Biomedical subjects
Publications and source records attributed to Y Matsui.
Varicella-zoster virus was isolated from mononuclear cells from seven immunocompetent children with varicella during the late incubation period and during the acute phase of the disease. The cells from which the virus was isolated were nonphagocytic and did not adhere to the surface of plates. The results indicate lymphocyte-associated viremia at the time of onset of varicella.
Recombinant human tumor necrosis factor (rHu-TNF) was found to exhibit potent antitumor activities not only against murine tumors, i.e. Meth A sarcoma, B 16 melanoma, colon 26 adenocarcinoma, Lewis lung carcinoma and MH134 hepatoma, transplanted in syngeneic mice but also against human tumors, i.e. HMV-2 melanoma, PC-10 lung carcinoma and GOTO neuroblastoma, heterotransplanted in nude mice. rHu-TNF caused necrosis of all tumors tested and inhibited their growth in a dose dependent manner. Complete regression of tumors was observed in mice bearing Meth A, B16, colon 26, MH134, HMV-2 and PC-10 but not in mice bearing Lewis lung carcinoma and GOTO neuroblastoma. The prolongation of survival time was also observed in syngeneic mice transplanted with murine tumors except Lewis lung carcinoma. The antitumor effect of rHu-TNF was more evident when it was given intratumorally than when given intravenously. The feasibility of rHu-TNF as a drug for cancer therapy is discussed.
Although it is well known that the expression of major histocompatibility complex (MHC) antigens on the surface of lymphoblastoid cell lines are cell cycle dependent, the way in which the MHC antigen expression on activated T cells varies with cell cycle phase has not previously been described. Using 11 lymphoblastoid cell lines from malignant and nonmalignant tissues (B cells, T cells, and myeloid cells) and five activated T cell lines (two cell lines activated by phytohemagglutinin and three alloreactive T cell clones), MHC antigen expression was quantitatively studied by dual-beam flow cytometry. Correlated measurements of surface antigen quantity (immunofluorescence), DNA content (Hoechst 33342), and cell size (light scatter), uninfluenced by induction synchrony and cell fixation, were performed. The data indicate that cell surface antigen quantity and cell surface area demonstrate specific values at each phase of the cell cycle when the cells are in logarithmic growth. Examining cells in logarithmic growth, it was confirmed, for all lymphoblastoid cell lines, that the quantity of MHC antigens on G2 (S + G2 + M) cells was greater than that on G1 cells. In addition, it was found, by analyzing antigen quantity and surface area, that class I antigen density in the G2 phase is 17% less than that in the G1 phase in leukemic T cell lines, and that both class I and class II antigen densities in the G2 phase were 21% less than that in the G1 phase in lymphoblastoid B cell lines. In activated T cells, class I antigen density in the G2 phase was 11% less than that in the G1 phase, while class II antigen density in the G2 phase was 12% greater than that in the G1 phase. We describe four important observations in this report. In both G1 and G2 phases, activated T cells express: quantitatively fewer class I antigens than lymphoblastoid B cell lines; similar quantity of class I antigens as that of leukemic T cell lines; and similar quantity of class II antigens as that of lymphoblastoid B cell lines. Also, class II antigens are expressed in greater density in the G2 phase than in the G1 phase in activated T cells. In contrast, lymphoblastoid B cell lines express greater density of class II antigens in the G1 phase than in the G2 phase of the cell cycle. These findings differ from previous reports, suggesting that G1 phase cells may have a more significant role than G2 phase cells as target cells for MHC restricted cytotoxic cells.
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To examine early intercellular junction changes caused by treatment with 9,10-dimethyl-1,2-benzanthracene (DMBA), rat lingual epithelium was cultivated in isolation and observed by electrophysiological, freeze-fracture and whole-mount electron microscopy. Electrophysiological measurements showed a transient decrease in membrane potential of -10.2 mV 6 h after the treatment. It returned to almost the same level as that of the control group 1 day later. Six hours after treatment, input resistance decreased rapidly to 5.3 M omega but increased to 18.0 M omega 12 h after treatment. Transient reduction of input resistance and membrane potential occurred prior to the decrease in the coupling ratio 6 h after treatment with DMBA. In freeze-fracture replicas, the number of gap junctions decreased by approximately 45% of the control value 6 h after treatment with DMBA. At 12 h and thereafter, the number and area of gap junctions subsequently decreased by 60-80% of the control value. Alterations in the number and area of desmosomes were similar to those of the gap junctions. The formation of epithelial cytoskeletons, partially devoid of the 2-4 and 5-8 nm filaments was also observed. A decrease in the density of filament networks beneath the plasma membranes was especially apparent. Treatment with a carcinogen brought about morphological cellular changes as early as 6 h after treatment, and such early changes might trigger metabolic cellular abnormalities. Affected cells appear to move away from normal cells in a process of repeated destruction and revision of intercellular junctions, and cytoskeletons.
