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Neuroprotective therapy for Parkinson's disease (PD) is a treatment intended to prevent or reduce neuronal degeneration. Since clinical studies to evaluate such an effect would be prolonged, the choice of agents for use as possible neuroprotective therapy is based on the results of in vitro and animal experiments. Free radicals are currently regarded as the most important factor in the progression of PD. One current possible neuroprotective therapy is reduction of levodopa dose, since levodopa is a source of free radical formation. Dopamine (DA) metabolism inhibition, and administration of the DA agonist bromocriptine that eliminates hydroxyl free radicals have neuroprotective effects experimentally. The other candidates for neuroprotective agents are still under development. However, those whose clinical use is permitted should be considered for use, since patients with long-standing PD cannot wait until the neuroprotective efficacy of these agents is confirmed by clinical study.

The effects of acute exposure to cigarette smoke and systemic administration of nicotine on intestinal propulsion were investigated in rats. The propulsive activity was measured as migration of charcoal powder in the intestine. This activity was suppressed by acute exposure (10 min) to cigarette smoke and by nicotine (0.5 mg/kg x 2, s.c.) administration. This intestinal suppression was more marked in the rats given nicotine than in those exposed to cigarette smoke, whereas the plasma concentrations of nicotine in both rats were similar. These results suggest that acute exposure to cigarette smoke and nicotine administration delay gastric emptying and/or suppress intestinal propulsion, and that some components other than nicotine contained in cigarette smoke may attenuate the suppression of intestinal propulsion induced by nicotine.

Although a strong association has been established between chronic Helicobacter pylori infection and peptic ulcers, the role of H. pylori is not necessarily causative because there are many patients infected with H. pylori who do not develop peptic ulcer. Therefore, we studied the relationship between the gastric mucosal environment and the development of peptic ulcers. We examined 165 endoscopic biopsy specimens from the gastric mucosa of 33 patients with peptic ulcers using the 5-point gastric biopsy method. The follow-up biopsies done within 3 weeks were well correlated with the first biopsy samples. We also reviewed the clinicohistopathological findings of 2250 endoscopic biopsy specimens from 450 patients with active gastric and/or duodenal ulcers. Over 90% of the patients with duodenal ulcer, with or without gastric ulcer, had no fundic gland atrophy, and a high incidence of intestinal metaplasia and pyloric mucosal atrophy was found in the patients with gastric ulcer. These findings suggest that patients with concomitant active gastric and duodenal ulcers exhibit severe atrophic changes in the antral mucosa but not in the fundic mucosa.

We recently reported that stimulation of the arginine vasopressin (AVP) V1-receptor enhanced the pressor response in spontaneously hypertensive rats (SHR). In the present study, we investigated acute changes in systolic blood pressure (SBP) and heart rate (HR) after intravenous injections of AVP, OPC-21268 (a V1-receptor antagonist), and OPC-31260 (a V2-receptor antagonist), in anesthetized DOCA-salt hypertensive rats (DOCA) and age-matched sham-operated Wistar rats (control) to determine whether the pressor effect is specific to SHR or is present in other hypertensive animal models. SBP increased significantly in DOCA rats 9 min after injection of AVP 5 ng/kg without a concomitant increase in HR. Neither OPC-21268 3mg/kg nor OPC-31260 3mg/kg caused significant changes in SBP or HR. SBP tended to increase when AVP was administered after injection of OPC-31260. HR increased significantly 15 min after the combined treatment with OPC-31260 and AVP in DOCA rats compared with control rats. SBP did not change significantly when AVP was administered after injection of OPC-21268 in DOCA or control rats, but HR decreased significantly from 1 to 4 min after injection of AVP in DOCA rats. Our results suggest that V1-receptor stimulation does not enhance the pressor response in the DOCA rat, which is a model of volume-dependent hypertension, suggesting that the AVP system, especially V1-receptor, is not as important in the development or maintenance of hypertension in DOCA rats as in SHR.

The results of rotationplasty for patients with osteosarcoma around the knee joint are presented. After an average observation period of 13.3 months, there has been no local recurrence or metastasis. The ankle joints (the new knee joints) of the patients were able to support their body weight with an average range of motion of 75 degrees. All patients could walk well without crutches and without risk of the giving way phenomenon. The average rate of the functional evaluation according to the re-modified system by Enneking was 84.5% (range, 80.0-86.7%). No patient had psychological trouble in accepting the shortened and rotated extremity. The results show that rotationplasty is a useful reconstructive method for the treatment of osteosarcoma around the knee joint.

It has previously been confirmed that the guinea pig has aggregations of 10-20 lymphoid follicles at the junction of the nasal cavity and the nasopharyngeal duct. The vascular architecture of this nasal-associated lymphoid tissue (NALT) was studied by the corrosion cast/scanning electron microscope method. The NALT was supplied by branches of the inferior nasal artery. These afferent arterial branches gave off arterioles to the follicles and the interfollicular regions, where the arterioles ramified into capillaries. Some of these arterioles reached the subepithelial region to form a single-layer dense capillary network. The subepithelial capillaries gathered into short collecting venules, which in turn drained into high endothelial venules (HEV) in the interfollicular region. The HEV, which also receives tributaries from the follicular and interfollicular capillary plexuses, descended in the interfollicular regions and finally flowed into the efferent veins at the bottom of the NALT. Indentations impressed by high endothelial cells (HEC) were prominent on the surface of the HEV casts, and their frequency was larger in the upper course or segments than in the lower. This suggests that the incidence of HEC in the upper segments is higher than in the lower segments, and these findings are consistent with the hypothesis that some substances which are taken up into the subepithelial capillaries and transported to the venules induce differentiation and maintain of HEVs.

