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Biomedical subjects

B Dass

Publications and source records attributed to B Dass.

At least 19 recordsLinked to original sources
PubMed2004

Sonic hedgehog delivered by an adeno-associated virus protects dopaminergic neurones against 6-OHDA toxicity in the rat.

Direct intracerebral administration of sonic hedgehog (SHH) reduces 6-OHDA and MPTP toxicity to nigral dopaminergic cells in rats and primates. To determine whether transfection of the DNA sequence for SHH using viral vectors also protects against 6-OHDA toxicity, a type 2 adeno- associated virus (AAV) incorporating 600 base pairs of N-terminal SHH DNA was generated to induce SHH expression in rat striatum.AAV-SHH was injected into the striatum, 3 weeks prior to the initiation of an unilateral partial 6-OHDA nigro-striatal lesion. Animals receiving 4x10(7) viral particles of AAV-SHH showed a reduction in (+)-amphetamine induced ipsilateral turning over 4 weeks, when compared to animals receiving vehicle or a LacZ encoding vector. Following vehicle or AAV-LacZ administration, 6-OHDA caused a marked loss of striatal dopamine content and nigral tyrosine hydroxylase (TH) immunopositive cells. Following treatment with 4x10(7) viral particles of AAV-SHH the loss of striatal dopamine content was reduced and there was marked preservation of nigral dopaminergic cells. However, administration of 4x10(8) particles of AAV-SHH did not cause a significant change in (+)-amphetamine-induced rotation, striatal dopamine levels or the number of nigral TH immunoreactive cells following 6-OHDA lesioning compared to vehicle or AAV-LacZ treated animals. The results show that SHH delivered via a viral vector can protect dopaminergic neurons against 6-OHDA toxicity and suggest that this could be developed into a novel treatment for PD. However, the effects maybe dose limited due to uncoupling of hedgehog receptor signalling at higher levels of SHH expression.

Adenoviridae↗
PubMed2002

6-Hydroxydopamine lesioning differentially affects alpha-synuclein mRNA expression in the nucleus accumbens, striatum and substantia nigra of adult rats.

The effect of a unilateral 6-hydroxydopamine (6-OHDA) lesion and/or repeated administration of levodopa (L-DOPA) to normal and 6-OHDA-lesioned rats on alpha-synuclein mRNA expression was investigated by in situ hybridization histochemistry. A 6-OHDA lesion of the nigro-striatal pathway alone, confirmed by the loss of nigral tyrosine hydroxylase mRNA expression, markedly decreased alpha-synuclein mRNA in the lesioned substantia nigra (SN). In contrast, the levels of alpha-synuclein mRNA in the denervated striatum and nucleus accumbens were not altered. Chronic administration of L-DOPA to normal or 6-OHDA-lesioned rats had no effect on alpha-synuclein mRNA expression in the SN, striatum or nucleus accumbens. These data confirm that alpha-synuclein is localized in the nigro-striatal tract but that its gene expression is not regulated by dopamine.

Animals↗
PubMed2002

Behavioural and immunohistochemical changes following supranigral administration of sonic hedgehog in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmosets.

Sonic hedgehog (SHH) has trophic actions on dopaminergic cell cultures and protects them from MPP(+) toxicity but its in vivo actions have not been explored. We now investigate the effects of unilateral supranigral administration of SHH on nigro-striatal function in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmosets. SHH (0.1 or 1.0 microg) or vehicle was stereotaxically injected into the region of the right substantia nigra twice with an interval of 5 weeks between administrations. The first or second administration of low dose SHH (0.1 microg) did not significantly improve motor disability or locomotor activity compared to time-matched vehicle-treated animals. There was, however, an approximately 30% improvement in both motor disability and locomotor activity following the first administration of high dose SHH (1.0 microg). No further improvements occurred following the second high dose SHH treatment. Acute oral administration of L-3,4-dihydroxyphenylalanine (L-DOPA) produced a smaller increase in locomotor activity and greater reversal of motor disability in animals treated with SHH than occurred in vehicle-treated common marmosets. In the substantia nigra pars compacta, ipsilateral to SHH administration, the number of tyrosine hydroxylase-positive neurones was increased by 21% (P > 0.05) and 57% (P < 0.05) in low and high dose SHH groups respectively compared to the untreated contralateral hemisphere. There was no difference in the number of glial fibrillary acidic protein-positive cells. SHH may improve nigro-striatal function by restoring tyrosine hydroxylase positivity. This is reflected by an improvement in basal disability and a reduction in the lesion-induced response to L-DOPA.

Animals↗
PubMed2002

Tuberculosis of the spine (Pott's disease) presenting as 'compression fractures'.

