNA in liver abscess pus was investigated. A comparative study was done to verify the sensitivity of ten pairs of primers specific for detecting E. histolytica in stools. Samples of liver abscess pus from 22 serology-positive patients were collected under ultrasound guidance; and these were used directly in PCR assays without any prior pre-treatment of the samples. Of the ten pairs of previously published primers tested, two pairs of primers (PI + P2 and P11 + P12) were found to give 100% sensitivity. Based on these results, we recommend that PCR assay can be successfully used to confirm the diagnosis of amoebic liver abscess with the primers identified.

Animals↗

Ultrastructure of the Endolimax nana cyst.

This is the first report on the ultrastructure of the Endolimax nana cyst. These cysts are mostly ovoid in shape and have a distinct cyst wall measuring 80 nm. The nuclear membrane is without pores or associated chromatin deposits. The cytoplasm does not have mitochondria or a Golgi apparatus but shows elongated tubular structures made up of a double row of ribosome-like particles. The nature and function of this structure is not known, but it appears to be characteristic of this species and has not been reported from any other intestinal ameba.

Amebiasis↗

Scanning electron microscopy of Chilomastix mesnili (Wenyon 1910) Alexieieff, 1912.

Scanning electron microscopy of Chilomastix mesnili shows that the cysts are lemon-shaped with one end broadly rounded and the other conical. The trophozoite has five flagella coming out of the anterior end. Four of these are free and the fifth is attached to the body by an undulating membrane. The undulating membrane extends along the whole length of the body of the parasite with the exception of the tail. The tail is an elongated structure almost equal in length to the main body of the parasite.

Animals↗

Pattern of long-distance projections from fetal hippocampal field CA3 and CA1 cell grafts in lesioned CA3 of adult hippocampus follows intrinsic character of respective donor cells.

Fetal hippocampal grafts transplanted to the lesioned CA3 of adult hippocampus can extend axonal projections to many regions of the host brain. However, the identity of grafted cells that project to specific host regions is unknown. We hypothesize that the pattern of long-distance axonal projections from distinct fetal hippocampal cells grafted to lesioned CA3 is specified by the intrinsic nature of respective donor cells rather than characteristics of the host graft region. We grafted fetal hippocampal CA3 or CA1 cells into kainic acid lesioned CA3 of adult hippocampus at four days post-lesion. Neurons projecting to either the contralateral hippocampus or the ipsilateral septum were then measured in these grafts at four months post-grafting using Fluoro-Gold and DiI tract tracing. CA3 grafts located close to the degenerated CA3 cell layer showed a high propensity for establishing projections into the contralateral hippocampus (commissural projections) compared to similarly located CA1 grafts, which exhibited negligible commissural projections. Similar distinction was observed between the two graft types even when they were located only partially in the lesioned CA3. Among CA3 grafts, those placed near the degenerated CA3 cell layer established significantly greater commissural projections than those placed only partially in the CA3 region. Septal projections, in contrast, were robust from both CA3 and CA1 grafts. This differential projection pattern between CA3 and CA1 grafts resembles projections of CA3 and CA1 cells in intact hippocampus.These results demonstrate that the intrinsic character of grafted fetal cells determines the type of efferent projections from fetal grafts into different targets in the lesioned adult host brain. However, the extent of efferent projections from specific grafts is also influenced by the location of grafted cells within the host region. Thus, graft-mediated appropriate reconstruction of damaged circuitry in the lesioned brain may require grafting of homotopic donor cells. Further, the robust and specific projections observed from CA3 grafts is likely beneficial for functional recovery of hippocampus following CA3 injury and hence of significance towards developing a graft-mediated therapy for human temporal lobe epilepsy.

Animals↗

Postcystic development of Blastocystis hominis.

A concentrated suspension of Blastocystis hominis cysts was inoculated into Jones' medium and removed after 24 h for study of their development at the ultrastructural level. The parasite divides in the cyst, and up to three daughter cells can be seen. During this process the cyst wall dissolves, leaving behind thin membranous remnants. Excystation occurs mostly by the emergence of the daughter cells through an aperture in the outer fibrillar coat. Before excystation the vacuolar and the granular stages form and the daughter cells develop their own fibrillar layer.

Animals↗

Scanning electron microscopy of the surface coat of Blastocystis hominis.

Scanning electron microscopy of Blastocystis hominis showed that its outer coat has a fibrillar structure and individual fibrils may extend up to 5 microm from the periphery of the parasite. The surface coat remains intact during cell division. Bacteria are often seen adhering to it, but for the first time a trophozoite of Chilomastix mesnili was also seen in this position. It is postulated that breakdown of attached organisms may provide nutrients for Blastocystis.

Animals↗

Ultrastructure of the nucleus of the Iodamoeba bütschlii cyst.

The ultrastructure of the Iodamoeba bütschlii cyst from human feces was studied. The glycogen mass appears as a compact dense body in the cytoplasm without any surrounding membrane. The cytoplasm has no mitochondrion. The nucleus shows a distinct nucleolus filled with electron-dense particles. On one side of the nucleolus are electron-dense cytoplasmic masses measuring 200-400 nm. The nuclear membrane is two-layered and shows pores.

Amebiasis↗

Scanning electron microscopy of Blastocystis hominis cysts.

Scanning electron microscopy of Blastocystis hominis cysts reveals that some cysts have an outer coat, whereas others are naked. If intact, the outer coat forms a fan-like structure around the cyst and its surface is granular. The fragmented outer coat adheres to other cysts and bacteria, forming irregular clumps.

Animals↗