Antigenic and restriction endonuclease analyses of new adenovirus types 19 and 37 causing acute conjunctivitis

DNA restriction endonuclease cleavage analysis and serum neutralization test were performed in strains of adenovirus types 19 (Ad-19) and 37 (Ad-37) isolated from patients with acute conjunctivitis in Sapporo (Japan), Kaohsiung (Taiwan) and Pusan (South Korea) during the period of 1977 to 1984. Ad-19 and Ad-37 could be roughly differentiated, but a fair degree of cross reactivity was noted by serological test. By DNA restriction endonuclease analysis, Ad-19 isolates, Ad-19 prototype strain and Ad-37 strains were clearly differentiated. It was suggested by DNA cleavage patterns that both Ad-19 and Ad-37 isolates in East Asia are the same as those currently found in Europe and the USA. A new subtype of Ad-37 was found by DNA cleavage analysis among the isolates obtained in Sapporo and Kaohsiung in 1980.     

The adsorption of endotoxin molecule in a microporous polyethylene hollow fibre membrane.

The microporous polyethylene hollow fibre membrane is capable of adsorbing small-sized lipopolysaccharides (LPS) prepared by sonication dispersion, column chromatography on Sephadex G-75 and filtration through a filter membrane with a nominal pore size of 0.025 micron. Small-sized LPS had a one-thousandth of endotoxin activity as compared to intact LPS, when determined by the Synthetic Chromogenic Substrate method of LAL with a specific endotoxin activity of 73.7 ng/micrograms LPS. Fluorescent microscopy of fluorescein conjugated LPS on a microporous polyethylene hollow fibre showed that fluorescein-LPS was adsorbed through the entire depth of the membrane texture. Accordingly the adsorption capacity of the filter for small-sized LPS was determined as 1.65 mg LPS/3.68 m2 surface/116 mg fibre/module.     

Increased activity of oligo-2'',5''-adenylate synthetase in Down''s syndrome and epilepsy.

The level of oligo-2',5'-adenylate synthetase activity is a good marker for the response of cells to interferon. This enzyme can polymerize ATP to form oligonucleotides in the presence of double-stranded RNA, i.e. polyinosinate-cytidylate in vitro. The activity of this enzyme in peripheral blood mononuclear leucocytes was significantly increased in Down's syndrome (P less than 0.01) and epilepsy (P less than 0.01) compared with that in healthy controls, but the increase of activity was not significant in multi-infarct dementia (MID) (P greater than 0.05). Although the patients with Down's syndrome showed higher levels of this enzyme activity than the controls, interferon activity was never detected in the circulation. In addition, the serum of patients with Down's syndrome lacked the capacity to induce this enzyme in NC-37 and FL cells, and furthermore it was shown that the inhibitor of interferon activity was not found in the serum of patients. This discrepancy in Down's syndrome may be the result of the hypersensitivity of cells to interferon. On the contrary, interferon activity (32 IU/ml) was detectable in the circulation of one patient with epilepsy, and the serum of this patient had the capacity to induce this enzyme in NC-37 and FL cells.     

Coexpression of adult T-cell leukemia-derived factor, a human thioredoxin homologue, and human papillomavirus DNA in neoplastic cervical squamous epithelium.

Adult T-cell leukemia-derived factor (ADF) is an autocrine interleukin-2 receptor-inducing factor produced by human T-lymphotropic virus-1 (HTLV-1)-transformed lymphocytes, which has a high structural homology with an endogenous dithiol reducing coenzyme, thioredoxin. Its localization was investigated immunohistochemically in the cervix, using normal tissue (27 samples) and squamous neoplastic tissue (three condylomas, 42 cervical intraepithelial neoplasia [CIN] samples, 34 invasive squamous cell carcinoma samples). The expression of human papillomavirus (HPV) DNA was also studied in serial sections of the same subjects. Normal squamous cells and glandular cells of the cervix were negative for ADF. However, intracytoplasmic and/or intranuclear ADF-positive cells were usually found in the intermediate and superficial layers of the neoplastic squamous epithelium of condylomas (three of three cases) and CIN (35/42 cases). HPV DNA was detected in all condylomas and in 27 of 42 CIN specimens. HPV DNA-positive cells were usually localized in the intermediate and superficial layers of the neoplastic squamous epithelium. These HPV DNA-positive cells were also positive for ADF. Invasive squamous cell carcinoma was also positive for ADF (24/34 cases) and HPV DNA (11/34 cases). The coexpression of HPV DNA and ADF was observed in all HPV DNA-positive cases. Coexistence of HPV DNA and ADF immunopositivity in neoplastic squamous cells of the cervix suggests that ADF expression closely reflects the intracellular event on HPV DNA replication.     

