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D D Patel

Publications and source records attributed to D D Patel.

At least 163 records · Page 9Linked to original sources

Isolation of cowpox virus A-type inclusions and characterization of their major protein component.

A-type inclusions (ATI)2 are large well-defined structures that appear in the cytoplasm during the late stages of the multiplication cycles of many poxviruses. The ATIs produced by the CPRC1 strain of cowpox virus in strain 143 human osteosarcoma cells have been isolated and characterized. These inclusions which can be recovered in large amounts (about 20 mg per 10(9) cells), appear to consist entirely of a single protein species that has a molecular weight of 160,000. It is a late protein, stable in infected cells, and during the late stages of the multiplication cycle it is one of the most abundantly synthesized proteins. Very similar ATIs composed of a serologically closely related protein of the same size are formed in cells infected with raccoonpox virus. In cells infected with vaccinia virus strain WR much smaller inclusions are formed; further, in such cells large amounts of a late protein with a molecular weight of 94,000 are produced that is also closely related to the cowpox virus ATI protein.

Cell Fractionation↗

The effect of mevalonate on 3-hydroxy-3-methylglutaryl-CoA reductase activity and the absolute rate of cholesterol biosynthesis in human monocyte-derived macrophages.

Normal monocyte-derived macrophages maintained in medium containing 20% whole serum exhibited a high activity of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase while expressing appreciable, but not maximal receptor-mediated uptake and degradation of low-density lipoprotein (LDL). Addition of extracellular mevalonate led to a concentration-dependent fall in both processes, although a higher concentration was required to produce the same effect on LDL degradation as on HMG-CoA reductase activity. The true rate of cholesterol synthesis by the cells was already high without mevalonate and was not further increased when the intracellular pool of mevalonate was expanded. After preincubation with lipoprotein-deficient serum receptor-mediated degradation of LDL was increased but HMG-CoA reductase activity was decreased. Both were more sensitive to extracellular mevalonate and a given concentration of mevalonate now produced the same percentage fall in LDL degradation and reductase activity. The amount of cholesterol synthesized by the cells was markedly reduced during incubation with lipoprotein-deficient serum, probably as a result of the decreased reductase activity compounded by a lack of endogenous substrate. If these were circumvented by adding mevalonate, cholesterol synthesis was restored to normal. These results suggest that the fall in HMG-CoA reductase activity during incubation with lipoprotein-deficient serum resulted from repression by some non-sterol product of mevalonate metabolism. They imply that the need for this product by cells growing in whole serum leads to a particularly high HMG-CoA reductase activity and could account for their apparent preference for endogenous synthesis of cholesterol rather than for receptor-mediated uptake of LDL.

Cholesterol↗

The absolute rate of cholesterol biosynthesis in monocyte-macrophages from normal and familial hypercholesterolaemic subjects.

The true rate of cholesterogenesis in cultured monocyte-macrophages was determined from the incorporation of [2-14C]acetate into cholesterol, using the desmosterol (cholesta-5,24-dien-3 beta-ol) that accumulated in the presence of the drug triparanol to estimate the specific radioactivity of the newly formed sterols. It was shown that this procedure could be successfully adapted for use with cultured monocytes despite the accumulation of other unidentified biosynthetic intermediates. In cells maintained in 20% (v/v) whole serum approx. 25% of the sterol carbon was derived from exogenous acetate. Cholesterol synthesis was as high in normal cells as in cells from homozygous familial hypercholesterolaemic (FH) subjects and accounted for 50% of the increase in cellular cholesterol. The addition of extra low-density lipoprotein (LDL) reduced cholesterol synthesis, apparently through a decrease in the activity of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase). When incubated in lipoprotein-deficient serum some cells did not survive, but those that remained showed a normal increase in protein content; the amount of cellular protein and cholesterol in each well did not increase and cholesterol synthesis was reduced by over 80%. HMG-CoA reductase activity fell less dramatically and the proportion of sterol carbon derived from exogenous acetate increased, suggesting that the low rate of cholesterogenesis with lipoprotein-deficient serum was due to a shortage of substrate. The results indicate that under normal conditions monocyte-macrophages obtain cholesterol from endogenous synthesis rather than through receptor-mediated uptake of LDL, and that synthesis together with non-saturable uptake of LDL provides the majority of the cholesterol required to support growth.

Acetates↗

The regulation of 3-hydroxy-3-methylglutaryl-CoA reductase activity, cholesterol esterification and the expression of low-density lipoprotein receptors in cultured monocyte-derived macrophages.

