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Biomedical subjects

R Raghavan

Publications and source records attributed to R Raghavan.

At least 55 records · Page 3Linked to original sources
PubMed1995

In vivo and in vitro studies on the neurotoxic potential of 6-hydroxydopamine analogs.

In an attempt to determine which physical and biological properties could best be correlated with neurotoxic potential, seven analogs of 1-(2,4,5-trihydroxyphenyl)-2-aminoethane (1), better known as 6-hydroxydopamine, were synthesized and compared to 1 in a variety of ways both in vivo and in vitro. The analogs, in combination with the standard 1, include all eight of the 2,4,5-trisubstituted-phenyl derivatives of phenethylamine and alpha-methylphenethylamine in which the substitution is of the trihydroxy or aminodihydroxy form. Low (60 nmol) and high (300 nmol) intracerebroventricular doses of all analogs produced long-term (7 day) reduction of mouse whole brain norepinephrine (NE) and lesser depletions of dopamine (DA), and effects on serotonin were varied. The analog 1-(5-amino-2,4-dihydroxyphenyl)-2-aminopropane (8) was both more complete and more selective than the standard 1 in depleting NE. Using a histofluorometric glyoxylic acid method and Fink-Heimer silver degeneration stain, it was determined that overt neural degeneration was produced by 8. In vitro, the ease of oxidation of the eight analogs was found to be represented by a formal potential range of -130 to -212 mV vs SCE. However, there was no obvious relationship between ease of oxidation and the extent of monoamine depletion from mouse brain. Using kinetic analysis of synaptosomal accumulation of [3H]NE and [3H]DA, it was found that the standard 1 is more potent in its interaction with the DA uptake site (Ki = 12 +/- 0 microM) than the NE uptake site (Ki = 51 +/- 1 microM). A correlation analysis was used to determine that differences in NE and DA depletion by each analog could not be explained by differences in potency for in vitro uptake blockade. However, there was a correlation between the Ki for [3H]NE uptake blockade and the EC50 for synaptosomal release of preloaded [3H]NE for the eight analogs (R2 = 0.96; for log:log plot, R2 = 0.54), indicating that the results for these two in vitro tests both reflect interaction with the same NE neuronal membrane transport site. A similar correlation between Ki and EC50 was shown for all eight analogs using [3H]DA (R2 = 0.92; for log:log plot, R2 = 0.52), indicating interaction with the same DA neuronal membrane transport site. These findings demonstrate that there is no single property that can account for selectivity of action and/or potency of catecholamine neurotoxins related to 6-hydroxydopamine.

Animals↗
PubMed1995

Rapid cycling bipolar affective disorder and familial learning disability associated with temporal lobe (occipitotemporal gyrus) cortical dysplasia.

This case report describes a hitherto unreported association between temporal cortical dysplasia and rapid cycling bipolar affective disorder in a learning disabled young man with a family history of rapid cycling bipolar affective disorder in two dysmorphic and learning disabled maternal uncles, and probably learning disability in the mother and grandmother. An identical family with similar findings could not be located in the English literature.

Adult↗
PubMed1994

Apolipoprotein E epsilon 2 allele promotes longevity and protects patients with Down's syndrome from dementia.

Although individuals with Down's syndrome nearly always develop the clinical and pathological features of Alzheimer's disease, some clearly do not become demented despite living into their sixth and seventh decades. Genetic variation at the apolipoprotein E locus has recently been shown to be an important determinant of Alzheimer's disease, with the epsilon 4 allele having been shown to be associated with the disease and, at least in some cases, the epsilon 2 allele being negatively associated with the disease. Here we show, in a series of clinically assessed individuals with Down's syndrome, that the epsilon 2 allele of ApoE is associated with both longevity and the absence of clinical evidence of dementia. These data show that the clinical phenotype of Down's syndrome can be modulated by genes on chromosomes other than chromosome 21. The importance of this observation to the pathogenesis of Alzheimer's disease, both in Down's syndrome and in general, is discussed.

Age of Onset↗
PubMed1994

Senile dementia of the Lewy body type has an apolipoprotein E epsilon 4 allele frequency intermediate between controls and Alzheimer's disease.

We have examined the apolipoprotein E (ApoE) allele distributions in Alzheimer's disease, Parkinson's disease, senile dementia of the Lewy body type and neurologically normal controls. We have confirmed the strong genetic association between the epsilon 4 allele and Alzheimer's disease, shown that there is no association between the epsilon 4 allele and Parkinson's disease and shown that senile dementia of the Lewy body type has an epsilon 4 allele distribution intermediate between Alzheimer's disease and Parkinson's disease. On this basis, we suggest that senile dementia of the Lewy body type represents the co-occurrence of two syndromes.

