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Biomedical subjects

S Sinha

Publications and source records attributed to S Sinha.

At least 199 records · Page 11Linked to original sources
PubMed2000

How study of respiratory physiology aided our understanding of abnormal brain function in panic disorder.

There is a substantial body of literature demonstrating that stimulation of respiration (hyperventilation) is a common event in panic disorder patients during panic attack episodes. Further, a number of abnormalities in respiration, such as enhanced CO2 sensitivity, have been detected in panic patients. This led some to posit that there is a fundamental abnormality in the physiological mechanisms that control breathing in panic disorder and that this abnormality is central to illness etiology. More recently, however, evidence has accumulated suggesting that respiratory physiology is normal in panic patients and that their tendency to hyperventilate and to react with panic to respiratory stimulants like CO2 represents the triggering of a hypersensitive fear network. The fear network anatomy is taken from preclinical studies that have identified the brain pathways that subserve the acquisition and maintenance of conditioned fear. Included are the amygdala and its brain stem projections, the hippocampus, and the medial prefrontal cortex. Although attempts to image this system in patients during panic attacks have been difficult, the theory that the fear network is operative and hyperactive in panic patients explains why both medication and psychosocial therapies are clearly effective. Studies of respiration in panic disorder are an excellent example of the way in which peripheral markers have guided researchers in developing a more complete picture of the neural events that occur in psychopathological states.

Arousal↗
PubMed2000

Extensive intra-tumor heterogeneity in primary human glial tumors as a result of locus non-specific genomic alterations.

Genomic changes are a hallmark of the neoplastic process. These range from alterations at specific loci and defined karyotypic changes which influence tumor behavior to generalized alterations exemplified by microsatellite instability. Generalized genomic changes within a tumor would be evidence in favor of the mutator hypothesis which postulates a role for such extensive changes during tumorigenesis. In this report, we have used the DNA fingerprinting technique of randomly amplified polymorphic DNA (RAPD) analysis to study genomic alterations within primary human astrocytic tumors (gliomas) in a locus non-specific manner. The RAPD fingerprinting profile of consecutive segments of tumors 2 mm across was studied; 17 astrocytic (high- and low-grade) tumors were sectioned end to end. Tissue from 50 consecutive sections, 40 microm thick (total 2 mm across), was pooled and taken to be a tumor compartment. DNA was subjected to RAPD amplification by 15 random 10-mer primers. A tumor segment was taken to have a DNA fingerprinting pattern different from others in the same specimen when its RAPD profile differed from others by at least one band of one RAPD reaction. All but one of the tumors showed compartments with a unique genetic profile, indicating genomic instability leading to widespread intra-tumor genetic heterogeneity. Eight tumors were also studied for loss of heterozygosity (LOH) of the p53 and D17S379 loci in the different segments as examples of alteration of specific tumor influencing loci. Three showed LOH of p53, which was limited to only one compartment of each tumor. The extensive intra-tumor genetic instability detected in this study is suggestive of the overall high rate of change in the genomes of tumors including those of a lower grade. It is hypothesized that some of these altered clones, which manifest as zones of heterogeneity in a solid tumor, may accumulate changes at loci known to influence tumor behavior, and thus clinical outcome.

Brain Neoplasms↗
PubMed2000

Analysis of CAG and CCG repeats in Huntingtin gene among HD patients and normal populations of India.

We have analysed the distribution of CAG and adjacent polymorphic CCG repeats in the Huntingtin gene in 28 clinically diagnosed unrelated Huntington's disease (HD) patients and in normal individuals belonging to different ethnic groups of India. The range of expanded CAG repeats in HD patients varied from 41 to 56 repeats, whereas in normal individuals this number varied between 11 and 31 repeats. We identified six CCG alleles from a total of 380 normal chromosomes that were pooled across different ethnic populations of India. There were two predominant alleles: (CCG)7 (72.6%) and (CCG)10 (20%). We report here for the first time one four-repeat CCG allele which has not been found in any population so far. We found 30 haplotypes (two loci CAG-CCG) for 380 normal chromosomes. In the present study, no statistically significant preponderance of expanded HD alleles was found on either (CCG)7 or (CCG)10 backgrounds. Our studies suggest that the overall prevalence of HD in Indian populations may not be as high as in Western populations. Further studies are necessary to identify the origin of HD mutation in these populations.

Adolescent↗
PubMed2000

Growing skull fracture of ethmoid: a report of two cases.

We describe a rare sequel of ethmoid fracture--a growing skull fracture associated with cerebrospinal fluid rhinorrhoea following trauma sustained in adult life. The natural history of its development, diagnosis, and the results of surgery are discussed. The literature is reviewed with regard to aetiology, incidence, imaging characteristics and management of this rare post-traumatic complication.

Adult↗
PubMed2000

Role of 17p13.3 chromosomal region in determining p53 protein immunopositivity in human astrocytic tumors.

Immunohistochemistry of p53 protein is being increasingly performed as a clinical service as well as in research for prediction of tumor behavior. Although early reports suggested that p53 immunopositivity was associated with p53 gene alterations, recent evidence indicates that this is not always true. Earlier, we had demonstrated the significant association of loss of heterozygosity (LOH) of the chromosomal region 17p13.3 with higher grades of human astrocytic tumors. This was independent of the heterozygosity status of p53. LOH of p53 was taken as an indicator of p53 gene alteration, which was substantiated by sequencing a subset of the tumors. In the present study, we report that p53 immunopositivity in 40 of the same set of tumors (five could not be evaluated because of paucity of tissue) was significantly associated with LOH of 17p13.3 region (Fisher's exact two-tailed, P = 0.012; odds ratio, 12) but not with LOH of p53 (Fisher's exact two-tailed, P = 0.324; odds ratio, 2.24). This indicates that the gene(s) on the 17p13.3 region of the human chromosome may be influencing the p53 immunopositivity status of glial tumors and possibly other tumors in general. This has great implications in interpreting p53 immunohistochemistry results of biopsies of various tumor types as due to p53 mutations alone. The study thus points to a new molecular correlate for p53 immuno-positivity in tumors.

