Insulin receptor regulation in minimal deviation hepatoma cell line.

Treatment of H4 hepatoma cells with the lectin wheat germ agglutinin (WGA) in the concentration range of 10-25 micrograms/ml increased 125I-insulin binding fivefold as compared to control binding in untreated cells. The increased insulin binding was rapid, readily reversible, and correlated with a 10-fold increase in the binding affinity of the receptor for insulin. Kinetic studies indicate that this increased affinity resulted from a decrease in the dissociation rate. The effect was specifically mediated by the lectin since it was reversed by simultaneous incubation with the monosaccharide N-acetyl-D-glucosamine (50 mM) or the disaccharide N,N'-diacetylchitobiose (1 mM). The WGA-mediated increase in insulin binding was not caused by inhibited insulin degradation. While WGA (5 micrograms/ml) mimicked insulin to induce stimulated uptake of [3H]aminoisobutyrate, the lectin failed to enhance the biological sensitivity of H4 hepatoma cells to insulin. At higher concentrations of WGA (125 micrograms/ml), interference with the insulin-mediated response was observed. Trypsin treatment of H4 hepatoma cells prior to measuring binding of 125I-insulin in the presence of increasing concentrations of native insulin, led to a leftward shift of the competition curve, indicating an increased affinity of the receptor. No further increase was observed when the trypsin-treated cells were subsequently exposed to WGA. These results suggest that trypsin treatment and WGA exposure may increase the affinity of the receptor by a similar mechanism. The results are consistent with the concept that WGA and trypsin decrease interaction between insulin binding and receptor affinity regulating components in the plasma membrane, leading to an increase in the affinity of the receptor for insulin.

Fluoride therapy in metabolic bone disease.

Multiple forms of treatment are used for osteoporosis, Paget's disease of the bone, and osteogenesis imperfecta. Because of the effect of fluoride (F) on bone, these bone conditions may benefit from F therapy. In the present study, the metabolic effects of two dose levels of F (20 and 45 mg, given as sodium fluoride) were studied on calcium (Ca) and F metabolism in patients with osteoporosis, whereas the effect of the 45-mg dose was studied in patients with Paget's disease. In patients with osteoporosis, the retention of F increased with increasing F intake, indicating F deposition in bone. However, only the 45-mg dose decreased urinary Ca excretion. F did not decrease fecal Ca excretion, indicating that the intestinal absorption of Ca did not improve during F therapy. This was confirmed in 47Ca absorption studies. The duration of F therapy was 3 months, utilizing the 45-mg dose. Clinically, the patients experienced relief of bone pain, and the onset of this change coincided with the decrease in urinary Ca. The 3-month course of treatment was sufficient for alleviation of clinical symptoms for many months and even years. In patients with Paget's disease, F supplements decreased urinary Ca and also resulted in relief of bone pain. F therapy for osteogenesis imperfecta resulted in decreased fracture incidence.

Women alcoholics: prevalence estimates and their problems reflected in turn-of-the-century institutional data.

Prevalence estimates of women alcoholics first appeared in the late nineteenth century; and between 1884 and 1912, data on some 24,200 institutionalized alcoholics produced male-female patient ratios ranging from 3:1 to 9:1. These estimates, however, suffered from some of the same difficulties inherent in modern prevalence figures: "Hidden alcoholism" and a lack of treatment facilities caused the data to under-report women, while patient sex ratios varied by socioeconomic status. These data problems are largely unresolved, and securing reliable prevalence information on women alcoholics remains a frustrating matter for both the social historian and the modern alcohol researcher.

Studies of fluoride metabolism in man. A review and report of original data.

The dietary intake of fluoride and the fluoride excretions in urine and stool were determined under controlled conditions in man. Fluoride balance studies have shown that the urinary fluoride corresponds to 50--60% of the intake, the fecal fluoride was very low, corresponding to 6% of the intake, and approximately 1 mg fluoride was retained per day during an average fluoride intake of 4.3 mg/day. The fluoride intake depended on the amount of fluoridated water consumed. The dietary fluoride content ranged from 1.2 to 1.5 mg/day. During the intake of supplemental fluoride the fluoride excretions increased but the ratio of the urinary/fecal fluoride was similar. Added fluoride is well retained. Following its discontinuation, very small amounts of the retained fluoride are excreted for several days. Inorganic elements, such as calcium, phosphorus, and magnesium, which have been shown to decrease the intestinal absorption of fluoride in animals were ineffective in man, while aluminum, given as aluminum-containing antacids, markedly decreased the intestinal absorption of fluoride and thereby decreased the retention of fluoride.

