Compensatory renal hypertrophy in transplanted kidneys shows that the major regulators are humoral. Crosscirculation experiments are confirmatory indicating further that the regulators are short-lived and must be consistently present during the early phases of hypertrophy. Controls are difficult to achieve in other systems; variables relate to nutrition, means of assay, pharmacokinetics, and abnormalities produced by the experimental model itself. A simple hypothesis to account for the events precipitating renal hypertrophy might integrate the onsets of renal hyperemia soon after contralateral nephrectomy with the activation of pre-existing stimulators specific for the kidney.

Animals↗

PubMed1983

Adenocarcinoma and lymphoma of the small intestine. Distribution and etiologic associations.

Malignant small-bowel tumors in 171 patients over 64 years included 68 with adenocarcinomas, 41 with primary lymphomas, 50 with carcinoids, and 12 with sarcomas. The distribution of the carcinomas showed approximately 80% preponderance in the duodenum and proximal jejunum. A similar distribution in the upper small bowel in small-bowel carcinomas induced in Fischer and Sprague-Dawley rats by azoxymethane (90-160 mg/kg) suggests defense mechanisms within ileal mucosa. The clinical series from 1958 to 1976 included two Crohn's carcinomas (jejunum, defunctioned ileum), two jejunal cancers (lymphoma, carcinoma) associated with celiac disease, two duodenal carcinomas arising in villous adenomas, and one jejunal lymphoma following exposure to irradiation. Multiple primary malignancies were found in 20 to 25% of enteric cancers. Hemorrhage was more common with carcinoma than lymphoma, but lymphomas predominated considering perforation or a palpable mass. Both carcinoma and lymphoma had 75 to 80% resectability rates and 14 to 15% five-year postoperative survival rates. The prognosis was least poor for carcinoma of the jejunum, one third of patients with "curative" resections surviving five years.

Adenocarcinoma↗

PubMed1983

Growth and metabolic alterations after submandibular sialadenectomy in male mice.

Because the submandibular salivary glands of male mice are rich in growth factors such as epidermal growth factor and nerve growth factor, and because there are sporadic reports of sialadenectomized mice showing growth retardation and endocrine abnormalities, we studied oxidative metabolism and fertility after submandibular sialadenectomy. Despite similar intake of food, male mice (n = 60) deprived of submandibular saliva, either by duct ligation or gland excision, initially weighed 12-13% less than the sham controls and had a slower rate of growth (P less than 0.001). After 5 mo, mice with duct ligation caught up with the sham-operated mice, but the differences compared with submandibular-sialadenectomized mice were still apparent at 32 wk (P less than 0.001). The mean respiratory quotient of submandibular-sialadenectomized and duct-ligated mice was 0.71 instead of 0.88 as in the shams at 10, 20, and 30 wk after operation (P less than 0.01). No effect on fecundity was observed in either male or female mice following submandibular sialadenectomy.

Aging↗

PubMed1983

Hypersecretion of submandibular saliva in male mice: trophic response in small intestine.

The submandibular salivary gland of the male mouse and its secretions contain growth-promoting factors that accelerate cell proliferation in vitro and also have effects on the gastrointestinal tract in vivo. We therefore stimulated salivary secretion with isoproterenol for studies of the effects of submandibular saliva on intestinal cell proliferation; only submandibular glands respond to isoproterenol by releasing epidermal growth factors and other growth factors into the saliva. Submandibular sialadenectomized and sham sialadenectomized male mice on pair-feeding schedules were given isoproterenol intraperitoneally for 1 wk. A 44% increase in ribonucleic acid and a 13% increase in deoxyribonucleic acid were observed in the jejunum of animals with intact submandibular glands (p less than 0.001). In the ileum, there was a 26% increase in ribonucleic acid, a 47% increase in deoxyribonucleic acid, and a 28% increase in deoxyribonucleic acid specific activity (p less than 0.001). Morphometric measurements showed a 28% increase in villous height (p less than 0.001). No differences were found in colonic mucosa. Submandibular saliva increases the nucleic-acid content of mucosal cells and the villous height in the small intestine of male mice, presumably in part because of the growth factors it contains; a systemic metabolic change could also be present.

Animals↗

PubMed1983

Effects of alpha-difluoromethylornithine on the growth of experimental Wilms' tumor and renal adenocarcinoma.

