Endocrine Effects of Maternal Alcoholization: Plasma and Brain Testosterone, Dihydrotestosterone, Estradiol, and Corticosterone

Maternal ethanol consumption was associated with reduced levels of dihydrotestosterone in the brains of 1–2-day-old male rats when compared to those of sex-matched pups obtained from dames that were fed sucrose. In contrast, brain levels of corticosterone were increased significantly in the pups of ethanol-fed animals when compared to those from sucrose-fed controls. Brain and plasma estradiol did not differ between groups. These results suggest that maternal ethanol consumption may influence the central nervous system and plasma levels6000 of certain steroidal hormones in the offspring.     

Reactive hyperplasia of paracortex and germinal centers of the regional lymph nodes in gastric carcinoma cases as a favorable prognostic indicator

The prognosis of 141 patients subjected to curative resection for gastric carcinoma was analyzed with special reference to the paracortex, germinal centers and sinus histiocytes in the regional lymph nodes. Five year survival rates of the patients with paracortical and/or germinal center hyperplasia (PH and/or GH) was definitely superior to those without such hyperplasia. This difference was most pronouced in those with moderately advanced stage. The incidence of lymph node metastasis was lower in the patients with PH or GH. The presence of sinus histiocytosis (SH) seemed to be correlated neither with a longer survival nor with lower incidence of lymph node metastasis. No close correlation was found between Ph, GH and SH on one hand and histological types of the primary gastric carcinomas on the other. These results suggest that cell mediated and/or humoral immune response may play an important role in host resistance against gastric carcinoma.     

Studies on mechanisms of diarrhea induced by fusarenon-X,a trichothecene mycotoxin from Fusarium species

Cardinal signs of red mold toxicosis in man and farm animals are vomiting, nausea, diarrhea, and food refusal. The red mold toxicosis has been suggested to be induced by trichothecenes which are produced by Fusarium fungi. Fusarenon-X (F-X) is one of the trichothecene mycotoxins. The ip injection of F-X to rats caused watery diarrhea 36 to 60 hr after injection. Autopsy done 24 hr after an injection of F-X revealed an expansion of the small intestine but no macroscopic bleeding into the lumen of the intestine. F-X increased the absorption rate of d-xylose from the intestine in vitro, caused leakage of intravenously injected Evan's blue dye into the intestinal lumen, and decreased the serum sodium level. However, F-X did not increase leakage of erythrocytes into the intestinal lumen. In histological observations, F-X shortened intestinal villi and caused an infiltration of erythrocytes into the intestinal lamina propria. These findings suggest that F-X may increase the permeability of the blood vessel wall and intestinal mucosal epithelium and thereby cause leakage of plasma contents into the intestinal lumen which eventually leads to diarrhea.     

Effects of CDP-choline on neurologic deficits and cerebral glucose metabolism in a rat model of cerebral ischemia

The effects of cytidine 5'-diphosphocholine (CDP-choline) on neurologic deficits and cerebral glucose metabolism were studied in a rat model of transient cerebral ischemia. Cerebral ischemia was induced by occluding both common carotid arteries for 20 or 30 minutes 24 hours after the vertebral arteries were permanently occluded by electrocautery. CDP-choline was administered intraperitoneally twice daily for 4 days after reestablishing carotid blood flow. CDP-choline at two dosages (50 and 250 mg/kg) shortened the time required for recovery of spontaneous motor activity in a dose-related manner; recovery time was measured early after reperfusion. Neurologic signs were observed for 10 days. High-dose CDP-choline improved neurologic signs in the rats within 20-30 minutes of ischemia. When cerebral glucose metabolism was assessed on Day 4, increases in the levels of glucose and pyruvate were accompanied by decreases in the synthesis of labeled acetylcholine from uniformly labeled [14C]glucose measured in the cerebral cortex of rats with 30 minutes of ischemia. High-dose CDP-choline also attenuated changes in these variables. CDP-[1,2-14C]choline injected intravenously 10 minutes after reperfusion was used for membrane lipid biosynthesis. These results indicate that CDP-choline has beneficial effects on brain dysfunction induced by cerebral ischemia, which may be due in part to the restorative effects of CDP-choline on disturbed cerebral glucose metabolism, probably by stimulating phospholipid biosynthesis.     

Assignment of gene coding human T-cell differentiation antigen,Tpl20, to chromosome 11

A pan T-cell antigen with a molecular weight of 120 kilodaltons (kd) is recognized by a monoclonal antibody, Tp120, produced in our laboratories. Two hybrid clones reactive with this Tp120 antibody were established from the fusion between concanavalin A-stimulated human peripheral blood lymphocytes and hypoxanthine-guanine phosphoribosyltransferase-deficient mouse T cell leukemia, BW5147. These two clones were also positive with two other antibodies, 12.1 and T12, both of which detect 120kd pan T-cell antigen. Karyotype analysis showed that one clone retained human chromosomes 6, 7pq^–, and 11, and the other maintained chromosomes 11 and 21. As soon as both of these clones lost the chromosome 11, the expression of Tp120 became negative. The presence of human chromosome 11 was confirmed by the isozyme analysis of lactate dehydrogenase-A. The results indicated that the presence of chromosome 11 was essential for expression of 120kd pan T-cell antigen.     