Human blood monocytes cultured in medium containing 20% whole serum showed the greatest activity of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and [14C]acetate incorporation into non-saponifiable lipids around the 7th day after seeding, the period of greatest growth. Although there was enough low-density lipoprotein (LDL) in the medium to saturate the LDL receptors that were expressed by normal cells at that time, HMG-CoA reductase activity and acetate incorporation were as high in normal cells as in cells from familial-hypercholesterolaemic (FH) patients. Both the addition of extra LDL, which interacted with the cells by non-saturable processes, and receptor-mediated uptake of acetylated LDL significantly reduced reductase activity and increased incorporation of [14C]oleate into cholesteryl esters in normal cells and cells from FH patients ('FH cells'), and reduced the expression of LDL receptors in normal cells. Pre-incubation for 20h in lipoprotein-deficient medium apparently increased the number of LDL receptors expressed by normal cells but reduced the activity of HMG-CoA reductase in both normal and FH cells. During subsequent incubations the same rate of degradation of acetylated LDL and of non-saturable degradation of LDL by FH cells was associated with the same reduction in HMG-CoA reductase activity, although LDL produced a much smaller stimulation of oleate incorporation into cholesteryl esters. In normal cells pre-incubated without lipoproteins, receptor-mediated uptake of LDL could abolish reductase activity and the expression of LDL receptors. The results suggested that in these cells, receptor-mediated uptake of LDL might have a greater effect on reductase activity and LDL receptors than the equivalent uptake of acetylated LDL. It is proposed that endogenous synthesis is an important source of cholesterol for growth of normal cells, and that the site at which cholesterol is deposited in the cells may determine the nature and extent of the metabolic events that follow.

Acetates↗

Effect of bleomycin-radiotherapy combination in management of head and neck squamous cell carcinoma.

Twenty-five patients with head and neck squamous cell carcinoma were treated with bleomycin-radiotherapy protocol, 15 mg bleomycin I.V. on alternate days followed by radiation within half an hour. The average total dose of bleomycin was 150 mg. Radiotherapy was given daily. Two patients were lost to follow-up very early in the course of the treatment and were removed from the study for statistical purposes. Thirty-six patients with head and neck squamous cell carcinoma who were treated with radiotherapy alone during the same period were used as controls. The patients were followed for two years. The incidence of response rate did not differ significantly between regimens; however the incidence of side effects with bleomycin-radiotherapy, 82.61%, is significantly more than that of radiotherapy alone (52.78%). Median survival time (MST) of those responding to bleomycin-radiotherapy protocol was seven months and 12 days and for radiotherapy responders was six months. Neither the response rate nor the MST improve significantly after pretreatment with bleomycin. On the contrary, the incidence of side effects increased significantly.

Adult↗

Carcinoma of the anterior tongue in adolescence.

Carcinoma of the oropharyngeal region is one of the most common malignant lesions seen in western India, comprising about 47% of all cases seen at the Gujarat Cancer and Research Institute. Of these, carcinoma of the tongue has the maximum incidence. In India the ratio between carcinoma of the anterior and posterior tongue is 33:66, the reverse of that published in Europe and America. The highest incidence of carcinoma of the anterior tongue appears in males 50 to 60 years of age; only 11 cases have been reported in patients under 20 years of age. From 1969 to 1974, 218 cases of carcinoma of the anterior tongue was seen at the M.P. Shah Hospital. This paper reports five cases of carcinoma of the anterior tongue found in patients under 20 years of age. Although the anterior tongue is a visible and approachable site, all five lesions were too advanced to cure. There did not seem to be any contributory factor to produce this malignant lesion at such a young age. The patients were all male, the youngest 11 years old. Two cases were treated with surgery; one also received postoperative radiotherapy. The remaining three cases were treated with palliative radiotherapy and chemotherapy. The pathology and the current view of management are discussed.

Adolescent↗

Evaluation of serum alkaline DNase activity in treatment monitoring of head and neck cancer patients.

Our previously published data on breast cancer suggest that serum alkaline DNase, a known circulating tumour marker, can be used for treatment monitoring of cancer patients. Serum alkaline DNase activities were analyzed in 215 untreated head and neck cancer patients. The enzyme activity ranged from 0.17 to 97.97 IKU/l in untreated cancer patients. Responders (n = 314) showed significantly elevated activity of alkaline DNase as compared to untreated cancer patients (p < 0.001). While non-responders (n = 168) showed comparable activity with untreated cancer patients. Serum alkaline DNase activities were significantly elevated in responders as compared to non-responders (p < 0.001). Our clinical studies during follow-up of patients indicated that the variations in serum alkaline DNase activities in individual patients correlate closely with response to therapy. Serum alkaline DNase also appeared to be useful in predicting treatment response in the long-term follow-up of patients. Serum alkaline DNase was systematically examined as a possible indicator for recurrence in patients under complete remission. In conclusion, serum alkaline DNase may be useful as a treatment monitoring in patients with head and neck malignancies.

Adolescent↗