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Biomedical subjects

S Rao

Publications and source records attributed to S Rao.

At least 217 records · Page 12Linked to original sources

Surgical treatment of refractory epilepsy associated with space occupying lesions. Experience and review.

Surgery for space occupying lesions of the brain associated with intractable epilepsy represents a special problem because relief of the epilepsy in as much an operative goal as excision of the space occupying lesion itself. This study concerns 32 patients with space occupying lesions and intractable epilepsy who underwent excision of the lesion with acute intraoperative electrocorticography guided resection of the epileptogenic focus. Of the 32 patients, 16 formed a subgroup of gangliogliomas alone. The remaining were mixed lesions, predominantly benign. The duration of seizures in these patients ranged from 2 to 30 years, and the seizure frequency varied from 1 to 300 convulsions per month. The operative procedures included temporal corticectomy, amygdalo-hippocampectomy, and extratemporal corticectomies. Twenty nine patients were in Engel class I postoperatively, and three patients were in Engel class II. The findings with gangliogliomas were also considered in a separate group. This study strongly suggests that the operative procedure under electrocorticography guidance improves seizure outcome in space occupying lesions related intractable epilepsy.

Adolescent↗

Alleviation of the temperature-sensitive paralytic phenotype of shibire(ts) mutants in Drosophila by sub-anesthetic concentrations of carbon dioxide.

Cellular mechanisms involved in general anesthesia are unknown. We report here that sub-anesthetic concentrations of carbon dioxide specifically suppress the temperature-sensitive paralytic phenotype of Drosophila shibire(ts) mutants that have a conditional block in synaptic vesicle recycling. Carbon dioxide not only suppresses the onset of temperature-sensitive paralysis, but also rapidly reverses paralysis induced at the restrictive temperature. This effect of CO2 is most pronounced at about 35% in air, and depends on the absolute concentration of available carbon dioxide rather than on the ratio of oxygen to CO2. Other general anesthetics, halothane, N2 or argon do not suppress the paralytic phenotype of shibire significantly at concentrations we tested. Paralysis of the other temperature sensitive paralytic mutants in our collection is not suppressed by carbon dioxide. These behavioral observations are discussed in the light of possible mechanisms underlying paralysis of shi(ts) flies. We suggest that spontaneous seizures induced in shi(ts) flies held at their restrictive temperatures cause vesicle depletion at critical synapses and consequent behavioral paralysis. The effect of subanesthetic concentrations of CO2 may be to depress spontaneous CNS activity, thus raising the threshold temperature at which synaptic vesicle depletion occurs. In support of this model, we show that the threshold temperature for paralysis is reduced in shi(ts) flies when CNS activity is increased by pharmacological or genetic manipulations, and that subanesthetic concentrations of CO2 aggravate, rather than alleviate, the t.s. paralytic phenotype of hypoactive parats flies defective in axonal voltage-gated sodium channels.

Alleles↗

Gender differentials in the social impact of leprosy.

Prevalence rates of leprosy have reduced considerably in many states where multidrug therapy is in operation. However, reduction in prevalence alone is not sufficient as the social consequences of the diseases on the life of the patient are often severe and persist even after its cure. The present paper, therefore, investigates social impact with special reference to gender differentials. Data obtained from structured questionnaires (n = 606) is analysed for this purpose. It was observed that the initial delay in identifying the skin changes as the symptoms of the disease were higher for females (29 months) than males (24 months). Even after identifying the symptoms, women were observed to depend exclusively on nonmedical treatment for a longer period (10 months) than males (6 months). Upon starting the medical treatment females were observed to be more compliant than males, but the benefits of regularity appeared to be outweighed by the initial delay in starting medical treatment. The social impact on daily life was more severe for females than males as revealed by the isolation from daily activities, such as, restrictions on participation in familial functions, restrictions on touching children. The paper highlights implications of gender bias on detection and treatment, and suggests modifications for control programmes.

Adolescent↗

Effect of Ti, Al, and V ions on the relative growth rate of fibroblasts (L929) and osteoblasts (MC3T3-E1) cells.

