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OKY-1581, a thromboxane A2 (TXA2) synthetase inhibitor, was administered to cats with normal and constricted basilar arteries. At a dose of 60mg/kg (i.v.), both normal and constricted vessels dilated, and the mean arterial blood pressure (MABP) fell from 55 to 75 mmHg. If MABP remained constant, vessel diameter did not change. Subarachnoid hemorrhage (SAH) was simulated by intracisternal injection of autologous arterial blood. Regional cerebral blood flow (rCBF) was assessed by the heat clearance and H2 clearance methods. The two methods presented similar response profiles. rCBF responses to intravenous OKY-1581 fell into 3 categories: A) no change in rCBF, B) decrease in rCBF related to MABP and C) increase in rCBF in the presence of hypotension. Types A and B were observed in 3 out of 10 control cats and 4 out of 14 SAH-induced cats, with Type C responses in the remainder. There was no significant difference between the groups. While the results do not support a major role for TXA2 in cerebral vasospasm pathogenesis, OKY-1581 may still be useful in the treatment of cerebral vasospasm, as it improves distal and deep circulation and inhibits platelet aggregation.

In vivo in mammalian cells, ultraviolet-induced unscheduled DNA synthesis was less sensitive to aphidicolin than was replicative DNA synthesis. Replicative DNA synthesis in HeLa, HEp-2, WI-38 VA-13 and CV-1 cells was inhibited more than 97% by aphidicolin at 10 micrograms/ml, whereas aphidicolin inhibition of DNA synthesis in ultraviolet-irradiated cells varied between 30% and 90% depending on cell types and assay conditions. Aphidicolin inhibition of unscheduled DNA synthesis (UDS) in HeLa cells increased gradually with increasing aphidicolin concentration and reached approximately 90% at 100 micrograms/ml aphidicolin. A significant fraction of UDS in ultraviolet-irradiated HEp-2 cells was resistant to aphidicolin even at 300 micrograms/ml. Considered along with related information reported previously, the present results suggest that both aphidicolin-sensitive and insensitive DNA polymerases, DNA polymerase alpha and a non-alpha DNA polymerase (possibly DNA polymerase beta), are involved in in situ UDS in these ultraviolet-irradiated cells. Comparison of staphylococcal nuclease sensitivity between DNAs repaired in the presence and in the absence of aphidicolin in HEp-2 cells suggested that the involvement of DNA polymerase alpha in UDS favored DNA synthesis in the intranucleosomal region.

Resistant ascites was studied in 34 patients with liver cirrhosis and ascites. The patients were initially divided into 3 groups on the basis of the weekly cumulative ascites retention curve: patients relieved of ascites within 3 weeks of admission, patients relieved between 4 and 12 weeks and patients with ascites persisting beyond 13 weeks. "Resistant ascites" was defined as "ascites persisting for more than 13 weeks after admission to the hospital". The patients were then reclassified into 3 groups : Group A being those patients relieved of ascites within 12 weeks, Group B being those with resistant ascites and group C being those who died within 12 weeks of admission. There were no differences in age and sex distribution, etiology of liver cirrhosis, past medical history or physical findings among the 3 groups. However, Group B had higher levels of serum creatinine and blood urea nitrogen than Group A on admission. Serum bilirubin was higher and serum albumin was lower in Group C than in Group B, which indicates that Group C had greater liver cell failure.

Leucine decarboxylation in rat brain was investigated during acute hepatic failure, induced by partial hepatectomy after carbon tetrachloride (CCl4) pretreatment of rats. These rats presented metabolic alkalosis, and had significantly higher levels of arterial blood and brain ammonia than control and CCl4-treated rats. Brain leucine decarboxylation was elevated in rats with hepatic failure. This alteration correlated with arterial blood ammonia concentrations, and probably with elevated brain ammonia levels, as brain ammonia levels were directly related to arterial blood ammonia.

A 77-year-old man with Parkinson's disease of long standing, under treatment with L-DOPA and benserazide, was administered DL-threo-3, 4-dihydroxyphenylserine (DL-threo-DOPS), a precursor of norepinephrine, for 10 days. With this administration the patient's freezing phenomenon was remarkably improved, and his dysarthria also showed improvement. When DL-threo-DOPS was suspended, the frozen gait returned on the third day to almost the former level, even though he continued to receive L-DOPA and benserazide. After administration of DL-threo-DOPS, the CSF level of 3-methoxy-4-hydroxyphenylglycol (MHPG), a major metabolite of norepinephrine, was 127.5% of the pretreatment level. These observations suggest that DL-threo-DOPS can pass through the blood-brain barrier and change to norepinephrine, and that DL-threo-DOPS may be beneficial in the treatment of the freezing phenomenon of Parkinson's disease.

