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Biomedical subjects

R A Malt

Publications and source records attributed to R A Malt.

At least 145 records · Page 8Linked to original sources

Lost mass and excretion as stimuli to parabiotic compensatory renal hypertrophy.

To help determine the roles of lost renal mass and lost excretory ability in producing renoprival hypertrophy, observations were made in otherwise normal rats cross-circulated for 24 h with rats prepared in one of the following ways: bilateral nephrectomy, bilateral ureteral ligation, or bilateral nephrectomy with 24 h of uremia. Bilateral nephrectomy produced parabiotic increases in renal mass and in the average cellular concentration of RNA: bilateral ureteral ligation did not. Uremia did not potentiate the effects of bilateral nephrectomy. Lost mass is the determinant of compensatory renal hypertrophy.

Animals↗

Onset of cell proliferation in the shortened gut. Colonic hyperplasia after ileal resection.

Cytokinetics in colonic mucosa were studied after ileal resection in young female rats. The RNA content of the transverse colon was increased 32% after 7 days; after 14 days the increase was present throughout the colon. The DNA content of the ascending colon increased 29% after 10 days. Specific activity of DNA labeled with [3H-methyl]thymidine was elevated 29% in the ascending colon and elevated 49% in the descending colon on the 7th postoperative day. Colonic cell proliferation is stimulated within 1 week of ileal resection.

Animals↗

Onset of cell proliferation in the shortened gut. Rapid hyperplasia after jejunal resection.

Early manifestations of cell proliferation were studied in the large and small bowel of young female rats after resection of the proximal one-third of the small bowel. On the 2nd day after resection, the absolute amounts of RNA and DNA increased in gut distal to the resection. As compared with values from sham-resected gut, nucleic acid levels in much of the distal small bowel and colon increased. Increased specific activity in DNA after injection of [3H]thymidine was present in the small bowel on the 2nd day. Changes were marked and persistent in midgut for 10 days, tending to be less intense and of shorter duration in segments progressively more distal. Compensatory cell proliferation in midgut occurs within 2 days of jejunectomy.

Animals↗

Compensatory postresectional hyperplasia and starvation atrophy in small bowel: dissociation from endogenous gastrin levels.

Because exogenous gastrin has been implicated as a tropic hormone for mucosal cells of the intestinal tract and as a regulator of mucosal growth, we studied the effects on the gut of endogenous 23-fold variations of serum gastrin produced by various gastric operations. These were pyloroplasty, vagotomy and pyloroplasty, antrectomy, and fundectomy. After jejunal resection, RNA content, DNA content, incorporation of [3H]thymidine into DNA, crypt depth, and villus height in midgut and ileum were independent of gastrin levels. Loss of RNA and DNA during starvation was not prevented by high endogenous concentrations of serum gastrin, and DNA specific activity was not affected. Tropic effects distal to the duodenum produced by exogenous gastrin and pentagastrin may be results of supranormal levels.

Animals↗

Management of carcinoid tumors of the gastrointestinal tract.

Sixty-five patients seen at the Massachusetts General Hospital between 1951 and 1974 with carcinoid tumors of the gastrointestinal tract are reviewed. Sixty-two patients were operated upon, and only one carcinoid was discovered for the first time at autopsy. Although corrected actual five and ten year survival rates of more than 60% were attained, only one of 15 patients was alive five years after the discovery of liver metastases. Patients less than 60 years of age, with tumors of less than 0.5 centimeter in diameter and with no history of weight loss, survived best. Most rectal and appendiceal carcinoids were small, and there were no deaths in patients who had undergone local resection. Only 33% of the patients with small intestinal carcinoids survived for five years; none survived for more than one year after diagnosis of the carcinoid syndrome was made. All colonic carcinoids had metastasized by the time the operation was performed. Carcinoids of less than 0.5 centimeter in diameter located anywhere in the gastrointestinal tract can be managed by simple local resection. Tumors 1 centimeter in diameter warrant consideration of a more extensive operation. A radical excision usually is required for tumors of more than 2 centimeters in diameter, even in the presence of metastatic disease.

Adenoma↗

Appraisal of the treatment of carcinoma of the anus and anal canal.

Anal bleeding and pain were the symptoms in half of 53 patients with carcinoma within and around the area of the anus treated from 1950 to 1974. Twenty-seven carcinomas were exclusively located in the anal canal and six, in the perianal skin. Vaginal invasion was present in 13 of the women. There were 39 squamous cell carcinomas and nine basaloid cell carcinomas. More than 37 of the patients had an abdominoperineal resection as part of the treatment. The resection margins were positive for carcinomas in 11 patients. Radiation as the primary treatment was used only once. Palpably enlarged inguinal lymph nodes were treated by subsequent radical groin dissection. The crude over-all survival rate was 42 per cent; the adjusted five year survival rate was 38 per cent. Significant correlates of death were symptoms for longer than six months' duration bleeding, inguinal adenopathy and presence of hemorrhoids. In general, abdominoperineal resection is the operation of choice for carcinoma of the anal verge or anal canal. Inguinal lymphadenectomy at a later time should be reserved for patients with signs of metastases to the inguinal nodes.

