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Biomedical subjects

R E Wilson

Publications and source records attributed to R E Wilson.

At least 127 records · Page 7Linked to original sources

Calmodulin in dispersed human parathyroid cells.

We investigated the presence and several of the properties of calmodulin in human parathyroid cells. Boiled extracts of such cell preparations contained a heat-stable factor causing a 2- to 3-fold calcium-dependent stimulation of calmodulin-deficient phosphodiesterase activity, which was parallel to that due to pure porcine calmodulin. This activation could be totally blocked by 10(-4) M trifluoperazine, with half-maximal inhibition at 3 X 10(-5) M, similar to the effects of this phenothiazine on porcine calmodulin. These results suggested the presence of calmodulin in human parathyroid cells. By comparison with known quantities of porcine calmodulin, human parathyroid cells contained 9-208 ng calmodulin/10(6) cells. The content of calmodulin in 3 normal parathyroid glands [65 +/- 8 (+/- SEM) ng/10(6) cells] did not differ significantly from that of 12 adenomas (61 +/- 16 ng/10(6) cells). Cells from 7 glands showing secondary hyperplasia, however, had significantly greater levels of calmodulin (164 +/- 11 ng/10(6) cells) than either normal cells or adenomas (P less than 0.001 and P less than 0.005, respectively). Extracts of human parathyroid cells caused half-maximal stimulation of phosphodiesterase activity at 1.1-4.8 microM free calcium. The concentrations of calcium half-maximally activating phosphodiesterase (Ka) did not differ significantly for normal or abnormal cells (3.3 +/- 0.03 vs. 2.6 +/- 0.33; P greater than 0.3). Moreover, in 2 cases in which normal parathyroid tissue was obtained from patients with adenomas, the Ka values for calcium for the normal and abnormal cells were similar (3.3 vs. 2.5 and 3.4 vs. 2.5 microM, respectively). Finally, there was no significant correlation between either the content of calmodulin or the Ka for calcium and the set-point for calcium [the calcium concentration causing half-maximal inhibition of parathyroid hormone (PTH) release] or the maximal rate of PTH secretion for dispersed parathyroid cells. These results suggest that human parathyroid cells contain calmodulin, but provide no evidence for a role of this protein in the abnormal calcium-regulated PTH release in hyperparathyroidism.

3',5'-Cyclic-AMP Phosphodiesterases↗

Analysis of recurrence patterns following curative resection for carcinoma of the colon and rectum.

The records of 525 patients with adenocarcinoma of the colon and rectum were reviewed. Two hundred and eighty-five patients were evaluable following complete curative resections. These patients were evaluated for patterns of recurrence. The over-all recurrence rate was 78 of 285, 27 per cent. The over-all recurrence rate by site was 24.0, 10.0, 11.5 and 35.0 per cent for the right, transverse and left colon, the sigmoid and the rectum, respectively. The over-all failure rate by stage was 13 per cent for Stage A, 11 per cent for Stage B1, 32 per cent for Stage C1, 37 per cent for Stage B2-3 and 56 per cent for Stage C2-3. The over-all failure rate as related to Stages A, B1, C1, B2-3 and C2-3 and to site of primary disease was: right--zero, 9, 33, 28 and 43 per cent, sigmoid--11, 15, 40, 52 and 62 per cent; rectal group--29, 14, 40, 46 and 60 per cent as related to respective stages. There was one failure among the five patients with Stage B2-3 disease in the transverse group and two failures among the nine patients with Stage B2-3 and one failure in the one patient with Stage C2-3 within the left colon group. Individual types of failure were compiled. Lesions involving the rectum and sigmoid colon had a significant local-regional component to relapse. Tumors of the right, transverse and the left colon had a significant distant recurrence rate. Factors of primary site, age at diagnosis, extent of disease and histology were reviewed as to the over-all recurrence and specific failure sites. From this analysis, a schema involving patterns of failure as related to primary site and stage within the colon, rectum and sigmoid were developed.

Adenocarcinoma↗

Successful treatment of metastatic sarcomas with cyclophosphamide, adriamycin, and DTIC (CAD).

Fifty consecutive adults with sarcoma were treated with Adriamycin (45 mg/m2) on day 1, cyclophosphamide (500 mg/m2) on day 2, and DTIC (400 mg/m2) on days 1 and 2 (CAD). Of the 23 patients with measurable metastatic disease, 4 patients (17%) had a complete response, 9 patients (39%) had a partial response, 5 patients (22%) had stabilization, but 5 patients (22%) did not respond. The actuarial survival of complete and partial responders was 31.5 months compared to 5.5 months for non-responders (P < .005). Chemotherapy doses were escalated to a median lowest white count of 700 cells/mm3. Acute gastrointestinal toxicity and alopecia occurred in all patients. CAD differed from previously reported combinations by omission of vincristine, a two-day dose schedule and dose rate intensification. CAD is recommended for patients with metastatic sarcoma.