STUDY DESIGN: Case reports and survey of literature. OBJECTIVE: Case reports of two women with tuberculosis (TB) of the spine (Pott's disease) presenting with severe back pain and diagnosed as compression fracture are described. Physicians should include Pott's disease in the differential diagnosis when patients present with severe back pain and evidence of vertebral collapse. SETTING: Ohio, USA METHODS: A review of the literature on the pathogenesis, pathophysiology, clinical presentation, diagnostic methods, treatment and prognosis of spinal TB was conducted. RESULTS: After initial delay, proper diagnosis of spinal TB was made in our patients. Microbiologic diagnosis confirmed M. tuberculosis, and appropriate medical treatment was initiated. CONCLUSIONS: Although uncommon, spinal TB still occurs in patients from developed countries, such as the US and Europe. Back pain is an important symptom. Vertebral collapse from TB may be misinterpreted as 'compression fractures' especially in elderly women. Magnetic resonance imaging scan (MRI) is an excellent procedure for the diagnosis of TB spine. However, microbiologic diagnosis is essential. Mycobacterium tuberculosis may be cultured from other sites. Otherwise, biopsy of the spine lesion should be done for pathologic diagnosis, culture and stain for M. tuberculosis. Clinicians should consider Pott's disease in the differential diagnosis of patients with back pain and destructive vertebral lesions. Proper diagnosis and anti-tuberculosis treatment with or without surgery will result in cure.

Aged↗
PubMed2001

Overexpression of the CstF-64 and CPSF-160 polyadenylation protein messenger RNAs in mouse male germ cells.

Messenger RNAs for several components of the transcriptional apparatus are greatly overexpressed in postmeiotic male germ cells in rodents (Schmidt and Schibler, Development 1995; 121:2373-2383). Because of the tight coupling of polyadenylation and transcription, we examined expression in germ cells of mRNAs for key polyadenylation factors. The mRNA for the 64 000 M(r) subunit of the cleavage stimulation factor (CstF-64) was expressed at least 250-fold greater in mouse testicular RNA than in liver RNA. RNA blot analysis showed that the mRNA for the 160 000 M(r) subunit of the cleavage and polyadenylation specificity factor was similarly overexpressed, as was the mRNA for the large subunit of RNA polymerase II. General transcription factors, such as the TATA-binding protein and transcription factor IIH, and splicing factors, such as components of the small nuclear ribonucleoproteins, were also expressed in meiotic and postmeiotic germ cells. The X-linked CstF-64 protein is expressed before and after but not during meiosis in the mouse (Wallace et al., Proc Natl Acad Sci U S A 1999; 96:6763-6768), which suggests that overexpression of mRNA transcription and processing factors plays an essential role in postmeiotic germ cell mRNA metabolism.

Adenosine↗
PubMed2001

How important is history of unconsciousness in head injury patients?

A total of 100 patients of head injury were studied. They all underwent thorough clinical and neurological examination, skull radiography and CT scan of head. And with the help of all these parameters an evaluation was done to find out the importance of history of unconsciousness on risk of intracranial complications. A lot of controversies exist about detection of factors that make a patient of head injury a high risk candidate for developing intracranial complications. Young active population was the most commonly affected group in head injury with male preponderance at all ages. Roadside accident found to be the main cause of head trauma in adults while fall from height in paediatric age group. Although Glassgow Coma Index (GCI) was found to be a good predictor for intracranial complications as well as final outcome in patients with total score of 12 or less but it was not equally good in patients of minor head injury (GCI = 13-15). Similarly history of unconsciousness was not found to be correlating well with risk of intracranial complications but longer duration of unconsciousness was found to be a poor prognostic index.

Adult↗
PubMed2001

Transitional cell carcinoma manifesting as acute cor pulmonale: cause of microscopic tumor embolism.

Acute cor pulmonale is an uncommon manifestation of microscopic pulmonary tumor embolism. We describe the case of an 84-year-old man with a history of transitional cell carcinoma (TCC) of the urinary bladder who had acute cor pulmonale and died within a few hours after the onset of dyspnea. Autopsy showed that the right ventricle was dilated without hypertrophy. Microscopic examination of the lung showed that the small arteries, arterioles, and capillaries were filled with micrometastases of TCC. Microscopic pulmonary tumor embolism has rarely been reported with TCC, and to the best of our knowledge, such a fulminant course has not been previously described in the English language.

Acute Disease↗
PubMed2000

The gene for a variant form of the polyadenylation protein CstF-64 is on chromosome 19 and is expressed in pachytene spermatocytes in mice.

