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Biomedical subjects

S Krishnamurthi

Publications and source records attributed to S Krishnamurthi.

At least 55 records · Page 3Linked to original sources
PubMed1986

Lack of inhibition of thrombin-induced rise in intracellular Ca2+ levels and 5-hydroxytryptamine secretion by 1-oleoyl-2-acetylglycerol in human platelets.

The effect of 1-oleoyl-2-acetylglycerol (OAG) on the thrombin-induced rise in intracellular Ca2+ levels ([Ca2+]i) and 5-hydroxy[14C]tryptamine ([14C]5HT) secretion was studied. In washed human platelets prelabelled with [14C]5HT and quin 2, OAG (10-50 micrograms/ml) induced no significant aggregation, [14C]5HT secretion or rise in [Ca2+]i in the presence or absence of fibrinogen. However, addition of OAG (10-50 micrograms/ml) 10 s to 5 min before or 10-60 s after addition of threshold concentrations of thrombin (less than 0.03 U/ml) resulted in a significant potentiation of aggregation and [14C]5HT secretion without any effect on the thrombin-induced rise in [Ca2+]i. Both EGTA, which abolished the latter and creatine phosphate/creatine phosphokinase, the ADP scavenger, totally inhibited the aggregation but only partially reduced [14C]5HT secretion in response to thrombin plus OAG. At higher concentrations of thrombin, neither the rise in [Ca2+]i nor the extent of [14C]5HT secretion was significantly altered by OAG addition. The results demonstrate that, unlike phorbol esters, OAG has no inhibitory effect on thrombin-induced [Ca2+]i mobilisation but can synergize with low concentrations of thrombin in potentiating [14C]5HT secretion even at basal [Ca2+]i.

Blood Platelets↗
PubMed1985

Studies on the effect of platelet inhibitors on platelet adhesion to collagen and collagen-induced human platelet activation.

The effect of pyridoxal 5'-phosphate (PALP) and trifluoperazine (TFPZ), the calmodulin antagonist, on in vitro platelet adhesion to collagen and collagen-induced platelet activation was studied using platelet-rich-plasma (PRP) or washed platelets (WPL). Platelet aggregation and [14C]-5HT release induced by "threshold" or low concentrations of collagen (0.6 micrograms/ml) in PRP were completely abolished by PALP (24 mM), TFPZ (250 microM) as well as indomethacin (10 microM). At higher concentrations of collagen (10-15 micrograms/ml) in PRP and WPL, the use of stirred and unstirred platelets treated with collagen enabled a distinction to be made between aggregation and adhesion-mediated release reaction. Platelet aggregation and the aggregation-mediated release reaction induced by these concentrations of collagen in stirred platelets were completely abolished by PALP, TFPZ and indomethacin although neither adhesion to collagen nor the adhesion-mediated release reaction of unstirred platelets was significantly affected by these inhibitors. Interestingly, both adhesion and the adhesion-mediated release reaction were abolished by concentrations of PALP 10-40 fold higher than those required to abolish aggregation. Collagen-induced platelet aggregation, but not platelet adhesion, was inhibited in resuspended platelets pretreated with PALP and NaBH4 indicating a separation in the membrane sites involved in aggregation and adhesion. The results further emphasize the distinction between adhesion and aggregation-mediated events with regards to collagen with the latter being more susceptible to inhibition by antiplatelet agents such as PALP and TFPZ.

Collagen↗
PubMed1985

Multimodal approach in the therapy of stage III female breast cancers.

One thousand thirty-seven female breast cancers were treated at the Cancer Institute (WIA), Madras, between 1965 and 1978. Five hundred twenty-one of them (ie, just over 50%) were in stage III, with extensive local disease, unsuitable for surgery ab initio. Four hundred twelve of them (group A) received radiation therapy (RT) initially and 109 (group B) a combination of radiation and chemotherapy (CT). In 68% of the former and 77% of the latter the tumours became resectable after this preliminary treatment. Radical mastectomy in group A and Patey's mastectomy in group B were performed. The material in these two groups was similar. The five-year survival NED in group A was 45%, and in group B 64.61%. Adequate surgery following RT and CT seemed essential to improve survival. The impact of added chemotherapy (CT) was mainly felt in the node-positive cases.

Adult↗
PubMed1984

Regulation of human platelet activation--analysis of cyclooxygenase and cyclic AMP-dependent pathways.