A 31-year-old female with chronic myelogenous leukemia, who developed myeloblastic involvement of the central nervous system during acute myeloblastic transformation of the disease, was treated with methotrexate intrathecally. The therapy produced prompt clinical response and complete reversal of abnormal cerebrospinal fluid findings. However, the patient expired 10 months following the acute blastic crisis.

Plasma immunoreactive CRF measured by radioimmunoassay decreased rapidly after intravenous injection of synthetic ovine corticotropin releasing factor (CRF) and showed a bi-exponential decay curve in five macaca fuscatas. Half lives of plasma immunoreactive CRF were 5.8 +/- 1.4 (Mean +/- SEM) min for the fast component and 38.3 +/- 2.4 min for the slow component. A bolus injection of 5 micrograms/kg CRF significantly increased the plasma cortisol level. CRF at 5 micrograms/kg induced a delayed response of ACTH and cortisol. Arginine vasopressin (AVP) at 0.5 micrograms/kg induced a slight increase in plasma ACTH and cortisol, but AVP at 0.1 micrograms/kg evoked no significant increase. When 0.5 micrograms/kg CRF and 0.1 micrograms/kg AVP were administered simultaneously, significant ACTH and cortisol responses occurred. The results indicate that CRF and AVP act synergistically to stimulate ACTH secretion in vivo.

Seventy patients with cervical carcinoma who underwent radical hysterectomy and pelvic lymphadenectomy were evaluated to assess spread to the vagina. The overall vaginal invasion rate was 34.2% (24/70), with 36% (21/58) by squamous cell carcinoma, 25% (2/8) by adenocarcinoma and 25% (1/4) by adenosquamous carcinoma. A high vaginal invasion rate (45.7%) was noted in cases in which the cervical lesion was greater than 21 mm (p less than 0.05). Combined parametrial extention (45%) and combined lymph node metastasis (33.3%) were significantly higher in the vaginal invasion cases. The diagnostic accuracy of colposcopy and the Schiller test was 80% and 67% respectively. Histologically, the course of vaginal invasion by squamous cell carcinoma could be divided into : a) continuous invasion (16/21), b) incontinuous invasion via vessel permeation (3/21) and c) combined invasion (2/21). Both cases of vaginal invasion by adenocarcinoma were noted to spread by vessel permeation. Of the 7 cases of vessel permeation, colposcopic examination was positive in only one case. A high percentage of parametrial involvement and lymph node metastasis was noted in the vessel permeation type.

Carbon tetrachloride (CCl4)-induced hepatotoxicity was potentiated by pretreatment with beta-phenethyl alcohol, abundantly present in sake. The injury was determined by serum GPT levels and histological examination. Similar results were observed in ethanol- and phenobarbital-pretreated rats. Acetaminophen-induced hepatotoxicity was not accentuated by beta-phenethyl alcohol or ethanol pretreatment. The activities of liver microsomal enzymes, such as cytochrome P-450, cytochrome b5 reductase, aniline hydroxylase and aminopyrine demethylase, were not altered in beta-phenethyl alcohol-pretreated rats. Thus, CCl4-induced hepatotoxicity potentiation by beta-phenethyl alcohol administration is postulated to be due to a mechanism other than increased free radical generation.

The prevention of hepatic encephalopathy by the intravenous infusion of a branched chain amino acid (BCAA)-enriched solution was investigated in methionine and ammonium acetate-treated rats whose liver was already injured with carbon tetrachloride. A BCAA-enriched solution protected the rats from entering a coma. The brain BCAA contents became higher, and the brain methionine and tyrosine levels and the ratio of glutamine to glutamic acid in the brain diminished after administering the BCAA-enriched solution.

Ferrous chloride solution was injected unilaterally into the sensorimotor cortex of rats to induce a chronic epileptic focus. Accumulation of cyclic AMP elicited by depolarizing agents was determined in slices from different cortical areas of rats 30-60 days after the injection. In anterior cortical areas which include the sensorimotor cortex, the cyclic AMP accumulation elicited by ouabain or a high concentration of potassium ion was greater in electrographic spike activity on the dominant side than on the other. In posterior cortical areas, no difference in cyclic AMP accumulation was detected. The regional difference in the depolarization-elicited accumulation of cyclic AMP is discussed with regard to the process of epileptic focus.