Aged↗
PubMed1994

Gender differences in the phenotypic expression of Alzheimer's disease in Down's syndrome (trisomy 21).

Twenty-eight individuals with typical Down's syndrome (DS) phenotype (17 males and 11 females; age range: 10-74 years) were investigated for gender differences in the phenotypic expression of Alzheimer-type pathology (ATP). Quantitative neuropathology was performed in the 4 neocortical lobes of the right hemisphere, by counting senile plaques (SP), and neurofibrillary tangles (NFT). ATP was present in 25 middle-aged (> 40 years) individuals (16 males and 9 females). Females had significantly higher (p = 0.03) mean neocortical NFT densities (36.6 per mm2; s.e.m. +/- 6.6) than males (17.9 per mm2; s.e.m. +/- 4.7). None of the females had NFT densities below 10 per mm2, compared with 6 males in whom NFT were either absent or seen in very low densities (< 4 per mm2). Assessment of SP densities in the same cortical regions showed non-significant differences in females (42.4 per mm2; s.e.m. +/- 5.1) compared with males (33.6 per mm2; s.e.m. +/- 2.1). There was clinical evidence of dementia in all the female (8/8) individuals who were prospectively assessed, compared with only 54% (7/13) of males. The male individuals without clinical dementia had absent or low neocortical NFT densities regardless of high SP densities. Female DS cases (mean age: 48.8 years; s.e.m. +/- 1.9) had an earlier onset of dementia than males (mean age: 53.6 years; s.e.m. +/- 1.3; p = 0.05). Female middle-aged DS individuals have an earlier onset, and a more severe form of AD which correlates with higher neocortical NFT rather than SP density.

Adenosine Triphosphate↗
PubMed1994

Craniofacial pattern of parents of children having cleft lip and/or cleft palate anomaly.

The craniofacial patterns of 38 sets of parents who had children with cleft lip and/or cleft palate anomalies (experimental group) were compared with the 24 sets of parents of healthy (noncleft) children (control group). Using a computerized program, 248 cephalograms (124 lateral and 124 frontal) were digitized and analyzed. The parents in the experimental group exhibited a distinct craniofacial morphology, including a significant decrease in upper anterior facial height (N-Ans) and total anterior face height (V-Gn). Anterior nasal spine (Ans) and maxillary alveolar process (A) were positioned more anteriorly and superiorly in the experimental group, which contributed to a significant increase in the length of the palate (Ans-Pns) and an anterosuperior rotation of the palatal plane. The cranial base angle in the experimental group was significantly obtuse and the articular angle was smaller than that of the controls. The counterclockwise rotation of the mandible was mitigated by a significant increase in the gonial angle. Parents in the experimental group also tended to have faces which were smaller in both transverse and vertical dimensions.

Adult↗
PubMed1994

Oncoprotein immunoreactivity in human pituitary tumours.

OBJECTIVE AND DESIGN: The immediate early gene locus AP-1, incorporating the cellular oncogenes c-fos and c-jun (and their oncoprotein products Fos and Jun respectively) play a key role in regulating cell growth and differentiation. The myc-gene is also known to promote cell growth. In order to investigate the possible role of these oncogenes in human pituitary adenomas, Fos, Jun and Myc oncoprotein immunoreactivities were assessed in surgically resected pituitary adenomas in relation to in-vivo characteristics (hormone secretion, size and invasiveness) and an in-vitro index of cell proliferation (Ki-67 immunoreactivity). Thirty-three human pituitary adenomas and 16 normal pituitary glands were examined. MEASUREMENTS: Oncoprotein immunoreactivity was recorded as present (+) or absent (-), and Ki-67 labelling indices were scored quantitatively. Tumour size was scored from CT scan appearances and radiographic evidence of bone erosion was noted. RESULTS: Oncoprotein immunoreactivity was present in a total of 32/33 cases. Myc immunoreactivity was restricted to the only ACTH-secreting tumour in the series (1/33). Ki-67 immunoreactivity was present in 24/32 cases and labelling indices varied from 0.1 to 3.2%. CONCLUSIONS: Oncoprotein immunoreactivity did not correlate with hormonal profile, bone erosion or the size of the proliferating compartment estimated by Ki-67 labelling indices. Although oncoprotein expression is common in human pituitary adenomas, its significance remains to be elucidated.

Adenoma↗
PubMed1993

Detection of Lewy bodies in Trisomy 21 (Down's syndrome).