Because polyamines are essential for cellular growth and differentiation, and because human renal carcinomas have spermidine levels that are higher than those in normal renal tissue, effects of 2-difluoromethylornithine (DFMO) on the growth of experimental renal tumors were investigated. DFMO is a specific enzyme-activated irreversible inhibitor of ornithine decarboxylase, the rate-limiting enzyme controlling polyamine biosynthesis. DFMO (2%) in drinking water was administered to BALB/c mice with intrarenal transplants of a renal adenocarcinoma cell suspension and to Wistar/Furth rats with s.c. transplants of a Wilms' tumor. At 28 days, renal carcinomas in DFMO-fed mice weighed 72% less than those in control animals (p less than 0.001). Wilms' tumor weight was not affected by DFMO feeding. DFMO caused 72 to 75% inactivation of ornithine decarboxylase activity and reduced putrescine levels in renal carcinoma and Wilms' tumor, reduced spermidine levels in Wilms' tumor, and apparently raised spermine levels in the latter as a consequence. DNA content was not affected by DFMO feeding. The mean number of lung metastases in DFMO-fed, renal carcinoma-bearing mice was 0.1 and in controls was 1.4 (p less than 0.001). DFMO feeding increased survival of mice bearing renal carcinomas by 3.0 +/- 0.8 (S.E.) days (p less than 0.05), i.e., from 30.5 +/- 0.8 days to 33.5 +/- 1.2 days. DFMO did not affect the growth of Wilms' tumor; however, in renal adenocarcinoma, it reduced growth, prevented lung metastases, and increased survival.

Adenocarcinoma↗

PubMed1983

Inhibition of ornithine decarboxylase with 2-difluoromethylornithine: reduced incidence of dimethylhydrazine-induced colon tumors in mice.

2-Difluoromethylornithine (DFMO) was administered to 1,2-dimethylhydrazine (DMH)-treated mice to reduce colonic polyamine levels and mucosal hyperplasia. Mice received 1% DFMO in drinking water throughout the experiment and were given injections of DMH (20 mg/kg) weekly for 28 weeks. DFMO inactivated 93% of colonic ornithine decarboxylase activity. Although DMH treatment did not induce colonic ornithine decarboxylase activity by Week 28, the putrescine content was increased 31% in DMH-treated mice (p less than 0.01). Concurrent treatment with DFMO depressed putrescine content (42 to 63%) and spermidine content (27 to 38%), but it increased spermine content (18 to 22%). At Week 28 of treatment with DMH alone, RNA content was increased 8.6% (p less than 0.01), DNA content 10% (p less than 0.01), DNA specific activity 24% (p less than 0.01), and crypt depth 20% (p less than 0.01), but not in mice receiving DMH and DFMO. At 28 weeks, 13 of 17 mice (76%) treated with DMH alone had histologically confirmed colon cancers; of mice treated with DMH and DFMO, two of 18 (11%) had colonic tumors. Throughout the experiment, 50 colon cancers developed in 16 DMH-treated mice (mean, 3.12 tumors/mouse); three mice treated with DMH and DFMO developed three colon cancers total (p less than 0.001). Reduction of colonic polyamine levels after DFMO treatment prevents proliferative changes induced by DMH and reduces the incidence of tumors.

1,2-Dimethylhydrazine↗

PubMed1983

Effects of alpha-difluoromethylornithine and 5-fluorouracil on the proliferation of a human colon adenocarcinoma cell line.

Because alpha-difluoromethylornithine (DFMO) reduces the incidence of experimental colon cancers, inhibits the growth of human lung cancer cells and human leukemia cells in culture, and in combination with methylglyoxal (bis)guanylhydrazone induces remission in children with leukemia, its effectiveness against a human colon adenocarcinoma cell line (Colo 205) was tested alone and in combination with 5-fluorouracil (5-FU). Both DFMO (2 X 10(-4) M) and 5-FU (10(-6) M) inhibited Colo 205 cell proliferation. Above 5 X 10(-4) M DFMO (p less than 0.001) and at 10(-4) M 5-FU (p less than 0.001), Colo 205 growth was completely inhibited. Although DFMO did not sensitize Colo 205 cells to a noninhibitory concentration of 5-FU, the effectiveness of inhibitory concentrations of 5-FU and DFMO in reducing Colo 205 cell growth was additive. DFMO (2 X 10(-4) M) caused 89 to 93% inhibition of ornithine decarboxylase activity (p less than 0.001) and reduced levels of putrescine (93%; p less than 0.01) and spermidine (57%; p less than 0.02). Growth rate and the intracellular putrescine and spermidine contents were restored by 10(-6) M putrescine. DFMO could be an effective chemotherapeutic agent against human colonic cancer because of its effects at such unusually low concentrations in vitro.