Neurons in culture obtained from dissociated cerebral hemispheres of 8-day-old chick embryos showed measurable activities of galactosyl-, fucosyl-, and sialyl-transferases at the external surface of their plasma membrane. Important changes in these activities were observed during cell proliferation and maturation, in particular the surface fucosyltransferase activity, and/or the amount of intracellular fucosylated acceptors increased during synaptogenesis, between 3 and 5 days in culture (d.i.c.). A sodium dodecyl sulfate radioelectrophoretic analysis of the fucosylated neuronal acceptors labelled with [14C]fucose showed, during synaptogenesis, the high labelling of two protein bands of 116 and 50 X 10(3) daltons. The fucosylation of glycoconjugates occurred preferentially, in neurons, upon glycoproteins whereas in glial cell cultures glycolipids were more fucosylated. The reasons for such a difference are not yet understood but the results suggest that the surface fucosyltransferase activity and fucosylated proteins in particular may play a role during the synaptogenesis of neurons in culture.
Monopolar electrical stimulation of the intermediate portion of the solitary nucleus in spontaneously hypertensive rats (SHRs) with cervical cordotomy and vagotomy resulted in a 1.68 times greater increase in plasma vasopressin concentration than in Wistar rats. The result implies that such an enhanced function of the central neural mechanism to release vasopressin in SHR backs up the functionally aberrant cardiovascular receptors.
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The acute hemodynamic effect of the selective alpha1-antagonist, 2-[4-(n-butyryl)-homopiperazine-1-y1]-4-amino-6,7-dimethoxy-quinazoline (bunazosin; E-643), was studied by the microsphere technique in 62 conscious spontaneously hypertensive rats. We found that a large fall in total peripheral resistance with a moderate increase in cardiac output accounted for the moderate decrease in arterial pressure; the heart rate did not change; the skeletal muscle, brain, heart, and gastrointestinal tract sensitively dilated, and kidney less sensitively dilated, their resistance vessels, with little change in their blood flow.
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A Phase II Study of VP-16 was performed in 58 patients with primary lung cancer. VP-16 was administered via infusion at a dosage of 60-100 mg/m2 daily for 5 days, and repeated every 3 to 4 weeks. Of the 58 patients who entered into the study, 38 were evaluable. Partial response was observed in 6 patients who had been diagnosed as having small cell carcinoma of the lung. Response rates were 15.8% for all evaluated patients and 33.3% for the patients with small cell carcinoma of the lung. As for dose-limiting toxicity, leukopenia (less than 3,000/mm3) was observed in 53.1% of cases. Other major adverse reactions were hematologic toxicities such as anemia and thrombocytopenia, gastrointestinal toxicities and alopecia, but these were all well tolerated.
A case of "sclerosing hemangioma" (pneumocytoma) of the lung with lymph node metastasis is reported. A 22-year-old Japanese man was found to have a well-defined round lesion in the right lung (S7), which increased in size slightly during a 2-year follow-up period. He underwent right lower lobectomy with a preoperative diagnosis of a benign lung tumor. The pulmonary tumor revealed histological features characteristic of "sclerosing hemangioma" of the lung, in addition to which there were many large polygonal foamy cells, forming tubular or papillary structures. These cells were found by electron microscopy to contain numerous cytoplasmic lamellar bodies and showed a positive reaction with anti-surfactant apoprotein antibody immunohistochemically. Therefore, they were considered to be cells differentiating toward type II pneumocytes. Review of 21 typical "sclerosing hemangiomas" disclosed a few or some such foamy cells in 10 cases. A single hilar lymph node was the site of microscopic metastases, which consisted of "large clear foamy cells" and smaller polygonal or round cells with slightly eosinophilic cytoplasm, both of which were components of the pulmonary "sclerosing hemangioma." This case supports the theory that "sclerosing hemangioma" is a neoplasm of type II pneumocyte lineage. Although it is said to be benign, rare cases apparently show metastatic potential.