The presence of cortical senile plaques and neurofibrillary tangles sufficient to warrant a neuropathological diagnosis of Alzheimer's disease is well established in middle-aged individuals with Trisomy 21 (Down's syndrome). In contrast a relationship between Down's syndrome and Lewy bodies, one of the major neuropathological features of Parkinson's disease, has not been previously reported. In a clinico-neuropathological survey of 23 cases of Down's Syndrome, two patients, aged 50 and 56 years respectively, were found to have Lewy body formation in the substantia nigra in addition to cortical Alzheimer-type pathology. Neither case showed significant substantia nigra neuron loss although locus coeruleus loss was present in both. Since substantia nigra Lewy bodies are a characteristic neurohistological feature of idiopathic Parkinson's disease, their occurrence in cases of Down's syndrome with evidence of Alzheimer-type pathology supports an aetiopathological connection between Parkinson's disease, Alzheimer's disease, and Down's syndrome; and suggests that common pathogenic mechanisms may underlie aspects of neuronal degeneration in these three disorders, some of which may relate to aberrant chromosome 21 expression.

Adult↗
PubMed1991

Multi-phasic Questionnaire profile of alcoholics and related factors.

Thirty alcoholics treated as inpatients were administered the Multi-phasic Questionnaire (MPQ), a short version of MMPI, to study their personality pattern. Results showed highest loading on depression (85%) and lowest on anxiety (3%). A significant correlation was found between scales of psychopathic deviance and hysteria. Age of problem drinking under 35 years and poor PQ level were found to be associated with depression and psychopathic deviance. Clinical diagnosis was corroborated by the findings of the MPQ. The findings of the present study may be utilised to screen adolescents from alcoholic families for preventive measures.

Adult↗
PubMed1990

Hutchinson-Gilford progeria: familial occurrence.

We report on 2 brothers with Hutchinson-Gilford progeria. These patients have 2 unusual findings, i.e., marked resorption of the mandible along with loss of teeth in the elder sib and prolonged survival. Both sibs are still alive and active at the age of 32 and 24 years.

Abnormalities, Multiple↗
PubMed1990

Cell proliferation patterns in the diagnosis of astrocytomas, anaplastic astrocytomas and glioblastoma multiforme: a Ki-67 study.

Although astrocytomas, anaplastic astrocytomas and glioblastoma multiforme differ in their clinical courses, histological distinction between these three tumours and between astrocytomas and anaplastic astrocytomas in particular may be unclear on histology alone especially in small biopsies. In the present study, a more objective way of distinguishing between the three types of tumour is sought. Frozen sections from 26 astrocytomas, 26 anaplastic astrocytomas and 38 glioblastomas were stained by an indirect immunoperoxidase technique using the monoclonal antibody Ki-67 which binds to nuclear proteins in the G1, S, G2 and M phases of the cell cycle. The Ki-67 staining was assessed quantitatively through direct observation of the stained sections by the use of a drawing tube attached to a microscope. A minimum of 1000 cells was counted in each case and labelled cells were expressed as a percentage of the total number of cells. These results, when correlated in each case with the histology of the tumour in paraffin sections, showed Ki-67 labelling indices ranging from 0 to 1.9% (mean 0.5% SD +/- 0.54) in astrocytomas, 0.6 to 10.9% (mean 4.1% SD +/- 2.8) in anaplastic astrocytomas and 0.9 to 16.2% (mean 6.4% SD +/- 3.34) in glioblastoma multiforme. The differences in the three types of tumour were statistically significant. The results suggest that Ki-67 staining is a useful addition to the panel of techniques for distinguishing between astrocytomas, anaplastic astrocytomas and glioblastoma multiforme.

Antibodies, Monoclonal↗
PubMed1989

Cognitive functioning of alcoholics and its relationship with prognosis.

In a preliminary study a group of 30 alcoholics were subjected to psychological tests to explore the influence of regular alcohol intake on their cognitive functioning and its relationship with prognosis. The functions chosen were, arousal and maintenance of attention, verbal intelligence and performance intelligence. Tests used were the Binet Kamat test of intelligence and Bhatia short scale. Level of education was positively correlated with attention-span and verbal intelligence, but not with performance intelligence. The inter-test discrepancy alone on the performance intelligence test could be assessed for evaluation of cognitive impairment. Poor P.Q. scorers sought medical consultation before their mid thirties and had earlier onset of alcoholism. Elder addicts (above 35 years) showed more abstraction deficiency. The higher the P.Q. the higher was its' positive correlation with adjustment to work, but not to family.

Adult↗