Effect of calcium, phosphorus, magnesium, and aluminum on fluoride metabolism in man.

The studies of the interaction of fluoride with minerals in man have shown that: 1. in contrast to observations made in animals, the high intake of calcium, phosphorus, and magnesium in amounts that can be used in humans did not inhibit the intestinal absorption of fluoride in man; 2. the lack of effect of added calcium, given in divided doses, on the intestinal absorption of fluoride has relevance for the use of a high calcium intake during fluoride therapy for osteoporosis; 3. aluminum as the hydroxide, commonly used as an antacid in clinical medicine, significantly decreases the intestinal absorption of fluoride. This inhibitory effect, in conjunction with the known effects of aluminum-containing antacids in causing calcium loss as a consequence of phosphorus depletion, may contribute to the development of skeletal demineralization.

"Temperance tales". Antiliquor fiction and American attitudes toward alcoholics in the late 19th and early 20th centuries.

Much of the American temperance fiction and graphics (the "Temperance Tales") of the mid-1800s to the early 1900s demonstrated a relatively sophisticated understanding of the progressive nature of alcoholism. In explaining the alcoholic process to the public, this fiction contributed to the general belief that the typical alcoholic was a Skid Row-like derelict.

Characteristics of hospitalizations and death cases of diabetic patients in a general hospital.

Hospital admissions of diabetic patients were analyzed in relation to total hospital admissions, during a period of 7 years in a general hospital. The prevalence of hospitalization of diabetic patients was 2.5%. The female to male ratio was 1.4:1.0. Admissions of diabetic patients to hospital are mainly in the older age groups. By the age of 40 years, 73.4% of the total hospitalizations occur but only 13.0% of these hospital admissions are diabetics. The age at time of death of admissions ending fatally is similar in both the total and the diabetic admission groups to hospital. When the percentages of hospital admissions which terminated in death are calculated for age groups, an increase is specifically demonstrated in the diabetic group compared to the total admission group. Thus, diabetes is a complicating factor which increases mortality in people over 50 years of age.

Intestinal absorption of 47Ca in elderly patients with osteoporosis, Paget's disease and osteomalacia. Effects of calcitonin, oestrogen and vitamin D2.

The intestinal absorption of 47Ca was studied in elderly patients. A standard dose of 10 muCi of 47Ca was given orally. The radioactivity was measured in the plasma, and expressed as percentage of the administered dose per litre plasma. As a control group served 12 patients aged 60-80 years, hospitalized for observation for various reasons, receiving no medical treatment and not suffering from any known metabolic bone diseases or other metabolic pathological conditions. Results of kinetic curves demonstrate in elderly patients a decreased absorption with maximum specific activity in plasma reached at 120 min, when compared to data from the literature referring to a group of young people with a mean age of 35 years. Oestrogen treatment, given as ethinyl oestradiol 10 mug once daily per os for 10 days proved to increase 47Ca absorption as was demonstrated in 2 patients with osteoporosis. The effect of calcitonin (160 MRC units given 45 min before the test) on calcium absorption, in 5 patients with Paget's disease or osteoporosis appears as biphasic: in the first hour depressing calcium absorption and then in the second and third hours increasing the absorption, suggesting a hyperparathyroid state secondary to the calcitonin effect. The vitamin D2 treatment proved to increase calcium absorption.

[Gastrointestinal amyloidosis]. / Amylose gastro-intestinale

A series of 29 cases of amyloidosis of the alimentary tract is reported. Five cases (17%) were primary amyloidosis; 14 cases (48%) were amyloidosis secondary to other diseases (such as chronic inflammatory and neoplastic diseases); 10 cases (35%) were amyloidosis of the heredo-familial type connected with Familial Mediterranean Fever. In 23 patients (79%) the diagnosis was established by biopsies, and in 6 more cases on autopsy. Gastrointestinal involvement was found in all age groups. Gastro-enterologic complications observed in the present series include: diarrhea, malabsorption, ileus and gastrointestinal bleeding. In addition other conditions such as jaundice (3 cases), esophagitis and acute hemorrhagic pancreatitis were observed. In 22 patients proteinuria was observed and in 13 patients the nephrotic syndrome. Among 17 patients, in 11 the clinical picture before death was that of terminal renal failure. The survival after diagnosis among 14 patients reached 4 years in 9 cases, and 19 years in one case. The diagnostic value of the rectal biopsy is emphasized.