Many mRNAs in male germ cells lack the canonical AAUAAA but are normally polyadenylated (Wallace, A. M., Dass, B., Ravnik, S. E., Tonk, V., Jenkins, N. A., Gilbert, D. J., Copeland, N. G., and MacDonald, C. C. (1999) Proc. Natl. Acad Sci. U. S. A. 96, 6763-6768). Previously, we demonstrated the presence of two distinct forms of the M(r) 64,000 protein of the cleavage stimulation factor (CstF-64) in mouse male germ cells and in brain, a somatic M(r) 64,000 form and a variant M(r) 70,000 form. The variant form was specific to meiotic and postmeiotic germ cells. We localized the gene for the somatic CstF-64 to the X chromosome, which would be inactivated during male meiosis. This suggested that the variant CstF-64 was an autosomal homolog activated during that time. We have named the variant form "tau CstF-64," and we describe here the cloning and characterization of the mouse tauCstF-64 cDNA, which maps to chromosome 19. The mouse tauCstF-64 protein fits the criteria of the variant CstF-64, including antibody reactivity, size, germ cell expression, and a common proteolytic digest pattern with tauCstF-64 from testis. Features of mtauCstF-64 that might allow it to promote the germ cell pattern of polyadenylation include a Pro --> Ser substitution in the RNA-binding domain and significant changes in the region that interacts with CstF-77.

Amino Acid Sequence↗
PubMed1999

Chronic L-DOPA treatment increases striatal cannabinoid CB1 receptor mRNA expression in 6-hydroxydopamine-lesioned rats.

The effect of a unilateral 6-hydroxydopamine (6-OHDA) lesion of the left medial forebrain bundle and 3 weeks treatment with L-DOPA of normal and 6-OHDA lesioned rats on CB1r mRNA expression was investigated by in situ hybridization. A 6-OHDA lesion of nigrostriatal pathway alone, confirmed by the loss of nigral tyrosine hydroxylase mRNA, did not alter CB1r mRNA levels in the dopamine depleted striatum. Similarly, chronic L-DOPA treatment of normal rats had no effect on striatal CB1r mRNA expression. In contrast, chronic L-DOPA treatment of 6-OHDA-lesioned rats significantly increased CB1r mRNA expression in the denervated striatum. These results suggest that the CB1r activity may be altered by L-DOPA's action and this may be related to the treatment of Parkinson's disease.

Adrenergic Agents↗
PubMed1999

Two distinct forms of the 64,000 Mr protein of the cleavage stimulation factor are expressed in mouse male germ cells.

Polyadenylation in male germ cells differs from that in somatic cells. Many germ cell mRNAs do not contain the canonical AAUAAA in their 3' ends but are efficiently polyadenylated. To determine whether the 64,000 Mr protein of the cleavage stimulation factor (CstF-64) is altered in male germ cells, we examined its expression in mouse testis. In addition to the 64,000 Mr form, we found a related approximately 70,000 Mr protein that is abundant in testis, at low levels in brain, and undetectable in all other tissues examined. Expression of the approximately 70,000 Mr CstF-64 was limited to meiotic spermatocytes and postmeiotic spermatids in testis. In contrast, the 64,000 Mr form was absent from spermatocytes, suggesting that the testis-specific CstF-64 might control expression of meiosis-specific genes. To determine why the 64,000 Mr CstF-64 is not expressed in spermatocytes, we mapped its chromosomal location to the X chromosome in both mouse and human. CstF-64 may, therefore, be absent in spermatocytes because the X chromosome is inactivated during male meiosis. By extension, the testis-specific CstF-64 may be expressed from an autosomal homolog of the X chromosomal gene.

Animals↗
PubMed1999

Quantification of the expression of a temperature-sensitive pigment allele in sailfin mollies (Poecilia latipinna) by image analysis.

Image analysis was used to quantify the activity of a temperature-sensitive macromelanophore-determining allele in sailfin mollies as the percentage of the body surface area covered by macromelanophores. Fish heterozygous for the macromelanophore-determining allele produced very few macromelanophores when raised at either 25 or 28 degrees C, even after more than 200 days. In contrast, the mean percent coverage for genetically identical fish raised at 22 degrees C increased steadily throughout the course of the experiment. Production of macromelanophores was sex influenced, with greater expressivity seen in males. At 22 degrees C, the mean percent coverages had significantly diverged between males and females by the age of 201 days. From that point on, the percent macromelanophore coverage of the males was consistently significantly higher than that of the females. The tendency to produce greater melanization at cooler temperatures is not the result of a heat-sensitive tyrosinase enzyme, as is the case in mammals carrying the Himalayan allele. In mollies, the activity of tyrosinase increases between 22 and 29 degrees C. We hypothesize that production of macromelanophores is under the control of a proto-oncogene.