Three patients with severe halothane-induced liver injury are described. All patients received halothane anesthesia twice within a short period. High fever and jaundice were noticed soon after the second operation. The prothrombin time was less than 40%, and eosinophilia was greater than 7% prior to these symptoms. Other causes of liver injury were excluded. Diagnostic criteria for halothane-induced liver injury are proposed.

The effect of coenzyme Q10 (Co Q10) was examined on the survival time and lipid peroxidation of adriamycin (ADM)-treated ICR mice. Co Q10 showed a protective effect against a subacute toxicity in mice induced by two intraperitoneal administrations of ADM (15 mg/kg). The group treated orally with 10 mg/kg of Co Q10 showed the longest survival time of all the groups studied (16.81 +/- 10.29 days, mean +/- S.D.) and a significantly longer survival time (p less than 0.001) than the ADM-alone group (7.48 +/- 1.99 days). The inhibitory effect of Co Q10 on the plasma and tissue lipid peroxidation levels did not correlate with the effect of prolonging the survival time of mice. Co Q10 tended to inhibit rises in plasma and liver lipid peroxidation levels induced by ADM administration, but there was no statistically significant difference between treatments. There was a statistically significant different inhibitory effect in the kidney lipid peroxidation levels, but was not in those of the heart.

Childhood leukemia, especially acute lymphocytic leukemia, can now be completely cured by a multimodality approach in one out of every two patients. Since prolonged maintenance therapy with anti-cancer agents for three years is required for complete cure, a significant problem during this course of treatment is death due to secondary infection. Those with childhood leukemia receiving anti-cancer chemotherapy who became secondarily injected with chicken pox can now be treated successfully with interferon in the four cases reported here. Chicken pox was cured even while one of them was in relapse. Therefore, it can be said that a bright prospect, namely interferon, is on the horizon in the treatment of secondary viral diseases associated with acute leukemia.

The whole body including extended processes of Ito's fat-storing cells was observed by scanning electron microscopy in rat liver injured with lithocholic acid (LCA). Necrotic foci developed in the midlobular zone 48 h after LCA administration. Demonstration of Ito cell bodies around the foci was probably facilitated by easy detachment of hepatocytes from Ito cells. The body and the processes were located mainly between the sinusoidal endothelium and hepatocytes; sometimes they were between hepatocytes. Ito cells often were proximate to collagen fiber bundles and sometimes were attached to them. The cell body was flatly round or elliptic, 7 to 12 micron in diameter. Its surface was finely undulated with microvillous projections about 0.1 micron in length. Branching patterns of the processes resembled a fern-leaf mantling the sinusoidal endothelium. The trunks of the processes were about 2 micron in diameter and 20-30 micron in length. These processes tapered, branching into thinner processes, with the most peripheral being 0.1 micron in diameter. Ito cells and their branching processes likely strengthen sinusoidal walls and control blood flow in the sinusoids.

The effect of cecectomy on food intake and defecation was studied in Wistar rats fed ad libitum or under restriction. Food intake, fecal output, dry matter and water content of feces, and numbers of scybala increased significantly in both groups of cecectomized rats. The weight of scybala and their dry matter and water content also increased after cecectomy. Water intake did not change significantly. It was considered that changes in the parameters after cecectomy may have resulted from lowered digestion and enhancement of propulsive activity in the gastrointestinal tract.

In guinea pigs whose pelvic nerves were bilaterally sectioned, afferent stimulation of rectoanal branches of the pelvic nerve (PAS) could produce an intense contraction in the rectum similar to propulsive contractions elicited during defecation. The mechanism of this reflex was analyzed. Rectal contraction by PAS was abolished after transecting the spinal cord at T13 or sectioning the lumbar splanchnic nerves (LSN) or lumbar colonic nerves (LCN), but was unaffected by severing the intermesenteric and hypogastric nerves. Rectal contraction induced by PAS was abolished peripherally by atropine, guanethidine or yohimbine, while propranolol had no affect. Yohimbine antagonized the inhibitory effect of LSN or LCN stimulation on atropine-sensitive rectal contractions. It may, therefore, be concluded that PAS blocks the inhibition, by LCN efferents acting through alpha-adrenoreceptors, of cholinergic neurons in the myenteric plexus, thus facilitating recto-rectal propulsive contractions initiated by the defecation reflex.

Experimental hepatocellular carcinoma (HCC) in rats did not take up intravenously administered indocyanine green (ICG) and trypan blue, while surrounding tissue did. The lack of ICG uptake was also observed by peritoneoscopy in patients with HCC. The contrast between ICG-stained cirrhotic nodules and HCC tumors was intensified with infrared photography. Non-uptake of dyes by HCC cells may enable discrimination between tumors and normal cells.