We have studied the regulation of human platelet activation by cyclic AMP (cAMP), and the cyclooxygenase products by examining the effect of prostacyclin (PGI2) and indomethacin on platelet aggregation, release reaction and thromboxane B2 (TxB2) generation induced by the full dose range of common platelet agonists in both platelet-rich plasma and washed platelets. Platelet aggregation, [14C]-5HT and TxB2 release induced by "threshold" and "supramaximal" concentrations of ADP, adrenaline, platelet-activating factor (PAF) and U46619 were totally abolished by low concentrations of PGI2 (3-6 nM). In contrast, platelet activation induced by submaximal concentrations of collagen, thrombin and the calcium ionophore A23187 was only partially inhibited by PGI2 (3-3000 nM). PAF-induced release reaction like that induced by ADP and adrenaline was totally dependent on the cyclooxygenase products and aggregation, while U46619-induced release reaction was only partially dependent on aggregation and the cyclooxygenase products. While both PGI2 (18-3000 nM) and indomethacin (10 microM) abolished collagen-induced aggregation and the aggregation-mediated release reaction, neither inhibitor significantly inhibited platelet adhesion or the adhesion-mediated release reaction. Maximal thrombin-induced aggregation and release reaction was also not significantly inhibited by PGI2 (300 nM) or indomethacin (10 microM). Thromboxane (TxB2) generation induced by sub-maximal to maximal concentrations of collagen, thrombin and A23187 was, although significantly inhibited, not abolished by PGI2. These results demonstrate that PAF is a "weak" agonist similar to ADP and adrenaline, U46619 is an agonist intermediate between weak and strong which induces a release reaction that is only partially dependent on aggregation, but unlike the strong agonists, is totally susceptible to inhibition by PGI2, PGI2 is an indirect inhibitor of phospholipase activation, which does not significantly inhibit non-aggregation-mediated arachidonate mobilization, induced by the strong agonists, and the so-called third pathway in the collagen and thrombin-induced release reaction, which is insensitive to indomethacin, is also insensitive to elevators of cAMP such as PGI2.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1984

The biological approach to the radiotherapy of the oral cancers of South India.

Two-thirds of all cancers in South India are squamous cell carcinomas, of which 78% to 93% are late cases requiring radiotherapy. Oral cancers, which constitute the majority of these, provided an excellent clinical model for studies in radiotherapeutic biology. Their characteristics made them ideally suited for our clinical trials. The paper reviews the special biology of these lesions, the factors involved in their radiation non-response, the therapeutic postulations that suggested themselves, the implementation of these therapeutic protocols and the mixed story of failure and success that has marked the two decades of these studies. It discovers the fact that radiation response is not just a factor of tumor extent but involves several biological subtleties in both tumor and its host environment. It also discusses possible future approaches to bridge a gap of about 30% failure in these lesions, especially in the context of a poor economy.

Bleomycin↗
PubMed1983

Irradiation, bleomycin and hyperbaric oxygen in the treatment of oral carcinoma.

The present report is the sixth in a series of combination therapy trials in oral carcinoma in South India conducted since 1960. In the fifth trial a combination of bleomycin (BLM) and irradiation was compared with irradiation alone. The results gained and the subsequent experience in an unselected series demonstrated in buccal mucosal squamous cell carcinomas a highly superior effect with the irradiation-BLM combination, but still revealed a failure rate around 30 per cent. The present clinical trial--irradiation + BLM was compared with irradiation + BLM + hyperbaric oxygen (HbO) and irradiation + placebo + HbO--was undertaken in an attempt to eliminate or at least reduce these failures. The results were unexpectedly disappointing in that the irradiation combined with BLM + HbO proved to be inferior to irradiation + BLM. An attempt has been made to elucidate the possible reasons for this surprising outcome.

Bleomycin↗
PubMed1983

Platelet activation during steady state sickle cell disease.

Previous reports have given conflicting conclusions of the role platelets may play in initiating vaso-occlusive sickle cell crisis. Seven patients homozygous for sickle cell hemoglobin, and seven age, race and sex matched controls were each studied on at least two occasions in a six week period of normal health. The number of platelets circulating as aggregates, the plasma concentration of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF-4) were significantly elevated compared with controls. These findings were confirmed with a second series of fourteen patients and nine controls. Patient's platelets in plasma adjusted for both platelet number and citrate concentration aggregated more in response to low concentrations (0.4 and 1 microM) but less to higher concentrations (4 and 20 microM) of ADP and needed significantly more prostacyclin (PGI2) to inhibit ADP induced aggregation than did platelets from control subjects. There was no significant difference in plasma concentration of fibrinopeptide A and thromboxane (Tx)B2, nor in the platelet generation of TxB2 and release of serotonin and beta TG induced by aggregating agents. Thus, the platelets of patients with sickle cell anemia in the steady state are readily activated and respond in vivo by increased formation of aggregates and release of beta TG and PF-4.

Adenosine Diphosphate↗
PubMed1982

Effect of pyridoxal 5'-phosphate (PALP) on human platelet aggregation, dense granule release and thromboxane B2 generation--role of Schiff base formation.

Pyridoxal 5'-phosphate (PALP) inhibited ADP, thrombin, adrenaline, PAF and AA induced aggregation and 14C-5HT release. Thromboxane B2 (TxB2) generation induced by all the above agents except AA was also inhibited indicating that PALP may be inhibiting AA release via phospholipase A2 activation rather than AA metabolism. PALP inhibited ristocetin induced aggregation in PRP and agglutination in formaldehyde-treated washed platelets (FWP). Inhibition of ADP, adrenaline, PAF and AA-induced aggregation and 14C-5HT release by PALP was found in resuspended platelets pretreated with PALP and sodium borohydride suggesting that inhibition was mediated by Schiff base formation with platelet surface amino groups. Irreversible fixation of PALP to the platelet membrane by borohydride reduction also inhibited thrombin induced 14C-5HT release and TxB2 generation but no thrombin induced primary aggregation or ristocetin induced agglutination in FWP. This suggests that PALP may interact with specific glycoproteins on the platelet membrane involved in ADP, adrenaline and PAF induced primary aggregation and that PALP could be inhibiting ristocetin induced agglutination by direct interaction with ristocetin or F VIII RCoF.