The effect of Ti, V and Al ions on the relative growth rate of L929 cells and MC3T3-E1 cells was investigated by a cell culture method with metallic powders. These powders were sterilized under a U.V. lamp for 6 h, suspended in the medium and extracted for 48 h, 72 h and 96 h in the incubator. After filtering with a 0.2 microns filter, 3.0 x 10(4) L929 cells and 5 x 10(4) MC3T3-E1 cells were seeded in these filtrates of the medium with and without (control) the presence of the metallic powder. The number of cells was counted using a coulter counter from 1 to 7 days. The number of L929 cells after 4 days of incubation was almost similar for Ti and the control, whereas in the case of A1 and V extraction the number of cells was too low as compared to that of the control. The relative growth rate of L929 cells for Ti, A1 and V after 4 days of incubation was about 1, 0.2 and 0.02, respectively. A similar trend was also observed for MC3T3-E1 cells. The effect of the relative growth rate of L929 cells at different extraction times of 48 h, 72 h and 96 h was examined. It was found that the relative growth rate of L929 cells for Ti, A1 and V extraction was almost the same at all three extraction times. A number of 2.0-5.0 x 10(4) cells was seeded in the medium of A1 extraction. The effect of this initial number of cells on the relative growth rate of L929 cells was investigated. The relative growth rate of L929 cells decreased as the initial number of L929 cells increased. Moreover, dilutions from 1 to 10 times in the case of A1 and from 1 to 4000 times in the case of V were made. The relative growth rate became equal to 1 at 5 times dilution for A1 and at 4000 times dilution for V, for both L929 and MC3T3-E1 cells. From the measures of the concentration of the released A1 and V ions on the relative growth rate of L929 cells, it could be seen that there was a marked decrease in the concentrations of A1 and V ions from 0.3 ppm to 0.1 ppm.

Aluminum↗

Double jeopardy: women and leprosy in India.

This article presents evidence from two states of India, Bihar and Maharashtra, on the process of "dehabilitation" among male and female leprosy patients, and suggests gender-sensitive interventions to address existing problems in leprosy control. While the study investigated a wide range of gender differences in the impact of leprosy, this article focuses on only two-marriage and family reactions. Important gender differences were apparent in the impact of the disease. While both men and women were negatively affected in terms of their family and marital lives, women suffered more isolation and rejection. Psychologically, women appeared more vulnerable because they were deprived of personal contact with others in the domestic environment where they were accustomed to receiving their greatest emotional rewards. Women reported that indifference to them by other family members, or seeming negation of their presence, caused them the greatest suffering. This underscores the importance of providing information to both leprosy patients and their families about the disease and its treatment, including the possibility of cure with MDT (multi-drug therapy) and of counselling family members about their crucial role in helping patients cope and recover. This support is even more critical for women, who often lack access to the variety of outside advice and assistance available to men. The evidence presented in the article demonstrates the importance of analysing leprosy from a gender perspective, not only because this approach helps to inform our understanding of the determinants and consequences of the disease, but also because it provides new insights for improved disease control.

Adolescent↗

Pilot study on plasma fatty acids in poorly controlled non insulin dependent diabetic Melanesians.

Different data have been reported with respect to the distribution of plasma and tissue fatty acids in patients with diabetes mellitus and some studies have suggested that severe diabetes is required to produce the fatty acid abnormalities observed in the diabetic rat. We studied the plasma fatty acid profile with particular attention to the omega 3 and 6 fatty acids in 14 non insulin dependent (NIDDM) diabetic Melanesians, majority of whom were poorly controlled (mean glycosylated haemoglobin levels of 12.8%), their mean age was 43.0 +/- 6.3 with disease duration of 5.2 +/- 4.8 years. Plasma fatty acids were estimated by gas chromatography (GC) using a flame ionisation detector (FID). Each diabetic was age and sex matched with a non diabetic, healthy control. Though the plasma concentrations of arachidonic (20:4, omega-6), eicosapentanoic (20:5 omega-3) and docosahaxaenoic (22:6 omega-3) acids were lower than in control subjects, these values were of no significant difference. Similarly, no significant differences were observed between the total plasma saturated fatty acids (palmitic and stearic acids) of diabetic and control subjects. The results of this pilot study suggest that poor metabolic control may not be associated with plasma fatty acid abnormalities in NIDDM patients.

