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Biomedical subjects

R A Malt

Publications and source records attributed to R A Malt.

At least 37 records · Page 2Linked to original sources

Ménétrier's disease. A trivalent gastropathy.

Current conceptions of Ménétrier's disease only obliquely resemble those originally described. Bona-fide cases are so uncommon that, of 125 cases diagnosed as Ménétier's disease, hypertrophic gastritis, or protein-losing gastropathy treated at the Massachusetts General Hospital during the 26-year period of 1962-1987, only six cases merited an unequivocal anatomic diagnosis. Two other cases previously described proved on review to be nondiagnostic in one instance and Campylobacter pylori gastritis in the other. Because abnormalities in the secretion of gastric acid and in the loss of protein from the stomach may coexist, a representation of each case in semiquantitative terms can be described on triaxial coordinates. Three patients had a hypercoagulable state, one in association with gastric carcinoma. One other case of gastric carcinoma and one of esophageal carcinoma coexistant with Ménétrier's disease were identified. Administration of subcutaneous heparin during the perioperative period to patients with Ménétrier's disease is appropriate regardless of whether or not hypercoagulation or carcinoma is manifest. If treatment with anticholinergic drugs and inhibitors of gastric acid secretion fails, total gastrectomy is the best solution, because it stops protein loss, eliminates hyperchlorhydria, prevents development of gastric carcinoma, and permits anastomotic reconstruction between normal esophagus and normal small bowel.

Adult↗

N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide-induced bladder cancer in mice: augmentation by sutures through the bladder wall.

The augmenting effect of chronic inflammation on bladder cancer was studied in female Swiss mice treated with N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT), 0.15% by weight of diet for 20 weeks. To produce chronic inflammation one silk suture and one catgut suture were placed through the bladder wall of 63 mice to receive FANFT and 18 to receive normal diet. In remaining mice (no. = 62) the bladder was simply touched without suture insertion. Thirty-two animals treated with FANFT and 33 treated with FANFT + sutures also received supplements to their drinking water throughout the experiment of the sulfhydryl-reducing agent N-acetylcysteine (500 mg./kg. body weight/day). Seven weeks following FANFT treatment, bladder cancers developed in 12% of mice with sutures and FANFT and in 19% of those with sutures, FANFT, and N-acetylcysteine. No cancers developed in mice receiving FANFT alone or FANFT with N-acetylcysteine and none in mice treated with sutures only. Placement of silk sutures through the bladder wall of mice augments FANFT-induced bladder cancer. N-acetylcysteine at these doses does not influence the incidence.

Acetylcysteine↗

Augmentation of chemically induced pancreatic and bronchial cancers by epidermal growth factor.

The incidence of Syrian golden hamsters with pancreatic cancer induced by subcutaneous injections of N-nitroso-bis(2-oxopropyl)amine for 19 weeks (each 10 mg/kg) increased from 44% to 75% (p=0.016) when epidermal growth factor was also administered from week 5 through week 8 (5 mug energy three days for injections). Epidermal growth factor increased pancreatic weight and body weight. The incidence of animals with bronchial cancer doubled. Epidermal growth factor could be a cocarcinogen as a result of its mitogenic activity.

Animals↗

Regulation of ribosome synthesis during compensatory renal hypertrophy in mice.

Ribosomal synthesis was studied at the transcriptional and translational levels to investigate the mechanisms of ribosome accretion during compensatory renal hypertrophy. As measured by in vitro transcriptional runoff comparisons 6-48 h after surgery, nuclei from the kidney remaining after contralateral nephrectomy show an increase of up to 150% in the rate of synthesis of ribosomal precursor RNA. The rate of rDNA transcription is 40-50% greater than control values as early as 6 h after nephrectomy; by 48 h, the rate returns to normal. In contrast to the stimulated transcription of rDNA and accretion of rRNA, the steady-state levels and the cytoplasmic distribution of ribosomal protein mRNAs S16 and L10 remain unchanged during induced renal growth. Thus coordinate production of adequate protein for increased assembly of ribosomes during induced renal growth appears to be accomplished by increasingly efficient translation of existing ribosomal protein mRNAs or by post-translational stabilization of ribosomal proteins. The rate of rDNA transcription may be regulated by accelerating the transcription of already functioning genes or, more likely, by recruiting transcription units that are transcriptionally inactive in the normal kidney.

Amanitins↗

Fibrin deposition in autochthonous Syrian hamster pancreatic adenocarcinomas induced by the chemical carcinogen N-nitroso-bis(2-oxopropyl)amine.