L-Cysteine (5.0 mmol per kg of body weight) was intraperitoneally injected into rats fed a 25% casein or 5% casein diet. Concentrations of acidic and neutral amino acids in various tissues were determined 2 h later. In the rats fed the 25% casein diet there was a tendency for tissue amino acid and glutathione levels to be slightly lower than controls. In the 5% casein diet group, however, concentrations of tissue amino acids and glutathione generally increased after L-cysteine administration. S-(2-Hydroxy-2-carboxyethylthio)cysteine (HCETC,3-mercaptolactate-cysteine disulfide), though in trace amounts, was detected in kidney and blood plasma in the 5% casein diet group. Increases in cysteine-glutathione disulfide in liver, kidney and erythrocytes in the 5% casein diet group were considerable. These results indicate that L-cysteine was rapidly metabolized in the 25% casein diet group through the oxidative pathway, while in the 5% casein diet group, in which liver cysteine dioxygenase activity is supposed to be quite low, the oxidative metabolism of L-cysteine decreased and part of the L-cysteine was metabolized through the transaminative pathway. Administration of 15.0 mmol L-cysteine per kg of body weight to rats fed the 25% casein diet resulted in an increase in cysteine-glutathione disulfide in liver, kidney and erythrocytes, and the appearance of HCETC in blood plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

<p>Murine sarcoma virus, CS-Moloney substrain, was inoculated intracranially into 2 litters of newborn Syrian hamsters within 24 h of birth. Seven of 12 hamsters which survived more than 30 days developed brain tumors in the cerebral cortex 104 to 153 days, 139 days on the average, after the virus inoculation. The tumors consisted of spindle-shaped, round or polygonal astrocytes which showed a positive reaction for glial fibrillary acidic protein by the immunoperoxidase method.</p>

The influence of surgical stress on the local graft-versus-host reaction (GVHR) in F1 mice was studied. Skin incision 1 day prior to injection of parental spleen cells produced impairment of popliteal lymph node enlargement; however, this effect was not observed when GVHR was induced 3 and 5 days after operation. Strong GVHR suppressive activity of spleen cells was observed three hours after leg amputation before a decrease in thymus weight became evident. The GVHR suppressive activity declined by six hours later, but a second peak of 60% inhibition was observed after 24 h. This suppressive activity completely disappeared by treatment with anti-Thy 1.2 and complement. This shows that the GVHR is suppressed by surgical stress, and that this suppression is due to suppressor T lymphocytes.

Using the technique of somatic cell fusion, we produced monoclonal antibodies to collagenase-digested human glomerular basement membrane (GBM). Fourteen monoclonal antibodies which reacted with normal human kidney in indirect immunofluorescence (IIF) studies were produced. An analysis of the binding patterns indicated that the antigens recognized could be divided into six broad groups. Monoclonal antibody B3-H10 (Group 1) reacted with only GBM in a fine granular pattern. A5-B12 and B5-C2 (Group 2) reacted with GBM and peritubular capillary in a linear pattern. B2-A12 (Group 3) reacted with only epithelial cells. Al-C9 and A4-E2 (Group 4) showed a mesangial pattern in glomerulus and a lineal pattern in tubular basement membrane (TBM), Bowman's capsule and peritubular capillary. A1-E1, A1-E11, A2-E6, A3-B6, A4-F8 and B5-H2 (Group 5) recognized determinants common to GBM, TBM, Bowman's capsule and/or peritubular capillary. A3-F1 and B5-E10 (Group 6) reacted with TBM and Bowman's capsule. The staining pattern of B3-H10 (Group 1) was characteristic because it was not linear, but finely granular along the GBM. The staining pattern of B2-A12 (Group 3) was also characteristic because only epithelial cells were stained, and processes of epithelial cells were observed as fine fibrils. To the best of our knowledge, these two types of monoclonal antibodies have not been reported previously.