Adult↗

A pilot study on plasma fatty acids in poorly controlled non insulin dependent (type 2) Melanesian diabetics.

Different data have been reported with respect to the distribution of plasma and tissue fatty acids in patients with Diabetes mellitus and some studies have suggested that severe diabetes is required to produce the fatty acid abnormalities observed in the diabetic rat. We studied the plasma fatty acid profile with particular attention to the omega three and six fatty acids in 14 non insulin dependent (NIDDM) Melanesian diabetics the majority of whom were poorly controlled (mean glycosylated haemoglobin levels of 12.89pc), their mean ages were 43.0 + 6.3 with a duration of 5.2 + 4.8 years. Plasma fatty acids were estimated by gas chromatography (GC) using a flame ionization detector (FID). Each diabetic was age and sex matched with a non diabetic healthy control. Through the plasma concentrations of arachidonic (20:4, w-6), eicosapentanoic (20:5, w-3) and docosahaxaenoic (22:6, w-3) acids were lower than in control subjects, these values were of no significant difference. Similarly, no significant differences were observed between the total plasma saturated fatty acids (palmitic and stearic acids) of diabetic and control subjects. The results of this pilot study suggest that poor metabolic control may not be associated with plasma fatty acids abnormalities in NIDDM patients.

Adult↗

Characterization of the taxol binding site on the microtubule. 2-(m-Azidobenzoyl)taxol photolabels a peptide (amino acids 217-231) of beta-tubulin.

Photoaffinity labeling methods are being used to define the molecular contacts between taxol and its target protein, tubulin. Our laboratory has demonstrated previously that [3H]3'-(p-azidobenzamido)taxol photolabels the N-terminal 31 amino acids of beta-tubulin (Rao, S., Krauss, N.E., Heerding, J.M., Swindell, C.S., Ringel, I., Orr, G.A., and Horwitz, S.B. (1994) J. Biol. Chem. 269, 3132-3134). The interaction of a second photoaffinity analogue of taxol, [3H]2-(m-azidobenzoyl)taxol, with tubulin has been investigated. This analogue specifically photolabels beta-tubulin and the photolabeling is completed by both taxol and unlabeled 2-(m-azidobenzoyl)-taxol indicating a common binding domain. To identify the site(s) of photoincorporation, [3H]2-(m-azidobenzoyl)taxol-photolabeled beta-tubulin was subjected to sequential cyanogen bromide and tryptic digestions. Radiolabeled peptides were purified by reverse phase high performance liquid chromatography, and amino acid sequencing studies identified a peptide containing amino acid residues 217-231 of beta-tubulin as the major photolabeled domain.

Affinity Labels↗

Characterization of acute promyelocytic leukemia cases with PML-RAR alpha break/fusion sites in PML exon 6: identification of a subgroup with decreased in vitro responsiveness to all-trans retinoic acid.

Of 113 acute promyelocytic leukemia cases documented to have diagnostic PML-RAR alpha hybrid mRNA, 10 cases (8.8%) had fusion sites in PML gene exon 6 (V-forms) rather than in the two common hybrid mRNA configurations resulting from breaksites in either PML gene intron 6 (L-forms) or intron 3 (S-forms). In 4 V-form cases, a common break/fusion site was discovered at PML gene nucleotide (nt) 1685, abutting a 3' cryptic splice donor sequence. The fusion site was proximal to the common site in 1 case and more distal in 5 cases. The open reading frame encoding a PML-RAR alpha gene was consistently preserved, either by an in-frame fusion site or by the insertion of 3 to 127 unidentified nts. In 2 V-form cases, hybridization analysis of the reverse transcriptase-polymerase chain reaction products with a PML-RAR alpha juction probe was required for discrimination from L-form cases. Two V-form subgroups were defined by in vitro sensitivity to all-trans retinoic acid (tRA)-induced differentiation: 4 of 4 cases tested with fusion sites at or 5' to nt 1685 (subgroup E6S) had reduced sensitivity (EC50 > or = 10(-7) mol/L), whereas 4 of 4 cases with fusion sites at or 3' to nt 1709 (subgroup E6L) had high sensitivity (EC50 < 10(-8) mol/L) indistinguishable from that of L-form and S-form cases. These results provide the first link between PML-RAR alpha configuration and tRA sensitivity in vitro and support the importance of subclassifying APL cases according to PML-RAR alpha transcript type.