Immunofluorescence studies have demonstrated the presence of fib (a group of fibrinogen- and fibrin-related proteins that react with antibodies raised against fibrinogen) in the stroma of several transplantable animal and autochthonous human tumors. Acceptance of these reports was tempered by the possibility of artifactual clotting and fibrinolysis associated with tumor removal or tumor transplantation and by the relatively poor histology inevitable when immunofluorescence is performed on frozen tissue sections. An immunoperoxidase study therefore was undertaken of the ductal pancreatic carcinomas induced in female LGV Syrian hamsters by N-nitroso-bis(2-oxopropyl)amine [(BOP) CAS: 60599-38-4]. Artifactual clotting and fibrinolysis associated with tumor removal were avoided by systemic anticoagulation and antifibrinolysis. Fibronectin and residual fib were prominent components of tumor stroma. Prominent fib deposits also were found in a new location: the basement membrane zones of atypical pancreatic ducts and invasive carcinomas. In contrast, fib deposits were never found in the basement membranes of blood vessels, nerves, or pancreatic acini of BOP-treated or normal animals, or in the ductal basement membranes in the normal pancreas. Ducts with marked atypicality and invasive pancreatic carcinomas frequently exhibited discontinuous basement membrane staining for fib, which often paralleled loss of staining for the integral basement membrane proteins--type IV collagen and laminin. Loss of acquired fib basement membrane staining with malignant disease progression may serve as a new marker for local tumor invasion.

Adenocarcinoma↗

Vanadate supplements and 1,2-dimethylhydrazine induced colon cancer in mice: increased thymidine incorporation without enhanced carcinogenesis.

Because vanadate ion is a potent mitogen and accumulates in the gut of rodents fed vanadate supplements, effects of ammonium metavanadate in drinking water (10 ppm or 20 ppm) were studied on the development of large bowel neoplasms in mice treated with 1,2-dimethylhydrazine (DMH) (20 mg kg-1 weekly for 20 weeks). In the colon at 30 weeks DMH treatment caused a 14% increase in RNA content, an 18% increase in DNA content, and 33% deeper crypts. Vanadate at either 10 ppm or 20 ppm decreased RNA content by approximately 11%. Although vanadate increased thymidine incorporation 210% to 550% compared with controls, it had no influence on the attack rate, incidence, or histological type of tumours induced by DMH.

1,2-Dimethylhydrazine↗

High ornithine decarboxylase activity and polyamine levels in human colorectal neoplasia.

Polyamines are required for cell proliferation, and ornithine decarboxylase (ODC) is the first and probably rate-limiting enzyme in their synthesis. Tissue containing colonic or rectal adenocarcinomas (N = 34) or polyps (N = 6) and noninvolved paired colonic mucosa were obtained from fresh surgical specimens. ODC activity was elevated (mean: 320%) in both the cancer and polyps. In noninvolved colonic mucosa of tumor-bearing specimens, ODC activity was 165% that of colonic mucosa of non-neoplastic disease. Concentrations of polyamines in neoplasms were 121-214% increased, as compared with normal mucosa; those of spermidine and spermine varied inversely with the histological grade of the tumor. High levels of ODC activity and of polyamines were features of neoplasia, but not of malignancy alone. These characteristics of colonic neoplasia suggest its susceptibility to control by inhibition of ODC.

Adenocarcinoma↗

Biliary stricture dilatation: multicenter review of clinical management in 73 patients.

Eighty-nine biliary strictures in 73 patients who had undergone percutaneous balloon dilatation were reviewed to determine long-term patency rates and clinical management problems. The majority of dilatations were performed in patients with anastomotic strictures (n = 44), iatrogenic strictures (n = 28), and strictures associated with sclerosing cholangitis (n = 17). Patency rates after 36 months or more were 67%, 76%, and 42%, respectively. Complications, mostly minor, occurred in less than 7% of patients. Of patients with significant biliary obstruction, 15% had little or no intrahepatic biliary duct dilatation demonstrated by cross-sectional imaging and/or direct cholangiography. No definite conclusions could be drawn about the utility of long-term internal/external stenting.

Bile Duct Diseases↗

Prognosis of clinical stage I melanoma patients with positive elective regional node dissection.

We tested 12 clinical and histologic variables to see which ones best predicted death from melanoma in 66 patients with positive elective regional node dissections (clinical stage I, pathologic stage II [CSI, PSII]). Despite the presence of lymph node metastases, not all patients had poor prognoses. Patients with tumors less than or equal to 3.5 mm and a percentage of positive nodes less than or equal to 20% had a 7-year survival rate of 66%. Within this low-risk group the subset with primary lesions on the trunk or extremities (except hands and feet) had a 7-year survival rate of 76%. This compares with poor 7-year survivals of 29% and 30% observed in other defined high-risk groups. Our results confirm and extend earlier observations concerning the prognoses of CSI, PSII melanoma patients and are relevant to any ongoing and future studies concerning elective regional node dissection (ERND) or adjuvant therapy trials in melanoma.

Actuarial Analysis↗

Inhibition of ileal and colonic ornithine decarboxylase activity by alpha-difluoromethylornithine in rats: transient atrophic changes and loss of postresectional adaptive growth.