Alleles↗
PubMed1998

Multiple diverticula of gall bladder.

Diverticula of the gall bladder are of no clinical significance unless associated with stones. Isolated location on Hartmann's pouch, body or neck have been explained on disordered embryogenesis but diffuse location all over the gall bladder is difficult to explain. We report a patient in whom multiple gall bladder diverticula were associated with a stone in the common bile duct.

Adult↗
PubMed1990

In vivo ultraviolet-exposed human epidermal cells activate T suppressor cell pathways that involve CD4+CD45RA+ suppressor-inducer T cells.

In vivo UV exposure of human epidermis abrogates the function of CD1+DR+ Langerhans cells and induces the appearance of CD1-DR+ Ag-presenting macrophages. Epidermal cells from UV-exposed skin, in contrast to epidermal cells from normal skin, potently activate autologous CD4+ T cells, and, in particular, the CD45RA+ (2H4+) (suppressor-inducer) subset. We therefore determined whether UV-exposure in humans leads to a T cell response in which suppression dominates. Autologous blood T cells were incubated with epidermal cell suspensions from in vivo UV-irradiated skin. After activation, repurified T cells were transferred in graded numbers to autologous mononuclear cells (MNC) stimulated with PWM and the resultant IgG production analyzed by ELISA. Relative to T cells activated by unirradiated control epidermal cells, T cells activated by UV-exposed epidermal cells demonstrated enhanced capacity to suppress IgG production (n = 6; p less than or equal to 0.03). Within the T cell population, CD8+ cells stimulated by UV-exposed epidermal cells could be directly activated to suppress PWM-stimulated MNC Ig production if IL-2 was provided in the reaction mixture. The suppressive activity was also transferable with purified CD4+ T cells stimulated by UV-exposed epidermal cells (n = 10; p less than or equal to 0.01), and was radiosensitive. Suppression was decreased when PWM-stimulated MNC were depleted of CD8+ T cells before mixing with CD4+ T cells activated by UV-exposed epidermal cells, suggesting indirect induction of CD8+ Ts cells contained within the responding MNC populations. Indeed, physical depletion of CD45RA+ cells resulted in total abrogation of the suppressor function contained in the CD4+ T cells. Activation of suppressor function was critically dependent on DR+ APC contained in UV-exposed epidermis. The data suggest that UV-exposure modulates cutaneous APC activity in humans, as in mice, such that the dominant immune response is tilted toward suppression. These mechanisms in normal individuals may function to dampen responses to UV-induced endogenous Ag that are pathogenic in autoimmune disorders. However, these mechanisms might also facilitate the growth of UV-induced skin cancers.

Antibody Formation↗
PubMed1990

Effects of cytochalasin D on actin and vinculin in cultured corneal epithelial cells.

Migrating corneal epithelial cells in culture elaborate lush arrays of actin filament bundles (stress fibers) which terminate peripherally at discrete cell-to-substratum adhesion complexes. These complexes contain several specific adhesion plaque proteins, of which vinculin is one. Vinculin, a 130 kD protein, putatively links the intracellular actin bundles in a transmembrane fashion (via integrin, a specific plasmalemmal junction protein) to focal attachment sites onto the underlying extracellular matrix substratum. Migrating rat corneal epithelial cells in tissue culture are treated with 0.1-1.0 microgram/ml cytochalasin D, an inhibitor of actin polymerization. This resulted in a generalized disruption of stress fibers, causing actin to the diffusely redistributed into discrete, round patches. Most, but not all, of these patches of actin appeared to colocalize with foci of vinculin. The focal patches of vinculin appeared to be larger and more diffuse in the cytochalasin-treated cells compared to the drug-free cells. These cytochalasin-induced cytoskeletal changes were associated with total cessation of cell migration and increased cellular detachment from the substratum.

Actins↗
PubMed1988

Distribution of cytoplasmic microtubules in migrating corneal epithelial cells. An immunofluorescence study.

Microtubules constitute one of the three components of the cellular skeleton (cytoskeleton) and have been implicated in the control of cell polarity, shape, intracellular transport, directional cell motility, and mitosis. With specific antibodies against tubulin, the principal microtubular protein, the cytoplasmic distribution of microtubules was demonstrated in tissue-cultured rat corneal epithelium. This was compared with the distribution of actin, another component of the cytoskeleton. Microtubules are essential for the late phase of corneal epithelial wound healing, characterized mainly by cell mitosis. As yet, little is known about their function in the nonmitotic early phase of healing, but possibilities include the maintenance of cell shape and intracellular transport.

Actins↗