Brain Neoplasms↗
PubMed2000

Hypophyseal tuberculoma: direct radiosurgery is contraindicated for a lesion with a thickened pituitary stalk: case report.

OBJECTIVE AND IMPORTANCE: Hypophyseal tuberculomas are extremely rare lesions. The recognition of hypophyseal tuberculomas in the differential diagnosis of pituitary tumors is important, even with no evidence of systemic tuberculosis. CLINICAL PRESENTATION: A 27-year-old female patient presented with continuous, dull, generalized headaches and amenorrhea, with no history of visual diminution, galactorrhea, or endocrinological abnormalities and no evidence of systemic tuberculosis. The patient exhibited a normal water balance, without polyuria or polydipsia. A gynecological examination, including an endometrial biopsy for amenorrhea, did not reveal any abnormalities. Perimetric and endocrinological examination results were normal. Contrast magnetic resonance imaging revealed a dense enhancing intrasellar mass, with thickening of the pituitary stalk. INTERVENTION: Sublabial rhinoseptal transsphenoidal decompression of the lesion was performed. The histopathological features were consistent with a diagnosis of tuberculoma, and acid-fast bacilli were demonstrated in the surgically removed tissue with Ziehl-Neelsen staining. As soon as the histopathological features were known, the patient underwent a lumbar puncture for cerebrospinal fluid analysis, which indicated normal findings. An intradermal tuberculin test yielded negative results. The patient was treated with medical therapy for 18 months, and complete resolution of the lesion was observed in follow-up examinations. CONCLUSION: Hypophyseal tuberculomas are often mistaken for pituitary adenomas. The finding of a thickened pituitary stalk in contrast magnetic resonance imaging scans may be useful for the differentiation of these lesions from pituitary adenomas. Direct radiosurgery is not an appropriate primary treatment method for pituitary adenomas and is principally restricted to elderly, medically unfit patients with microadenomas and patients with residual or recurrent tumors after microsurgery. It is contraindicated for patients who exhibit a thickened pituitary stalk in contrast magnetic resonance imaging scans.

Adult↗
PubMed2000

Defining the regulatory factors required for epidermal gene expression.

Keratins K5 and K14 are the hallmarks of mitotically active keratinocytes of stratified epithelia. They are transcribed at a high level and in a tissue-specific manner, enabling us to use the K14 gene to elucidate the regulatory mechanism underlying epidermis-specific transcription. We have identified four DNase I-hypersensitive sites (HSs) present in the 5' regulatory sequences of the K14 gene under specific conditions where the gene is actively expressed. Two of these sites (HSsII and -III) are conserved in position and sequence within the human and mouse K14 genes. Using an in vivo transgenic approach and an in vitro keratinocyte culture approach, we have discovered that most of K14's transcriptional activity is restricted to a novel 700-bp regulatory domain encompassing these HSs. This enhancer is sufficient to confer epidermis-specific activity to a heterologous promoter in transfection assays in culture and in transgenic mice in vivo. A 125-bp DNA fragment encompassing HSsII harbors the majority of the transactivation activity in vitro, and electrophoretic mobility shift and mutational assays reveal a role for AP-1, ets, and AP-2 family members in orchestrating the keratinocyte-preferred expression of HSsII. The HSsII element also confers epidermal expressivity to a heterologous promoter in transgenic mice, although it is not sufficient on its own to fully restrict activity to keratinocytes. Within the HSsII element, the ets and AP-2 sites appear to be most critical in collaborating to regulate epidermal specificity in vivo.

Amino Acid Sequence↗
PubMed2000

Expression profile and chromosomal location of cDNA clones, identified from an enriched adult retina library.

PURPOSE: To delineate the profile of genes expressed in the adult human retina and assign chromosomal location of cDNA clones. METHODS: The end-sequence of random clones from an enriched human retinal cDNA library was analyzed by NCBI database search. Expression profile was established by northern blot analysis, database search, or both. Selected cDNA clones were localized to human chromosomes by somatic cell hybrid analysis, in situ hybridization to metaphase chromosomes, or both. Chromosomal location was also obtained by searching the databases. RESULT: One hundred and thirty-seven clones were isolated from the subtracted retinal library. Fifty-one clones were identical with 35 known human genes in GenBank, and 24 clones corresponded to 23 uncharacterized human expressed sequenced tags (ESTs), novel genes, or both. The remaining 59 clones were not pursued further because they contained bacterial sequences or repetitive elements. Several clones indicated a restricted pattern of expression with high levels of transcripts in the retina. Chromosomal location of novel retinal ESTs is also reported. CONCLUSIONS: This study provides a profile of genes expressed in the adult human retina. One round of subtraction eliminated most constitutively expressed genes and permitted partial normalization of the retinal library. Twenty-three novel genes were identified. The combined information obtained from expression analysis and chromosomal localization of retinal cDNAs should be valuable in identifying candidate genes for diseases involving retinal dysfunction.

Blotting, Northern↗