Adult↗

Overexpression of the T-cell receptor beta-chain variable region TCRBV14 in HLA-A2-matched primary human melanomas.

We have shown previously that peripheral blood lymphocytes (PBL) of patients with metastatic melanoma include cytotoxic T-cell clones that recognize Melan-A/MART-1 in a HLA-A2-restricted fashion. Such clones preferentially use the variable (V) regions TCRBV14 or TCRBV7 in the beta-chain of their T-cell receptor (TCRB). It was not known, however, whether this finding is associated with the presence of the HLA-A2 allele in tumor tissue and whether evidence of the predominance of these TCRBV families can also be observed in primary tumor tissue. To address these issues, we have used a semiquantitative PCR to examine the TCRBV repertoire in six HLA-A2-matched primary melanomas in comparison with their autologous PBL. Although each patient had his or her own pattern of skewed TCRBV utilization, in all patients, T-cells that used TCRBV14 were significantly overrepresented in the neoplastic site compared with PBL. All of the primary tumors studied had detectable expression of Melan-A/MART-1 and gp100, and immunohistochemical analysis confirmed the presence of the HLA-A2 allele. Additional samples of Melan-A/MART-1-positive, gp100-positive primary melanomas from six non-HLA-A2 patients and four autologous normal skin controls failed to reveal a TCRBV14 predominance in such tissues. These results point to a role of TCRBV14 T lymphocytes in the HLA-A2-restricted immune recognition of primary melanomas.

Base Sequence↗

Evaluation of the effectiveness of the Minerva cervicothoracic orthosis.

STUDY DESIGN: This study evaluated a lightweight Minerva cervicothoracic orthosis with an occipital flare and forehead strap. OBJECTIVE: The orthosis was evaluated for its ability to immobilize the cervical spine in normal healthy volunteers. SUMMARY OF BACKGROUND DATA: Previous studies have been performed to evaluate cervical orthoses. Exception for the halo brace, none have controlled the upper cervical spine very well. The brace tested in the present report incorporates an occipital flare and forehead strap to better control the upper cervical spine. METHODS: Sixteen healthy male volunteers were evaluated in and out of the orthosis in three planes of motion. Maximal active cervical flexion, extension, and lateral bending were recorded and measured radiographically. Rotation was measured from overhead photographs. RESULTS: In a comparison of the present results with those of similar previous studies, improvement in control of flexion/extension of the upper cervical spine and in control of rotation was found. The occiput to C1 level, however, remained poorly controlled. CONCLUSION: This orthosis provides good control of the cervical spine below C1.

Braces↗

A technique for porcine hepatocyte harvest and description of differentiated metabolic functions in static culture.

Current bioartificial liver devices are based on the use of a large mass of hepatocytes exhibiting differentiated metabolic function. The pig has become a source of interest for the acquisition of such cells-however, harvesting a large mass of highly viable cells has met with difficulty. This study describes a technique for harvesting large quantities of hepatocytes at viabilities greater than 90% and also describes several features documenting differentiated function. Pigs, 6 to 10 kg body weight, underwent in situ two-step whole liver perfusion (ethylene glycol tetraacetic acid and collagenase) and ex vivo cell harvest. Harvests yielded an average of 19.5 billion cells with an average viability of 94.6%. Hepatocytes were then entrapped in type I collagen (3 x 10(5) cells/well) and cultured in serum-free media for 5 days. Pig hepatocytes produced stable amounts of albumin and maintained cytochrome P-450 and glucuronidation activity over 5 days, as shown by the metabolism of lidocaine and 4-methylumbelliferone. These data indicate that pig hepatocytes can be harvested with high yields and can retain viability and differentiated function over at least 5 days of culture, and therefore should prove to be an excellent source of hepatocytes for bioartificial liver devices.