Rat Kupffer cells were observed and counted under a scanning electron microscope after a single dose of zymosan. The cell number increased after 24 h and reached 2 times the control after 72 h. The percentage of cells presenting numerous microvilli increased from 24% to 86% over the same period. Carbon clearance, a measure of phagocytic activity, decreased temporarily, regained control values after 12 h, and attained a 4-fold elevation at 72 h. Phagocytic activity paralleled Kupffer cell number, but increased more relatively. This result probably reflected activation of resident Kupffer cells as noted by numerous thick microvilli.

We report a case of a right buccal cavernous hemangioma with two phleboliths in a 23-year-old man. Consideration of the literature on the cases of hemangioma with phlebolithiasis in the maxillofacial and oral regions in Japan is given in this report.

Using C3H/He mice, the antitumor effect of lipopolysaccharide (LPS) alone and in combination with Lentinan extracted from Lentinus edodes was studied. The influence of LPS on cellular immunity and the antitumor effect of the tumor necrosis factor (TNF) were also examined. LPS, which was administered into mice with tumor, induced hemorrhagic necrosis of the tumor within 48 h, demonstrating a high antitumor effect. When LPS was used in combination with Lentinan, the tumor growth was significantly inhibited as compared to that in the control mice. The combination of LPS and Lentinan prevented a decrease in the delayed type hypersensitivity in tumor bearing mice. Application of rabbit serum containing TNF resulted in hemorrhagic necrosis of the tumor within 48 h, as with LPS.

A progesterone receptor (PR) in human uterine cervical nuclei was demonstrated by a nuclear exchange assay using a synthetic progestin, promegestone (R5020) as a radio-labeled ligand. Total exchange of previously bound progesterone with R5020 was achieved by incubation at 0 degree C for 3 h. A 0.6 M KCl solution was used to extract the nuclear PR in uterine cervical tissue, and the dextran coated charcoal (DCC) method was used to separate the free [3H] R5020 from the bound form. Scatchard plots of nuclear PR binding showed two components with dissociation constants of Kd = 2.3 X 10(-10) and 4.6 X 10(-9) M. Three histological regions of the uterine cervix was studied as to their nuclear PR contents throughout the menstrual cycle. In the follicular phase, the connective tissue (CT) had the highest PR concentration (658.9 fmole/mg DNA), followed by the columnar epithelium (CE) (253.6 fmole/mg DNA), and the squamous epithelium (SE) (184.7 fmole/mg DNA). In the luteal phase, there was no significant difference among the three regions. Comparing these phases of cycle revealed that the CT had higher PR contents in the follicular phase than in the luteal phase, but no such difference was found in the CE or SE. These three regions had the same Kd value in both phases.

An enzyme-linked immunosorbent assay (ELISA) for the purpose of detecting the albumin receptor on hepatitis B virus surface antigen (HBsAg) particles was developed. Patient sera with moderate to high receptor values demonstrated significant correlations with serum DNA-polymerase activity (p less than 0.005), but not with HBeAg titer. Within one year of the study of 47 HBeAg-positive patients, only in the group of 12 patients with the moderately high values and 9 with low values, did 2 (16.7%) and 6 cases (66.7%) sero-convert, respectively. These results suggest that the albumin receptor might be a useful marker of HBsAg-positive patients.

The dispase perfusion technique was used to isolate liver cells from adult rats. The optimum conditions for obtaining many isolated liver cells with high viability were an enzyme concentration of 2000 U/ml, a pH of 7.5 and a perfusion time of 20 min. The population of isolated liver cells prepared with dispase consisted of 43.6% cells with diameters less than 20 micron and 56.4% cells with diameters above 20 micron. The isolated liver cells were cultured in basal culture medium either supplemented with or without dexamethasone (1 X 10(-5)M) and insulin (10 micrograms/ml). The addition of hormones to the culture medium improved the attachment efficiency of the isolated liver cells and delayed the disappearance of mature hepatocytes. Epithelial-like clear cells proliferated early in primary culture even in the presence of hormones. Therefore, functioning mature hepatocytes and proliferating epithelial-like clear cells coexisted well in the hormone-containing medium. Furthermore, the number of cultured cells reached a maximal level earlier in the presence of hormones than in the absence of hormones. The level of TAT activity in primary cultured cells was higher up to 3 days after inoculation in the presence of hormones than in their absence. No difference between G6Pase activity in primary cultured cells in the presence of hormones and that in the absence of hormones was found.

Anti-IgE-induced histamine release from basophils was examined in 46 asthmatic subjects using a whole blood method. Basophils from subjects less than 30 years old released more histamine than those from subjects aged 41 to 50. The age at onset of the disease also affected the reactivity of basophils to anti-IgE: basophils showed a high response in subjects whose age at onset was between 0 and 10 years, and low response in the subjects whose age at onset was between 41 and 50 years. There was a correlation between histamine release and serum IgE levels. However, individual dose-response curves of histamine release varied greatly in whom serum IgE levels were low.