Adenocarcinoma↗

Accumulation and decay of messenger ribonucleic acid in mouse kidney.

The stability of polyadenylated messenger ribonucleic acid(mRNA) from cytoplasmic structures sedimenting faster than 40S was analyzed in normal mouse kidney. Incorporation of radioactivity into poly(A)-containing and poly(A)-lacking cytoplasmic RNAs separated by oligo(dT)-cellulose chromatography was determined after sedimentation of RNA IN SODIUM DODECYL SULFATE CONTAINING SUCROSE DENSITY GRADIENTS. Radioactivity accumulated in poly(A)-containing RNA during the first 6 h and then decayed exponentially. Beginning 8-12h after administering label, two components were evident in the decay curve of poly(A)-containing RNA; the short-lived component (approximately 57% of newly synthesized molecules) had an apparent half-life of 6h, and the second class (approximately 43% of new mRNA) was more stable, decaying with a 24-h half-life. These studies provide the basis for examining the regulation of mRNA stability during compensatory renal hypertrophy.

Animals↗

Physical aspects and cytoplasmic distribution of messenger RNA in mouse kidney.

As a prerequisite to examining mRNA metabolism in compensatory renal hypertrophy, polyadenylated RNA has been purified from normal mouse kidney polysomal RNA by selection on oligo(dT)-cellulose. Poly(A)-containing RNA dissociated from polysomes by treatment with 10 mM EDTA and sedimented heterogeneously in dodecyl sulfate-containing sucrose density gradients with a mean sedimentation coefficient of 20 S. Poly(A) derived from this RNA migrated at the rate of 6-7 S RNA in dodecyl sulfate-containing 10% polyacrylamide gels. Coelectrophoresis of poly(A) labeled for 90 min with poly(A) labeled for 24 h indicated the long-term labeled poly(A) migrated faster than pulse-labeled material. Twenty percent of the cytoplasmic poly(A)-containing mRNA was not associated with the polysomes, but sedimented in the 40-80 S region (post-polysomal). Messenger RNA from the post-polysomal region had sedimentation properties similar to those of mRNA prepared from polysomes indicating post-polysomal mRNA was not degraded polysomal mRNA. Preliminary labeling experiments indicated a rapid equilibration of radioactivity between the polysomal and post-polysomal mRNA populations, suggesting the post-polysomal mRNA may consist of mRNA in transit to the polysomes.

Adenine↗

Short-lived methylated messenger RNA in mouse kidney.

In experiments originally designed to examine selective turnover of methylated "caps" in renal mRNA, we observed that [3H]methyl label decayed from mRNA containing poly(A) with a half-life of 1-2 hr. (Caps are blocked, methylated mRNA sequences of the general structure m7GpppNm p(1 or 2)Np.). To distinguish between metabolism of short-lived mRNA and discriminate turnover of "caps", we compared residual [3H]methyl label in 5' and 3'mRNA fragments prepared from mRNA isolated during the decay period. Hydrolysis of mRNA at 0 degrees with dilute KOH before oligo(dT)-cellulose selection produced 5' mRNA fragments enriched with an alkali-resistant oligonucleotide with a -5 charge; the 3' mRNA fraction was correspondingly reduced in oligonucleotide content. Since methyl label disappeared at the same rate from both fractions, we conclude that mouse kidney contains short-lived mRNA and that the "caps" of these labile mRNAs turn over with the rest of the mRNA molecule.

Animals↗

Conservation of ribosomal RNA during compensatory renal hypertrophy. A major mechanism in RNA accretion.

After removal of one mouse kidney, compensatory hypertrophy in the remaining kidney is marked in 2 days by a 20% average increase in ribosomal RNA (rRNA) per cell. Both 28S and 18S RNA are conserved during the initial stages of compensatory renal hypertrophy to an extent sufficient to account for the rest of the observed accumulation of rRNA. Like some cultured cells, the kidney conserves rRNA during physiological growth.

Animals↗

Risks in therapeutic portacaval and splenorenal shunts.

Analyses of the records of 120 patients who underwent portacaval shunting (PCS, 57%) or splenorenal shunting (SRS, 43%) from 1966-1973 disclosed that patients in each group undergoing elective shunts had the same preoperative physical condition and postoperative mortality rates (approximately 20%). Although the post-operative death rate from emergency shunts was 48%, patients having these procedures were poorer risks. Long-term incidences of encephalopathy were the same, irrespective of the type of shunt (PCS, 46%; SRS 36%, P greater than 0.5). Despite comparisons of data most unfavorable for PCS, 5-year survival rates were also the same after either type of shunt (all PCS, 29 +/- 7.5%, SRS, 42.0 +/- 7.4%, P = 0.23). The survival rate after elective PCS was also the same as after SRS during the entire 5-year period. However, the survival after all elective PCS and SRS was significantly greater than after emergency PCS (P range = 0.005-0.038); the poorer results of emergency shunting could be partly attributed to the poorer condition of patients selected. A numerical score based on serum bilirubin concentrations, ascites, and urgency of shunting reliably predicts postoperative mortality. Long-term encephalopathy is predicted by a history of encephalopathy and the urgency of shunting.

Adult↗