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Biomedical subjects

V Balasubramanian

Publications and source records attributed to V Balasubramanian.

At least 19 recordsLinked to original sources

Virulence of Mycobacterium tuberculosis for guinea pigs: a quantitative modification of the assay developed by Mitchison.

One of the more accepted methods of assay of virulence of tubercle bacilli is one developed by Mitchison in which guinea pigs were infected by the intramuscular route with 1.0 mg of tubercle bacilli freshly harvested from Lowenstein Jensen medium and in which virulence was based on a subjective score of the extent of gross disease in the animal 6 weeks after infection. Due to the practical difficulties involved in such an assay when routinely performed, the following modifications were made: frozen stocks of the culture were prepared prior to the date of infection, the inoculum was quantitated by means of colony forming units, and virulence was based on the number of tubercle bacilli recovered from the spleen of infected animals 6 weeks after infection. A significant correlation was obtained between the findings from the Mitchison assay of virulence and the modification. The latter assay is recommended for its quantitative and objective features.

Animals

Development and characterization of a whole-cell radioligand binding assay for [125I]gp120 of HIV-1.

The binding of HIV-1 envelope glycoprotein, gp120, to the CD4 receptor is an important step in productive infection. The development of agents which interrupt this binding phenomenon should be of therapeutic interest. The present study characterizes a whole cell gp120/CD4 radioligand binding assay (radioligand binding assay) modified for use in a high volume screening format. Modifications include the use of human CD4 receptor stably expressed in a Chinese hamster ovary cell line and the gentle fixation (paraformaldehyde) of the CD4 receptor just prior to assay. Binding of [125I]gp120 to fixed CD4 was of high affinity (KD = 6 nM), saturable, reversible, and specific. The kinetics of binding were identical to those of viable (non-fixed) CD4 receptor. [125I]gp120 binding was inhibited by unlabeled recombinant gp120, soluble CD4, and the anti-CD4 monoclonals OKT4A and LEU3A. A number of compounds reported to inhibit gp120 binding and/or gp120 induced syncytium formation were also active in this assay. This modified radioligand binding assay was developed to initiate a rational and extensive screening program to assist in the identification of potential chemotherapeutic agents based on their ability to inhibit gp120 binding to host cells.

Animals

Growth characteristics of recent sputum isolates of Mycobacterium tuberculosis in guinea pigs infected by the respiratory route.

The consideration of virulence must distinguish between infectivity and the ability to cause progressive disease once the infection is established. Several investigators have reported the presence of naturally occurring isolates which differ in virulence for guinea pigs. Isolates from south India which differed with respect to gross disease and number of bacilli recovered from spleen after an intramuscular infection also differed in their efficiencies to initiate an infection, once inhaled and retained. Also, this difference was correlated with differences in the rate of multiplication at the site of implantation and rate of multiplication at sites of hematogenous seeding, as well as the extent of hematogenous seeding. The number of metastatic foci was identified as a quantitative measure of hematogenous seeding, which was not confounded by the rate of multiplication of bacilli. Even allowing for the fourfold-reduced efficiency of low-virulence tubercle bacilli to produce a lesion, this measure clearly revealed a significantly reduced ability of the low-virulence tubercle bacilli to disseminate via the bloodstream.

Aerosols

A guinea pig model of experimental airborne tuberculosis for evaluation of the response to chemotherapy: the effect on bacilli in the initial phase of treatment.

The purpose of this study was to develop and evaluate a guinea pig model of experimental airborne tuberculosis for its ability to assess chemotherapeutic regimens for their efficacy against virulent tubercle bacilli in vivo during the initial phase of treatment. The tissues examined included primary lung lesions and the metastatic foci in lung and spleen which result from the naturally occurring bacillaemia. The treatments examined, INH + RIF, INH + EMB, EMB + RIF, were initiated 4 weeks after infection and were continued for 8 weeks. Although minor differences were observed in the time of onset of a significant bactericidal effect or in the rate of decline in the microbial population, all three treatment combinations resulted in a significant reduction in the number of M. tuberculosis H37Rv recovered from primary lung lesions, primary lesion-free lung lobes and spleen. X-rays taken of excised inflated lung lobes showed a relationship between the degree of calcification of primary lung lesions and the number of surviving bacilli.

Animals

Bilateral papillitis with anti-neutrophil cytoplasmic antibodies associated with coeliac disease.

A 39 year old woman with untreated coeliac disease presented with some of its complications and bilateral papillitis. She was found to have antineutrophil cytoplasmic antibodies (ANCA) in high titres. Following institution of gluten-free diet the complications resolved. The papillitis, however, persisted and needed a course of prednisolone to resolve, and a fall in the ANCA titres was noted. We believe that this is the first report of an association of coeliac disease and ANCA.

Adult

The protective and allergenic potency of four BCG substrains in use in China determined in two animal models.