Tumor induction in mice administered neonatally with 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole or 3-amino-1-methyl-5H-pyrido[4,3-b]indole

3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) or 3-amino-1-methyl-5H-pyrido[4,3-b]mdole(Trp-P-2), which is a potent mutagen from pyrolysates of tyrptophan,was given subcutaneously to neonatal ICR mice, and all animalswere observed for 1 year. Tumors of the livers and lympho-retkulartissue were induced. In the mice given Trp-P-1, the incidencesof these tumors were as follows: liver tumors in 45% of themales; malignant lymphoma in 13% of the males and in 24% ofthe females. In the mice given Trp-P-2, the incidences of livertumors in the males were dose-dependent (12.5 mg/kg, 12%; 25mg/kg, 18%), while those of malignant lymphoma varied withina range from 5 to 19%. Statistical analysis revealed that theincidences of the liver tumor in the mke given Trp-P-1 or Trp-P-2and those of lymphoma in the mice given Trp-P-1 were significantlyhigher than those of the controls. In the control mice, theincidences of tumors were as follows: malignant lymphoma in5% of the females; lung tumor in 14% of both sexes.     

Antiemetic effects of combinations of metoclopramide, droperidol and dexamethasone for the prevention of cisplatin-induced gastro-intestinal toxicity: a randomized crossover trial

Thirty-two patients with primary lung cancer receiving combination chemotherapy including cisplatin at a dosage of 80-120 mg/m2 were entered into an antiemetic randomized crossover trial. Patients received metoclopramide (2 mg/kg i.v. every 2 h X 5), droperidol (0.5 mg/kg i.v.) and dexamethasone (30 mg i.v.) on day 1, and metoclopramide (1mg/kg i.v. every 8 h X 3) (Regimen A) or metoclopramide and droperidol (2.5 mg i.v. every 8 h X 3) (Regimen B) on days 2 to 5. No vomiting occurred within the first 24 hours after cisplatin administration in 75% of patients. Regimen B was found to be more effective than regimen A with respect to the mean duration of vomiting (p less than 0.1), the mean duration of nausea (p less than 0.05), the mean duration of anorexia (p less than 0.05), and the mean score of the patients' opinions (p less than 0.1). When the patients were asked for their opinion of the two regimens, 39% preferred regimen B (p less than 0.05). There were no major side effects with either regimen.     

The Chronological changes in the cerebral blood flow and cerebral metabolic rate for glucose in the ischemic rabbit brain

Chronological changes in regional cerebral blood flow (rCBF) and in the regional cerebral metabolic rate for glucose (rCMRGlu) were studied by a double tracer autoradiographic method in regions of local ischemia in rabbit brains. Local ischemia was produced by cautery of the bilateral vertebral artery, followed several days later by cautery of the left middle cerebral artery through a transorbital approach and ligation of the left common carotid artery. Autoradiography was performed, 2 hours, 6 hours, and 4 days after occlusion, by a double tracer method involving the use of 14C-iodo-antipyrine and 18F-fluoro-deoxyglucose. Absolute rCBF values were estimated by Sakurada's method and rCMRGlu values by Hutchins' formula. Histological examination was performed concurrently with the rCBF and rCMRGlu study. Mildly ischemic lesions (rCBF of 25 to 40 ml/100 g/min) were detected in the superior portion of the left frontal lobe, the left parietal lobe, and the left occipital lobe. Severely ischemic lesions (rCBF below 25 ml/100 g/min) were found in the lateral part of the left frontal lobe, the left temporal lobe, and the left caudate nucleus. In the mildly ischemic regions, rCMRGlu decreased in proportion to the decrease in rCBF. That is, matched low perfusion was observed, but there were no histological abnormalities. In severe ischemia the situation was quite different. Two hours after occlusion, most areas showed a decrease in rCMRGlu in proportion to the decrease in rCBF. However, 6 hours after occlusion, rCMRGlu decreased nonuniformly: in some places the decrease was dramatic and in others, rCMRGlu residue was found. Four days after occlusion, the reduction in rCMRGlu was again proportional to the rCBF decrease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical evaluation of sulbactam/ampicillin in the pediatric infections

Sulbactam/ampicillin (SBT/ABPC) was administered to 33 pediatric inpatients with 34 bacterial infections. Clinical efficacies were judged to be good in 33 cases (97.1%) out of 34 which included 13 cases of 14 with infections caused by beta-lactamase-producing strains of organisms, and successfully cured by this drug. There were no particular side effects to comment except some cases of diarrhea and loose stool. These results indicated that SBT/ABPC would be useful in the treatment of pediatric infections as a first choice of drug. Serum half-lives of ABPC and SBT were 0.79 hour and 1.02 hours, respectively, hence, q.i.d. dosage regimen would be appropriate.     

Dissociation of various biological activities of Clostridium perfringens alpha toxin by chemical modification

The effect of N-acetylimidazole, tetranitromethane, maleic anhydride and N-ethylmaleimide on various biological activities of Clostridium perfringens alpha (alpha)-toxin was investigated. Treatment of the toxin with N-acetylimidazole, tetranitromethane or maleic anhydride resulted in significant reduction of lethal, hemolytic and platelet-aggregating activities and phospholipase C activity (EY activity), as measured by increased turbidity in egg yolk emulsions. However, EY activity was more resistant to these reagents than lethal, hemolytic or aggregating activities. Phospholipase C activity (PN activity) as measured by hydrolysis of p-nitrophenylphosphorylcholine was retained after treatment with N-acetylimidazole, tetranitromethane or maleic anhydride. The activities of the toxin were not inactivated by treatment with N-ethylmaleimide. These data suggest that alpha-toxin contains multiple sites for biological activities of the toxin.