A single injection of ferric nitrilotriacetate (Fe3+-NTA) caused a transitory increase in plasma immunoreactive insulin (IRI) and plasma immunoreactive glucagon (IRG) in rats. They reached maximum levels at 2 days after injection and returned to the normal range at 10 days. At 2 days after Fe3+-NTA injection, blood glucose level was normal but the glucose tolerance test (GTT) was impaired. There was a further increase in plasma IRI level and IRG level was suppressed after glucose loading. At 10 days after Fe3+-NTA injection, glucose tolerance was normal and IRI also returned to the normal range. No degenerative changes were found on H.E.-stained rat pancreatic tissue sections after Fe3+-NTA injection. Histochemical staining, however, showed a reduction in beta-granules and heavy metals (Timm's granules) from islet cells in the central area of the rat pancreatic islet 1 to 3 days after injection of Fe3+-NTA. The fading remained in some islets even at 10 days after injection, but by then the beta-granule distribution was restored in most islet cells. The results indicate a single Fe3+-NTA injection induced transitory instability of the pancreatic islet beta-cell granules and the glucose intolerance with a hyperresponse of IRI.

Seventy-one cases of bronchial asthma were classified into three types: bronchospasm, bronchospasm-hypersecretion and bronchiolar obstruction types. The characteristics of each type were studied in relation to patient age and age at onset of the disease. In the 71 subjects studied, the most frequent type was the bronchospasm type followed by the bronchospasm-hypersecretion type and bronchiolar obstruction type. Intractable asthma was most frequently observed in the bronchiolar obstruction type and least in the bronchospasm type. Most of the patients under 50 years of age showed the bronchospasm type. The bronchospasm-hypersecretion type was characteristically accompanied by blood eosinophilia when the patient age was under 50 years. In the bronchospasm-hypersecretion type, the incidence of intractable asthma was high in patients under 50 years of age, but not remarkable in those over 50. A large proportion of the patients over 50 years of age were of the bronchiolar obstruction type. There was no difference in the incidence of intractable asthma between the two groups classified by age at onset.

A modified method of passive immune hemolysis (PIH) was applied to the quantitative assay of heat-labile enterotoxin (LT) produced by enterotoxigenic Escherichia coli. The method enabled the measurement of 0.2 to 1.2 ng LT. The production of LT by enterotoxigenic E. coli under various conditions was analyzed using the modified method. LT production was intense during the logarithmic growth phase and decreased during the stationary growth phase. Lincomycin (50 to 100 micrograms/ml) affected cell growth slightly, but enhanced production of LT until the late-stationary growth phase. About 90% of the LT produced was retained in the cell, and the rest was excreted into the culture medium. The initial pH of the culture medium affected LT production. Alkaline pH enhanced LT production, though growth was depressed. Aeration enhanced both growth and LT production.

Ten adult cats were anesthetized and ventilated by respirator. After the basilar artery was exposed transclivally and visualized with an operative microscope, mean arterial blood pressure (MABP) was raised gradually by intravenous drip infusion of norepinephrine (5-20 micrograms/kg) or angiotensin-II-amide (0.3-1.0 micrograms/kg). At various blood pressures, microphotographs were taken. There was no appreciable change in vessel diameter at a MABP ranging from 78 to 191 mmHg. The blood pressure was allowed to return to the initial baseline level. Arterial spasm was produced by the topical application of 0.2 M calcium gluconate, which decreased the arterial diameter by 13 to 58 percent for more than 60 min. Blood pressure was increased again after the production of the arterial spasm. Significant increases in the diameter of the arteries were produced by the drug-induced hypertension at levels of MABP ranging from 82 to 192 mmHg. The maximum arterial dilations ranged from 123 to 208 percent of the untreated control. The degree of dilation of the arteries almost paralleled the rise in MABP. Norepinephrine and angiotensin-II had a similar effect on both the blood pressure and the arterial diameter. Induced hypertension would be expected to improve blood flow parameters in the case of spastic cerebral arteries.

A 56 years old male with chronic pancreatitis complained of intractable abdominal pain, anorexia, emaciation and peripheral edema. Medical treatment initiated only partial improvement in the general condition and hypoproteinemia. Endoscopic retrograde cholangiopancreatography revealed multiple filling defects in the dilated main pancreatic duct. Endoscopic aspiration of pure pancreatic juice yielded numerous protein plugs. The endoscopic removal of protein plugs from the pancreatic duct resulted in remarkable improvement in symptoms, laboratory findings and ERCP findings. We consider this procedure to be an important new treatment of chronic pancreatitis.