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We studied whether lymphokine-activated killer (LAK) cells were capable of being induced in vitro from peripheral blood lymphocytes (PBL) of patients with malignant glioma, by using recombinant IL-2 (rIL-2). We then investigated whether they possessed anti-tumor efficacy against malignant gliomas (ONS-12, -20, -44). Human LAK cells were generated by placing 5 X 10(6) PBL into each well of 24-well plates (Corning) containing 2 ml of complete medium (CM) with 10 units of rIL-2 (TGP-3, provided by TAKEDA Chemical Industries, Ltd.). The CM consisted of RPMI 1640 with 0.1 mM nonessential amino acids, 1 microM sodium pyruvate, 5 X 10(-5) M 2-mercaptoethanol, 50 micrograms/ml gentamicin sulfate, 0.03% glutamine and 1% heat-inactivated human AB serum. The plates were incubated horizontally at 37 degrees C in a 5% CO2 atmosphere for 72-96 hours. The LAK cells were then harvested, washed three times with Hanks balanced solution, and resuspended in RPMI 1640 with 1% heat-inactivated human AB serum for the in vitro cytotoxicity assays. The anti-tumor cytotoxic activity of LAK cells was estimated in triplicate by 4-hr 51Cr release assays. The cytotoxic activity of the LAK cells against autogeneic ONS-44 glioma cells and PHA blasts was approximately 30% and a few %, respectively. The Natural Killer (NK) activity of the patient with ONS-44 glioma cells was equivalent to that of healthy subject.(ABSTRACT TRUNCATED AT 250 WORDS)
A rare case of primary interhemispheric subdural abscess is reported. This 13 year old boy, who had had high fever for 2 days, was brought into the hospital by an ambulance. He was disoriented and mild stiffness of the neck was noted. A Jacksonian seizure that began in the left leg occurred immediately after admission. The initial CT scan showed no apparent abnormality. His clinical signs and spinal fluid findings showing slight monocytic response and normal sugar content suggested viral meningo-encephalitis. The patient was given steroid and glyceol to control the intracranial pressure and antibiotics was also given. The convulsions disappeared with anticonvulsants and the patient became afebrile on the 7th hospital day. He was discharged on the 53rd hospital day without any neurological deficit. But, he was re-admitted because of recurrence of the convulsion 29 days after the discharge. The CT scan revealed an interhemispheric (rt parafalcial) abscess and the drainage of abscess was performed through a craniotomy. The post-operative course was satisfactory and he was discharged on 33rd post-operative day. It is easy to diagnose the primary interhemispheric subdural abscess on CT scan at the advanced stage. However, it may be difficult to make definite diagnosis at its acute phase and it is important not to miss some characteristic clinical features of the interhemispheric abscess that can be safely cured by appropriate surgical treatment.
Fundamental and clinical studies on a new carbapenem antibiotic, imipenem/cilastatin sodium (MK-0787/MK-0791), were carried out in the field of obstetrics and gynecology. The following results were obtained. The concentration of MK-0787 in uterine tissue was 3.5 approximately 8.2 micrograms/g at about 30 minutes after an administration of 0.5 g/0.5 g of MK-0787/MK-0791 by a 30-minute intravenous drip infusion. The concentration decreased to less than 0.5 microgram/g by approximately 3 hours. The level of MK-0787 in the pelvic dead space exudate reached a peak of 24.0 +/- 4.4 micrograms/ml at 1 hour after an administration of MK-0787/MK-0791 0.5 g/0.5 g and was higher than the plasma level at 1 hour. The level in the pelvic dead space exudate was 2.0 +/- 0.8 microgram/ml at about 6 hours. The MK-0787/MK-0791 was administered to 4 patients with gynecologic infections (2 patients with pelvic peritonitis, 1 patient with salpingitis, 1 patient with a vulvar abscess). The clinical efficacy was good in all 4 patients. Neither adverse effects nor abnormal laboratory findings were observed. It appears that MK-0787/MK-0791 is a safe and useful antibiotic for the treatment of obstetrical and gynecological infections.
Ceftizoxime (CZX) were administered and tested for the efficacy and safety in 80 elderly patients who were older than 65 years of age with infections. The sensitivity of bacteria found in these infections to CZX was examined before the administration of the drug. Serum concentrations and the rate of urinary output of the drug were examined in 3 cases. The clinical effect of CZX was as follows: 29 cases (36.3%) of excellent effectiveness and 31 cases (38.8%) showed moderate effectiveness. The patients were divided into 2 groups depending on the presence or the absence of other diseases in their backgrounds. Effectiveness of CZX for patients with and without other diseases were 74.0% and 85.7%, respectively. The effectiveness of CZX in patients with other diseases in their background was lower than the group without other diseases. Other antibiotics were used in 16 cases before the use of CZX. The effectiveness of CZX for these patients was 62.5%. Infecting bacteria were detected in a total of 46 cases (19 cases of respiratory infections and 27 cases of urinary tract infections). Among the respiratory cases, 8 were due to Gram-positive bacteria and 11 were due to Gram-negative bacteria. No Gram-positive organisms were detected from urinary tract infections, which were all due to Gram-negative bacteria. Sensitivities of isolates of these infecting bacteria to CZX were very sensitive 3 isolates, sensitive (++) 8 and slightly sensitive (+) 1 isolate. It was found that CZX was effective against 39 of 46 cases from which causative organisms were identified. The effectiveness ratio was 84.8%. Serum concentration of CZX was determined after a drip injection of 1 g CZX for 1 hour. The half-lives of CZX in plasma in healthy subjects and aged patients were 1.33 hours and 2.15 hours, respectively. The rate of urinary output of CZX during 6 hours after the injection was 76.4% in healthy subjects. Delayed urinary output which was 58.2% during 7 hours after injection was observed in aged patients. Fever in 1 patient and eosinophilia in 3 cases were observed after administration of CZX.
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