Alprostadil↗
PubMed1980

Combined bleomycin and radiotherapy in oral cancer.

A clinical trial comparing Bleomycin (BLM) plus radiation against radiation alone is reported. One hundred and fifty-seven previously untreated T3 and T4 and N0, N1 or N2 buccal squamous cell carcinomas were entered. Eighty-four of these received the combined therapy and 73 were controls. Cobalt-60 teletherapy using two opposing fields was employed. BLM was administered intra-arterially in 42 patients, intravenously in 22 patients and intramuscularly in 20 patients. The 73 controls received physiological saline as a placebo. Total clinical healing of the lesion within the volume of irradiation eight weeks after the end of radiotherapy was termed a favourable response. Anything else was a failure. Five-year recurrence-free rates and disease-free survival were also evaluated. The favourable response rate in the study group was 78.6% and in the control 19.1%. The corresponding recurrence-free rates and five-year survival rates were 71.8% and 17%, and 65.5 and 23.5% respectively. The main toxic features were acute mucositis, pneumonitis and dermatitis.

Bleomycin↗
PubMed1977

Combined therapy of oral cancer bleomycin and radiation: a clinical trial.

A concurrent randomised controlled clinical trial to evaluate a combination of Bleomycin and radiation as against radiation only in the treatment of advanced oral cancer has been conducted at the Cancer Institute, Madras, since 1971. All T3 and T4 previously untreated oral squamous cell carcinomas with N0, N1 and N2 regional nodes, or N3 nodes confined to the submandibular region, without systemic metastases or gross infiltration of the temporal and infratemporal fossa producing total trismus, and in decent general health were eligible for the trial. Patients with gross active pulmonary tuberculosis were excluded, as were recurrent carcinomas. Age, external fungation of growth or radiological bone invasion were no bar. Randomisation was done by the sealed envelope technique. The study group received concurrent fractionated cobalt 60 teletherapy using two opposing fields and 10-15 mg of Intra-arterial or Intravenous Bleomycin. The controls received fractionated cobalt teletherapy and i.v. or i.m. distilled water on the same protocol as the Bleomycin cases. All cases were evaluated double blind 8 weeks after the end of radiation therapy, and were classified as 'favourable response' or 'failure'. The criterion of 'favourable response' was 'total clinical healing of the tumour within the volume of irradiation with no subsequent recurrence within that volume, whatever the length of follow up'. Anything else was reported as a failure. A long term follow up of 3 years is also available. 136 cases have completed the trial. The favourable response in the study group was 77% as against 20.9% in the control group. The differential response is statistically significant. The present study is the fourth in the series of combined therapeutic trials conducted in advanced oral squamous cell carcinoma since 1958. (Krishnamurthi and Shanta, 1963, 1965, 1967 and 1971). A concurrent randomised controlled clinical trial to evaluate the combination of Bleomycin and radiation as against radiation only in treatment of advanced oral cancer has been conducted at the Cancer Institute, Madras since 1971.

Bleomycin↗
PubMed1976

Combined therapy in carcinomas of the female breast.

Of 606 female breast cancers treated, 364 of them in stage I, II and III, only 7 cases were in stage I. All stage II and III cases in good general condition received radical preoperative irradiation to the entire breast volume and the regional lymphatic areas over a period of 4 wk, followed 4 wk later by a radical mastectomy. No postoperative irradiation was administered. The biological basis of this therapeutic policy is explained in detail and the 5-yr disease-free survival of patients in relation to stage of disease, treatment method, histology of the primary tumor, histologic nodal metastatic status, postradiational status of the breast primary, the menstrual status of the patient, and the general metabolic status is discussed. It is explicitly shown by meticulous histological study of the breasts and the axillary lymph nodes removed at surgery that radical irradiation per se is inadequate to sterilize the breasts and that subsequent radical surgery is essential. Furthermore, two-thirds of the stage III cancers, which would have been considered inoperable by conventional criteria, were rendered operable by preoperative irradiation, with a near 50% 5-yr disease-free survival.

Adenocarcinoma↗
PubMed1976

Possible factors in remote metastases in female breast cancer.

The association of metastases (M) with age of patient, stage of disease, the gross and microscopic characteristics of the primary tumor, its physical location, the postradiational status of the breast, the extent and level of histological nodal involvement, the type of surgery practiced, and the host's biological environment are analysed. The authors conclude that the critical factor in systemic dissemination in female breast cancer is the extent and level of metastatic nodal involvement. Though the association between stage of disease, character of tumor (T), and histology are significant, the cruicial factor seems to be the nodal involvement. Systemic metastases are significantly higher in inner quadrant tumors. Possible methods of circumventing this dissemination are discussed.

Adult↗