The objective of this study was to compare four BCG substrains from regional centres in China with BCG-Copenhagen 1331 (Danish strain) for protective and allergenic potencies. The comparisons were made in two different guinea pig models: one, a rational animal model involving aerosol challenge with 5-10 cfu Mycobacterium tuberculosis (strain H37Rv), and the other an animal model involving subcutaneous challenge with 250 cfu of H37Rv. For either model, the degree of protection was judged by quantitation of the number of H37Rv which could be recovered from the spleen. The results revealed: The allergenic potency of BCG-Shanghai and BCG-Beijing, substrains developed from the Danish strain, were comparable to that of the Danish vaccine. BCG-Lanzhou was significantly less allergenic and BCG-Chanchun, developed from BCG-Japan 172, was devoid of allergenic activity. Based on the number of H37Rv recovered from the spleen of guinea pigs killed 5 weeks after aerosol challenge, the protective effect of BCG-Shanghai and BCG-Beijing were comparable to that of the Danish vaccine. BCG-Lanzhou was of intermediate potency and BCG-Chanchun was devoid of protective activity. Based on the number of H37Rv recovered from the spleen of guinea pigs in the subcutaneous challenge group, the protective effects of BCG-Shanghai and BCG-Beijing were comparable to that of the Danish vaccine; BCG-Lanzhou was only slightly less potent, and BCG-Chanchun was devoid of protective activity. Good agreement was observed between the two animal models with respect to the protective potency of BCG vaccines.

Animals

Sudden death during ambulatory monitoring.

Three patients with ischaemic heart disease died suddenly while being monitored with an ambulatory tape recorder. Two had terminal ventricular fibrillation initiated by paired bidirectional ventricular ectopic beats against a background of scattered ectopic activity; both had had ventricular tachycardia during routine treadmill exercise testing in the week before death. The third patient developed bizarre ventricular complexes followed by asystole. Sudden death may be due to ventricular fibrillation initiated by paired ventricular ectopic beats with changing morphology, or asystole following bizarre ventricular complexes. Exercise testing may have an important predictive value.

Aged

Physical activity and the circadian rhythm of blood pressure.

1. Ambulatory blood pressure monitoring was carried out in 10 subjects for a period of 48 h, the first or second 24 h part of which was selected randomly to be a period of complete bed rest. 2. Heart rate was significantly lower throughout the period of bed rest except for the period 04.00-08.00 hours, when there was little difference. 3. The circadian variation of blood pressure was reduced during the day of bed rest but this was mainly due to higher night-time pressures.

Adult

Effect of labetalol on continuous ambulatory blood pressure.

1 The hypotensive action of labetalol was evaluated during 24 h by continuous intra-arterial ambulatory monitoring in 14 patients. The dose used ranged from 300--1800 mg daily. 2 The drug caused a significant reduction of systolic BP in 19 and diastolic BP in 20 of the 24 h of monitoring. Heart rate was also reduced but less markedly than BP. 3 The rapid early morning increase in BP was also effectively controlled. 4 The mild pre-waking increase in BP was not significantly reduced. 5 Labetalol treatment reduced the variation in systolic BP from the lowest observed quarter-hourly mean as compared with pre-treatment values. 6 The quarter hourly mean values were consistently smooth and revealed no sudden variations which might have resulted from postural hypotension.

Adult

Effect of labetalol in hypertension during exercise and postural changes.

1 Fourteen hypertensive patients were studied by intra-arterial BP monitoring to quantify the effects of standardized physiological stresses: Valsalva manoeuvre, isometric, treadmill and bicycle exercise, and 60 degree tilting before and after labetalol treatment. 2 The dose of labetalol ranged from 100--600 mg three times daily and the response was judged on outpatient clinic recordings. 3 The drug produced a sustained reduction of BP and heart rate responses during dynamic exercise and the Valsalva manoeuvre, but the degree of change from the lowered baseline were not changed by labetalol. The fall in BP on cessation of exercise was decreased rather than increased. 4 The response to controlled isometric muscle contraction was affected in a similar fashion. 5 Tilting produced a fall in BP after treatment, and this was most marked in those patients on the highest doses. However, compensatory increases in diastolic BP were observed.

Blood Pressure

Application of ion-exchange and lipophilic-gel chromatography to the purification and group fractionation of steroidal spirolactones, isolated from biological fluids.

Chromatography of steroidal spirolactones on DEAE-Sephadex A-25 under selected pH conditions allowed efficient separation of these compounds from other steroids and many of the endogenous components of human urine. The spirolactones were recovered in high yield, mostly over 90%. Lipophilic-gel chromatography provided a useful method for group fractionation of mixtures of these spirolactones with high recoveries (generally over 90%), unaffected by the presence of endogenous material from normal human urine.

Canrenoic Acid

Blood pressure circadian rhythm in essential hypertension.

1. Both systolic and diastolic blood pressure show a well defined circadian variation in ambulatory hypertensive subjects. 2. Blood pressure is highest in the mid-morning (10.00 hours) and lowest during sleep at 03.00 hours. 3. Treatment with oxprenolol (taken during the day) reduces daytime blood pressure but is less effective during the night and early morning.

Adult