Pharmacokinetic animal PET study of FK506 as a potent neuroprotective agent.

The immunosuppressive agent FK506 (tacrolimus) has neuroprotective properties not only in rodents but also in nonhuman primates. To improve the accuracy of clinical studies of acute stroke, clinical dose setting based on brain concentrations of agents in humans is very helpful. We have already established a rapid-synthesis method for (11)C-labeled FK506; therefore, in the present study, we aimed to establish a method to measure brain concentrations of FK506 using (11)C-FK506 PET in monkeys. METHODS: Studies were performed on 3 male cynomolgus monkeys (Macaca fascicularis). FK506 (0.1 mg/kg) containing (11)C-FK506 was intravenously injected into the monkeys, and dynamic PET images were acquired for 30 min afterward. Arterial blood samples were collected 5 and 15 min after injection, and their radioactivities were measured by a gamma-counter. FK506 concentrations in brain and blood were calculated in units of moles per liter using the specific activity of the injected FK506. The PET study data were validated using an enzyme-linked immunosorbent assay. RESULTS: Seven minutes after administration, the radioactivity in the brain became constant and was maintained up to 30 min. We succeeded in measuring the FK506 concentration in the brain using (11)C-FK506 PET. Fifteen minutes after FK506 (0.1 mg/kg) administration, the concentrations in the cortex and striatum were 20.0 +/- 1.7 ng/g and 14.1 +/- 1.7 ng/g, respectively. FK506 concentrations in the blood correlated significantly with those measured by enzyme-linked immunosorbent assay. CONCLUSION: We successfully measured FK506 concentrations in anesthetized monkey brain and blood using (11)C-FK506 PET. These results indicate a potential method to measure FK506 concentrations in human brain. Additionally, a potential use for the PET technique in drug development has been demonstrated.     

Cardiovascular Responsiveness After Isotonic Exercise in Cirrhotic Patients: Study on Sympathoadrenergic and Renin-angiotensin Systems

Objectives: The aim of this study was to evaluate cardiovascular responsiveness after isotonic exercise in cirrhotic patients. Methods: Included were 11 cirrhotic patients and 10 age-matched normal suhjects, who served as controls. Hemodynamic data were obtained on each subject before and after muscle exercise on a treadmill (7 metabolic units). Plasma noradrenaline concentration and plasma renin activity also were determined. Results: In both groups, isotonic exercise increased heart rate and systolic arterial pressure, whereas diastolic arterial pressure was not modified. The increase in heart rate and systolic arterial pressure did not differ significantly between the two groups. Plasma noradrenaline concentration and plasma renin activity also were increased. The changes in plasma noradrenaline concentration and plasma renin activity was higher in cirrbotic patients than in controls ( P < 0.05, P < 0.05), although the differences were not significant when calculated as a percentage. Conclusions: Cardiovascular responsiveness to isotonic exercise is almost intact in cirrhotic patients. However, supernormal activation of the sympathoadrenergic and renin-angiotensin systems is required to maintain cardiovascular homeostasis in these patients.     

Neonatal subdural hematoma secondary to birth injury

In order to evaluate the treatment and prognosis of subdural hematoma in neonates, we analyzed 48 survivors in the 3-year period January 1979 to December 1981. Based on the CT findings, the hematomas were grouped into four types according to location: type I, localized around the posterior interhemispheral fissure (25 cases, 52%); type II, extending from the posterior interhemispheral fissure to the hemispheric convexity (5 cases, 10%); type III, extending from the incisura to the posterior fossa (15 cases, 31%); and type IV, subdural hematoma accompanied by intracerebral hemorrhage (3 cases, 7%). Intracranial pressure was measured via the anterior fontanel in 13 cases. In 10 cases of extensive hemorrhage, the pressure exceeded 200 mm H₂O. The age of the patients was from 0 to 7 days. There were 36 mature (75%) and 12 premature (25%) infants. The mothers were primiparous in 27 cases (56%). Fetal presentation was cephalic in 38 cases (79%), in 10 of which (21%) suction delivery was performed, and breech in 11. The fundus oculi was examined in 32 cases. Retinal hemorrhage was noted in 12 cases; it did not correlate with the type of hematoma or the intracranial pressure. Operations were performed in 13 cases; 1 of type I, 4 of type II, 5 of type III, and 3 of type IV. Functional prognoses were found to be as follows: type I, normal 15, abnormal 4, undetermined 6; type II, normal 4, abnormal 1; type III, normal 13, abnormal 1, undetermined 1; type IV, normal 1, abnormal 2 cases.