Adult↗

The use and limitations of serial plasma carcinoembryonic antigen (CEA) levels as a monitor of changing metastatic liver tumor volume in patients receiving chemotherapy.

Nine patients with liver-predominant or liver-only metastatic adenocarcinoma, who received hepatic intra-arterial and peripheral intravenous chemotherapy, were evaluated to determine if changes in plasma CEA accurately indicated changes in liver tumor volume as estimated from serial liver scan defect sizes, and if the two were quantitatively related. When selected periods of tumor remission or progression were studied during chemotherapy, the index of change of serial CEA values correlated positively (r = 0.764, P = 0.01) with the index of change of liver tumor volume in all 9 cases. Changes in absolute CEA values, however, aid not correlate significantly with changes in absolute liver tumor volumes when assessed either during these selected periods or throughout individual patient courses. Biologic and methodologic factors that influence the quantitative relation between liver tumor volume and plasma CEA are discussed.

Adenocarcinoma↗

Patterns of recurrence following curative resection of adenocarcinoma of the colon and rectum.

This study explores the patterns of recurrence after "curative" operation for colorectal cancer. For an 11-year period, 1960-1971, 281 evaluable patients were resected at the Peter Bent Brigham Hospital. Crude five-year survival in these patients was 49%, but only 10% of those with recurrence lived five years. A total of 69 patients relapsed during their lifetime and 34 additional patients were found to have metastases at death. The initial site of metastases were regional in 23 patients (33%) and distant in 32 (46%). Simultaneous regional and distant metastases were found in 13 (19%) for a total of 65% of patients having initial distant metastases. Approximate recurrence rates by site were: 30% for sigmoid and rectum, 20% for right colon, and 10% for transverse and left colon. Tumor size was a significant determinant of recurrence but did not select for regional or distant sites. Recurrence by Astler-Coller modification of the Dukes-Kirklin classification revealed 10% for A + B1, 33% for B2, 35% for C1, and 50% for C2. More than half of the patients with distant metastases (18/32) had solely hepatic metastases yet the total incidence of liver metastases as the initial site was only 8% of the total. In general, the site of the primary cancer was the most important determinant of the type of recurrence; the stage and site of the primary tumor were most predictive for eventual relapse.

Adenocarcinoma↗

Morbidity and mortality after surgery in patients with disseminated or locally advanced cancer receiving systemic chemotherapy.

All postoperative complications and mortality were analyzed in a diverse group of patients operated upon by the authors during a ten-year period. These patients shared only two common factors: 1) known locally advanced or disseminated cancer, and 2) systemic chemotherapy within three weeks (either pre- or postoperatively) of major surgery. One hundred eighty-six operations were performed on 175 patients. The overall mortality in this series was 2.2% (four patients), with a complication rate of 5.9% (11 patients). Despite the known detrimental effects of widespread cancer and cytotoxic agents on wound healing, appropriate surgical intervention can be accomplished with an acceptable mortality and morbidity in patients with locally advanced or disseminated cancer who are receiving systemic chemotherapy.

Adolescent↗

Dose response of 1,2-dimethylhydrazine and methylazoxymethanol acetate in the F 344 rat.

Weanling male and female F 344 rats were given various doses of 1,2-dimethylhydrazine (DMH) or methylazoxymethyl acetate (MAMAc), and were then held for 46-64 weeks in an effort to determine a dose response and establish a dose level which would produce a low level of intestinal neoplasia with a minimal number of tumors in other organs. DMH proved superior to MAM in this respect, although liver lesions were still observed with both compounds at the lowest carcinogenic intestinal dose.

Animals↗

Modification of in vitro and in vivo immune function by acute inflammatory cells.

