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Biomedical subjects

N Kumar

Publications and source records attributed to N Kumar.

At least 415 records · Page 23Linked to original sources
PubMed1981

Taxol-induced polymerization of purified tubulin. Mechanism of action.

Incubation of tubulin with taxol resulted in the assembly of tubulin in the absence of microtubule associated proteins. Optimum assembly occurred at approximately equal concentrations of tubulin and taxol. Both podophyllotoxin and colchicine inhibited the taxol-induced tubulin polymerization. Microtubules formed with taxol were also resistant to podophyllotoxin-induced depolymerization. The rate of tubulin subunit exchange into taxol-induced microtubules at steady state was 5-fold lower than into microtubule-associated protein (MAP2)-stimulated microtubules. There was a marked difference in the kinetics of tubulin polymerized in the presence of both taxol and MAP2 as compared to that obtained with either of them alone. In binding experiments, no competition was observed between taxol and MAP2 or the anti-tubulin drugs, e.g. colchicine, podophyllotoxin, and vinblastine.

Alkaloids↗
PubMed1981

Preferential action of a brain detyrosinolating carboxypeptidase on polymerized tubulin.

A carboxypeptidase purified from brain catalyzes the release of COOH-terminal tyrosine without further digesting tubulin. It is distinct from previously described carboxypeptidases, and appears to have specificity for tubulin as it is not inhibited by peptides and proteins with COOH-terminal tyrosine, and because, unlike carboxypeptidase A (which by removing tyrosine from aldolase causes its inactivation), this enzyme does not decrease aldolase activity. The enzyme detyrosinolates both self-assembly-competent (cycle-purified) and -incompetent (phosphocellulose-purified) tubulin. However, under assembly conditions the rate was 2-3-fold higher for competent tubulin. Preincubation of assembly-competent tubulin with podophyllotoxin or colchicine resulted in a parallel concentration-dependent inhibition of tubulin polymerization and detyrosinolation. Similarly, when incompetent tubulin was induced to polymerize by preincubation with purified microtubule-associated protein 2 (an assembly-promoting protein) or taxol, the initial rate of its detyrosinolation increased 3-5-fold, and this increase was blocked if podophyllotoxin was also added along with microtubule-associated protein 2 or taxol during the preincubation. Oligomers induced by adding vinblastine to incompetent tubulin were also detyrosinolated more rapidly, and the stimulation was abolished by maytansine, which has been shown to disperse the vinblastine-induced oligomers. When polymerized and subunit fractions were separated after a steady state mixture had been partially digested with the carboxypeptidase, the former was found to have lost 2-3 times more COOH-terminal tyrosine. Although both polymer and monomer can be detyrosinolated by the enzyme, polymeric and oligomeric forms are the preferred substrates. Carboxypeptidase appeared to release tyrosine at the same rate from populations of short and long microtubules.

Animals↗
PubMed1981

Interaction of tubulin with phospholipid vesicles. I. Association with vesicles at the phase transition.

Purified soluble tubulin will interact with highly sonicated small unilamellar vesicles of dipalmitoyl phosphatidylcholine. This results in the leakage of a fluorescent dye, carboxyfluorescein, from the internal aqueous space of the vesicles at the lipid phase transition. The amount of dye leaked from the vesicles is determined by the tubulin to vesicle ratio and partial dye leakage reflects the uniform leakage of carboxyfluorescein from all of the vesicles. Once tubulin interacts with dipalmitoyl phosphatidylcholine vesicles at the phase transition, it is unavailable to interact with additional vesicles. This interaction represents the formation of stable tubulin-vesicle recombinants as shown by density gradient centrifugation. Such recombinants are only formed by interacting the protein with the vesicles at the lipid phase transition temperature. The interaction is insensitive to ionic strength (0.001 to 4 M NaCl) and the recombinants remain stable for days.

Animals↗
PubMed1981

Interaction of tubulin with phospholipid vesicles. II. Physical changes of the protein.

We have shown that soluble tubulin will bind to small unilamellar vesicles of dipalmitoyl phosphatidylcholine (Klausner, R. D., Kumar, N., Weinstein, J. N., Blumenthal, R., and Flavin, M. (1981) J. Biol. Chem. 256, 5879-5885). This association uniquely occurs at the lipid phase transition. The tubulin, when bound to the vesicles, displays an altered tryptophan fluorescence characterized by a 5-nm blue shift in the emission maximum and a 22% decrease in fluorescence intensity, when compared to soluble tubulin. Tryptophans in vesicle-bound tubulin are less accessible to the aqueous collisional quenchers, acrylamide and iodide, than in soluble tubulin. Circular dichroism studies reveal an increase in alpha-helical content of tubulin as a result of vesicle interaction. Proteolytic digestion by trypsin of vesicle bound tubulin is slower than of soluble tubulin. The beta subunit of tubulin is preferentially protected from trypsin by vesicle interaction. Furthermore, the pattern of tryptic cleavage products is altered by this interaction.

Acrylamides↗
PubMed1981

The question of onymity and anonymity of a questionnaire in a drug use survey.

In a drug use survey of 457 final-year medical students a self-administered questionnaire included the controversial question whether such questionnaires should be onymous or anonymous. Definite answers either in favour of or against anonymity were given by 216 respondents. Of these, 72.2 per cent were in favour of anonymity, only 27.8 per cent favoured onymity. Among those who provided ambiguous answers, or who did not respond on the issue of anonymity vs. onymity, there were significantly more drug users. Where there was no family history of drug use, or where parents definitely disapproved of drug use, a high proportion of respondents were in favour of anonymity.

Anonyms and Pseudonyms↗
PubMed1980

Ovarian neoplasms resembling sex cord tumors with annular tubules.

A clinicopathologic analysis of 6 patients with ovarian neoplasms resembling sex cord tumors with annular tubules (SCTAT) was performed. The patients' ages ranged from 20 to 43 years. Most had signs and symptoms of estrogenic hormonal imbalance; none had evidence of the Peutz-Jeghers syndrome. The tumors were unilateral in all cases and, except for one lesion of microscopic size, were from 3 to 18 cm in greatest dimension. One tumor was combined with a germinoma. Surgery alone was the primary mode of therapy in all cases. Lymph nodal metastases developed in 2 patients 7.5 and 10.5 years postoperatively. They are the first documented examples of malignant behavior recorded. At the time of last known contact, all patients were alive without demonstrable tumor for intervals from 1.5 to 16.3 years (mean, 7.8 years) after initial treatment. While the annular patterns of growth have often been attributed to Sertoli cell differentiation, histologic and cytologic features of granulosa cell tumor were observed in areas of the primary tumors and in metastatic lesions. True lumen formation was never observed in the so-called tubules. We propose classification of SCTAT as a distinctive annular and membranous variant of granulosa cell tumor in view of the morphologic similarities and comparable clinical behavior of these two neoplasms.

Adult↗
PubMed1979

Early weight bearing in the treatment of fractures of the tibia.

The paper describes a simple and effective practical method of dealing with the fractures of the tibia by means of a long-leg walking plaster-of-Paris cast. The results are assessed in a series of 44 patients, 28 of whom were treated by early weight bearing, while the remaining 16 were treated by traditional closed methods. A simple system of grading tibial fractures is described in order to facilitate valid comparisons. The results conclusively show that the early weight bearing regime results in the fractures uniting in half the time of the late weight bearing series. Details of two cases in each grade of the early weight bearing series are given.

Adolescent↗