Adenocarcinoma↗

PubMed1982

Skin lesions suspected to be melanoma should be photographed. Gross morphological features of primary melanoma associated with metastases.

We reviewed photographs of 256 primary cutaneous melanomas to determine the gross morphological correlates of metastases. Seven and a half years after diagnosis, the melanomas with ulceration occupying at least 80% of their surface had the highest rate of metastases (85%), and melanomas without a nodule had the lowest metastatic rate (11%). Melanomas with nodules had a metastatic rate of 62%, and this rate increased in direct proportion to nodule diameter. Even after adjusting for nodule diameter and ulceration, melanomas with single nodules located completely within the confines of an associated plaque had half of the metastatic rate of melanomas with nodules located at the periphery (abutting normal skin). These data suggest that (1) carefully recorded gross pathological data can augment the microscopic pathological data in the determination of prognosis; (2) skin lesions suspected to be melanoma should be photographed; (3) the photograph, if followed by surgical removal of the lesion, should be attached to the pathology report in the patient's permanent medical record; (4) nodule diameter is better correlated with metastases than the total lesion diameter (as traditionally held); and (5) the cytologically malignant melanocytes that constitute the less-raised portion of most melanomas may not be biologically malignant, thus enlarging the precursor concept for malignant melanoma. The TNM staging system for malignant melanoma could be modified to incorporate these data.

Biopsy↗

PubMed1982

Mouse kidney nonpolysomal messenger ribonucleic acid: metabolism, coding function, and translational activity.

To elucidate the distribution and function of mRNA in mouse kidney cytoplasm, we compared mRNA isolated from polysomal (greater than 80S) and native postpolysomal (20--80S) ribonucleoproteins with respect to synthesis and lifetime, sequence content, and translational activity. The 20--25% of cytoplasmic mRNA recovered from postpolysomal ribonucleoprotein is similar to polysomal mRNA in size (20--22S), in apparent half-life (11--13 h), in major products of cell-free translation, and in nucleotide complexity (approximately 4 x 10(7) nucleotides). The labeling kinetics of polysomal and postpolysomal mRNA suggest these mRNA populations are in equilibrium. [3H]cDNAs transcribed from polysomal and from postpolysomal poly(A)-containing mRNAs react with template mRNA and with the heterologous mRNA at the same rate (Cot1/2 approximately 6.3 mol.s/L) and to the same extent (95%). Therefore, these mRNAs are equally diverse and homologous and occur at similar relative frequencies. Postpolysomal mRNA directs cell-free protein synthesis at only approximately 30% of the rate of polysomal mRNA and to only 30% of the extent of mRNA from polysomes. Postpolysomal mRNA is approximately 3-fold less sensitive than polysomal mRNA to inhibition of translation by m7GMP, suggesting postpolysomal mRNA contains a greater fraction of molecules deficient in 5'-terminal caps. Postpolysomal mRNA may derive from renal mRNAs that initiate translation inefficiently and thus accumulate as postpolysomal ribonucleoproteins.

Animals↗

PubMed1982

Narrower margins for clinical stage I malignant melanoma.

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Humans↗

PubMed1982

Percutaneous radiographically guided catheter drainage of abdominal abscesses.

We performed computed body tomography and ultrasound-guided percutaneous catheter drainage in 45 cases of abdominal abscess. Evacuation of the cavity was achieved in 40 cases (89%), eliminating the need for surgery in 34 patients. There were six recurrent abscesses, all due to fistulous communications or recurrent infected tumor. Major complications were a lacerated mesenteric vessel and a small-bowel fistula. Drainage catheters were removed an average of seven days after insertion. In many cases, guided percutaneous radiological drainage is an effective alternative to operative therapy, especially in severely ill patients.

Abdomen↗

PubMed1982

Nerve growth factor potentiates stress-induced gastric ulceration.

Increased salivary flow stimulated by intravenous isoproterenol (IPR) (6 mg/kg) doubled the incidence of gastric stress ulceration in normal male mice, but not after submandibular sialadenectomy. The submandibular salivary glands in these mice secrete large amounts of several growth factors, including epidermal growth factor (EGF) and nerve growth factor (NGF). Intragastric instillation of a quantity of high molecular weight NGF equimolar to that in IPR-stimulated saliva doubled the incidence of stress ulcers after submandibular sialadenectomy. This action of NGF in vivo is not mediated by its nerve growth promoting properties nor its plasminogen activating property.

Animals↗