To determine the role of putrescine synthesis in adaptive hyperplasia of the ileum and colon, DL-alpha-difluoromethylornithine (DFMO), an enzyme-activated, irreversible inhibitor of ornithine decarboxylase (ODC), the enzyme controlling putrescine biosynthesis, was fed to rats after excision of the proximal half of the small bowel. A rise in ODC activity (280% in the proximal ileum, 62% in the proximal colon) and a rise in putrescine content (220% in the proximal ileum, 250% in the proximal colon) normally accompanied characteristic cytochemical adaptive increases in the ileum and colon at day 6. Inclusion of 1% DFMO (2.1 gm/kg/day) in drinking water for 12 hours before operation and for 14 days thereafter decreased ODC activity by 85% to 96%, reduced levels of putrescine and spermidine and measurements of the adaptive response by 50% in the ileum, and abolished the adaptive response in the colon. During the first 10 days of DFMO feeding, villous atrophy and other hypoplastic changes occurred in control rats, but by 14 days of DFMO feeding atrophy and hypoplasia were no longer present. Although DFMO inhibits adaptive hyperplasia occurring in the ileum and colon of rats after resection of the proximal half of the small bowel, spontaneous recovery of villous atrophy occurs during further DFMO feeding and may protect the host during chemotherapy.

Adaptation, Physiological↗

Pancreatic cancer in the Syrian hamster induced by N-nitrosobis(2-oxopropyl)-amine: cocarcinogenic effect of epidermal growth factor.

Because epidermal growth factor (EGF) is rapidly bound and internalized into rat pancreas, stimulates uptake of tritiated thymidine, and increases pancreatic weight, a cocarcinogenic effect on pancreatic cancer seemed likely. Pancreatic adenocarcinomas were induced in 70 female Syrian hamsters by 19 weekly s.c. injections of N-nitrosobis(2-oxopropyl)amine (BOP) (10 mg/kg). From Wk 5 through Wk 8 of BOP injections, additional s.c. injections of EGF (5 micrograms every 3 days for 10 injections) were given to 45 animals, while 25 received saline solution. An additional group of 10 received EGF alone, and another 10 animals received saline solution alone (controls). Eleven wk later, the mean body weight of EGF-treated animals increased by 29% as compared with that of controls, and their mean pancreatic weight relative to body weight increased by 44% as compared with controls. The mean body weight of EGF + BOP-treated animals increased by 10%, and their pancreatic weight relative to body weight increased by 22% as compared with that of animals treated with BOP alone. The incidence of pancreatic cancer in the EGF + BOP-treated animals was 75% versus 44% in those treated with BOP alone (P = 0.016). No tumors developed in either animals treated with EGF alone or control animals. EGF augments pancreatic carcinogenesis induced by BOP. The incidence of bronchial carcinomas doubles.

Adenocarcinoma↗

Augmentation of 1,2-dimethylhydrazine-induced colon cancer by experimental colitis in mice: role of dietary vitamin E.

Because ulcerative colitis predisposes to colonic cancer, for determination of the effect of colitis on experimental colon carcinogenesis, rectal instillations of peptides that attract and activate neutrophils were used to induce colitis in CD-1 (ICR) BR mice receiving 20 weekly injections of the carcinogen 1,2-dimethylhydrazine [(DMH) CAS: 540-73-8]. From week 4 through week 15 of DMH injections, twice-weekly enemas of formyl-norleucyl-leucyl-phenylalanine were given to DMH-treated mice. The effect of the antioxidant vitamin E in the diet (1,750 IU/kg diet) was studied in another group of mice treated with DMH and having colitis. Four weeks after DMH was discontinued, cancer occurred in 9 of 28 (32%) animals with DMH plus control enemas, in 22 of 29 (76%) animals with DMH plus colitis (P = .001), and in 16 of 28 (57%) animals with DMH plus colitis plus supplemental vitamin E (P = .11 compared with the group with DMH and colitis). Colitis enhances DMH-induced colonic carcinogenesis.

1,2-Dimethylhydrazine↗

Jejunal mucosal DNA content and maturation. Inverse relation to serum gastrin levels in suckling and weanling rats.

Although pentagastrin has a tropic action on intestinal mucosa in suckling rat pups, and at weaning a rise in gastrin levels coincides with maturation of the intestinal mucosa, direct correlations of serum gastrin levels and intestinal maturation have yet to be made. Ten-day-old rats were subjected either to antrectomy to produce a 43% decrease in serum gastrin levels or to fundectomy to produce a 319% increase over gastrin levels in rumenectomized or normal animals. These changes were not associated with tropic or adaptive changes in jejunal or colonic mucosa as determined by jejunal and colonic DNA content, jejunal sucrase activity, jejunal villous height, or crypt depths in jejunum and colon at the beginning (day 15), middle (day 21), or end (day 27) of the weaning period. To the contrary, an inverse relation was found between serum gastrin levels and both jejunal mucosal DNA content and sucrase activity as an index of maturation.

Animals↗