Animals↗

Gel-entrapment bioartificial liver therapy in galactosamine hepatitis.

A need exists for an effective, safe bioartificial liver to support patients in fulminant hepatic failure (FHF). The purpose of this study was to determine the treatment efficacy of the novel gel-entrapment porcine hepatocyte bioartificial liver (BAL) in a fatal model of canine hepatic failure. FHF was produced in 27- to 30-kg halothane-anesthetized dogs by bolus infusion of the hepatotoxin D-galactosamine (D-Gal). Three groups were studied during the 48-hr experiment: Group D-Gal (n = 5) received galactosamine, 1.0 g/kg, iv at Time O, Group HepBAL (n = 5) received D-Gal followed by continuous hemoperfusion with the BAL device loaded with approximately 6 billion viable pig hepatocytes starting at Time 24 hr, and three dogs served as healthy controls (Group Control) and received no galactosamine. The primary endpoints were survival and coma development. Group D-Gal demonstrated 100% mortality from liver failure by 42 hr, characterized by a progressive rise in liver enzymes, total bilirubin, ammonia, and lactate and associated with coagulopathy, hypoglycemia, coma, and brain death. BAL therapy significantly delayed the onset of coma and improved survival (median 47 hr vs D-Gal median 36 hr). A significant delay in the rise of lactate and ammonia was also noted. BAL therapy prolonged survival and improved both laboratory and clinical markers of fatal liver failure. These data indicate that this BAL may have clinical utility in supporting human liver failure.

Animals↗

Sympathetic skin response in Guillain-Barré syndrome.

Dysautonomia is a common feature of Guillain-Barré (GB) syndrome and is sometimes the cause of significant morbidity and death. Changes in sympathetic skin response (SSR) may be one of the accompaniments of dysautonomia. An attempt was made to correlate SSR changes with clinical and electrophysiologic features in a group of 24 patients with GB syndrome fulfilling NINDS (National Institute of Neurological Disorders and Stroke) criteria. A total of nine patients had absent SSR. Thirteen patients had clinical dysautonomia, of whom five had absent SSR. Five patients had features of predominant axonal damage and preserved SSR. A trend towards correlation of SSR abnormalities with common peroneal nerve conduction parameters (velocity and compound muscle action potential amplitude) was noted. We conclude that SSR abnormalities are common in GB syndrome and may be complementary to bed-side tests for autonomic dysfunction.

Action Potentials↗

Laser Doppler velocimetry and platelet-derived growth factor as prognostic indicators for the healing of ulcers and ischaemic lesions of the lower limb.

The prognostic potential of skin blood flow measured by laser Doppler and serum platelet-derived growth factor (PDGF) levels was evaluated in patients with ischaemic lesions or ulceration of the lower limb. The laser Doppler-derived skin blood flow and perfusion pressure were measured in 93 patients with ischaemic lesions or ulceration in 98 lower limbs. Of these lesions, 61% healed spontaneously or with conservative local therapy, while 39% required major surgery. The likelihood for healing was reduced by older age. Comparison of receiver operating curves demonstrated that the optimal sensitivity and specificity were obtained for a combination of skin blood flow and perfusion pressure measured at 44 degrees C rather than at room temperature. If the skin perfusion pressure and blood flow were greater than 15 mmHg and 100 U respectively at 44 degrees C, 91% lesions healed, while if they were less than these values none healed. This provided a sensitivity and specificity of 100% and 83% respectively. The serum PDGF concentration was measured by radioimmunoassay in 48 patients with ischaemic lesions or ulceration of the lower limb, and compared with that in 34 healthy controls and 15 patients who had undergone abdominal surgery 3-5 days previously. The median PDGF level in the control group (83 pmol/l) was significantly less than that in the post-laparotomy group (217 pmol/l). The median PDGF level in the 31 patients whose ulcers healed with conservative therapy (210 pmol/l) was significantly higher compared with that in the 17 patients with unhealed ulcers (70 pmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