The ability of adoptively transferred, syngeneic polymorphonuclear leukocyte-rich (PMNLr) inflammatory cells to influence lymphocyte-mediated cytotoxicity (LMC), complement-dependent cytotoxicity (CDC), and skin allograft survival was studied in a murine model. BALB/c mouse PMNLr, stimulated by i.p. injection of either glycogen (G/PMNLr) or thioglycollate (T/PMNLr), were transferred to other BALB/c mice at the time of primary or secondary immunization with a cellular alloantigen (C57BL/6 spleen cells) or after skin allografting (C57BL/6 tailskin). The metabolic activity of each PMNLr population was determined by measuring glucose utilization in the hexose monophosphate shunt. It appeared that metabolic activity of the T/PMNLr was significantly greater than that of the G/PMNLr. Our results indicate that, while the infusion of G/PMNLr tended to suppress the primary cell-mediated immune response and the secondary humoral immune response, the infusion of T/PMNLr stimulated both of these responses. Furthermore, i.p. infusion of mice with G/PMNLr at a time approximating grafting resulted in prolonged graft survival, but neither T/PMNLr nor syngeneic thymocytes effect graft survival. Our data demonstrate that both cellular and humoral immunity can be modified by acute inflammatory cells. The metabolic status of the acute inflammatory cells seems to be critical in determining their immunoregulatory potential.

Animals↗

Pigment mutants of Chlamydomonas with deformed plastids and increased levels of chloroplast nucleic acids.

The chloroplast ultrastructure of two Chlamydomonas reinhardtii pigment variant mutants, U3N and U3A, is strikingly different from that of the wild type. The mutant chloroplast has greatly lowered levels of chlorophyll a and b, and lacks the usual ordered thylakoid membrane structure. The amount of chloroplast ribosomes is increased, but the pyrenoid and surrounding starch grains appear to be unaltered. Our biochemical analyses have shown that, while the properties of chloroplast DNA, ribosomal RNA, and ribosomes in these mutants appeared to be normal, their relative amounts per cell increased markedly when compared to the wild type. In U3N these increases were approximately 60% for chloroplast DNA and 80% for chloroplast ribosomes. However, the ratio of chloroplast rDNA genes to total chloroplast DNA remained unchanged as shown by DNA-rRNA hybrdization. We propose that (1) The enhanced level of chloroplast ribosomes in these mutants is a direct consequence of the elevated amount of chloroplast DNA. Both of these increases may, in turn, arise from defective mechanism for their control. (2) These mutants grow successfully in the absence of functional photosynthesis, provided an external carbon source is available to them, but functional plastid DNA, ribosomes and protein synthesis may still be a requirement for normal starch metabolism.

Chlamydomonas↗

Malignant intestinal obstruction.

The records of 66 consecutive patients who developed intestinal obstructions after treatment for cancer were reviewed. Approximately one third of the patients were found to have a benign cause of obstruction. The chances that an obstruction was due to cancer were increased if the patient had known metastatic cancer, previous colorectal cancer, if the primary was an advanced stage, and if the interval since treatment of the primary was short. Incomplete obstructions were treated with nasogastric suction. Although resolution of the obstruction on nasogastric suction without operation occurred in 24% of the admissions, 41% of those patients had to be readmitted for surgical relief of recurrent intestinal obstruction. Resolution of an obstruction on nasogastric suction occurred early, and there was little point in continuing a trial of suction for longer than 3 days.

Adolescent↗

Relationship of intestinal obstruction to serial plasma carcinoembryonic antigen levels.

Since it has been suggested that colonic obstruction due to carcinoma may play a role in elevations of circulating carcinoembryonic antigen, serial plasma carcinoembryonic antigen levels were studies in 19 patients with intestinal obstruction due to tumor and nontumor causes. Regardless of cause, eight of ten patients with colonic obstruction did not show decreased carcinoembryonic antigen levels after decompression. Two patients with postoperative carcinoembryonic antigen reductions of greater than 40 per cent had ascite removed at operation. Removal of a large volume of carcinoembryonic antigen-rich ascites was thought to contribute to the fall in circulating carcinoembryonic antigen. Six patients with small intestinal obstruction and one patient with large and small intestinal obstruction did not show a reduction in postdecompression carcinoembryonic antigen levels. One patient with Crohn's disease who underwent ileal resection and one with intestinal obstruction due to carcinoma of the ovary who underwent resection at the time of decompression had a greater than 40 per cent reduction in postoperative carcinoembryonic antigen levels. Inflamed intestinal and carcinoma of the ovary are known sources of carcinoembryonic antigen and their removal could explain the decrease in carcinoembryonic antigen. Rehydration, as monitored by plasma osmolality and protein concentration, did not explain changes in plasma carcinoembryonic antigen. Thus, it appears that carcinoembryonic antigen production may play a more significant role in the regulation of circulating carcinoembryonic antigen than the physiopathologic processes associated with obstruction.

Aged↗