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Biomedical subjects

M Shirai

Publications and source records attributed to M Shirai.

At least 145 records · Page 8Linked to original sources
PubMed1996

Inhaled nitric oxide: diameter response patterns in feline small pulmonary arteries and veins.

Using an X-ray television system on the in vivo cat lung, we directly measured internal diameter (ID) changes in the small pulmonary arteries and veins (100-1,100 microns ID) in response to 5, 15, and 40 ppm nitric oxide (NO) inhalations. We also measured to what extent 40 ppm NO inhalation can attenuate large ID constrictions at the different serial segments of the small vessels due to unilobar anoxic (0% O2) exposure. Under normoxic conditions, 5-40 ppm NO inhalations significantly increased the ID of both arteries and veins less than approximately 900 microns dose dependently but caused no significant, or only slight, ID increases in the vessels larger than this, if any at all. The ID increase in the serially connected arteries was nonuniform (4-18, 8-28, and 7-35% with 5, 15, and 40 ppm NO inhalations, respectively), whereas that for the veins was relatively uniform (4-9, 6-17, and 7-18% with 5, 15, and 40 ppm NO, respectively). The maximum ID increase occurred in the 200- to 500- and 200- to 700-microns arteries in response to 5-15 and 40 ppm NO, respectively. Unilobar anoxic exposure significantly decreased the ID of the 100- to 700-microns arteries and veins, but not the ID of the other-sized vessels. The ID decrease in the serially connected arteries was nonuniform (13-29%) but relatively uniform in the veins (8-12%). The maximum ID decrease occurred in the 200- to 300-microns arteries. However, adding 40 ppm NO to the lobe completely eradicated the ID decreases at all segments of the arteries and veins and, instead, caused significant ID increase (11-21%) in the arteries and (10-12%) in the veins. The data indicate that, according to dosage, 5-40 ppm NO inhalations cause selective dilation of approximately 100- to 900-microns pulmonary arteries and veins, particularly the 200- to 700-microns arteries. During anoxic exposure, the vasodilator effect of NO is preserved and can completely reverse the marked pulmonary vasoconstriction.

Administration, Inhalation↗
PubMed1996

Effect of maternal adrenalectomy and corticosterone therapy on the early development of B-cells in the fetal pancreatic islet in the rat.

Pregnant Wistar rats were divided into 3 groups, non-operated control, adrenalectomized, and adrenalectomized and corticosterone-treated. Maternal adrenalectomy was performed on day 6 of gestation. Corticosterone therapy was made from the day at operation to the day at observation. The growth pattern of insulin-producing B-cells was observed immunohistochemically and histometrically from days 12 to 16. The results obtained were as follows: From day 12 to day 15, maternal adrenalectomy resulted in a significant retardation of the growth of insulin-positive B-cells in terms of the collective volume of the cells. Maternal corticosterone therapy prevented this retardation. On day 16, however, the growth of B-cells in collective volume overcame the suppressive effect of maternal adrenalectomy. These results suggest that the lack of adrenocortical hormones causes a retardation of B-cell growth in early development, and that, when once developed well, B-cells can grow independently of the hormones.

Adrenalectomy↗
PubMed1996

Time course of ethylene thiourea in maternal plasma, amniotic fluid and embryos in rats following single oral dosing.

Ethylene thiourea (ETU) was administered once orally to pregnant rats on gestation day 12 at a dose of 200 mg/kg, and its concentration-time courses in the maternal plasma, amniotic fluid and embryos were investigated. The ETU concentrations in the maternal plasma and amniotic fluid reached the peak level about 2 hr after dosing, then declined gradually and had disappeared by 48 hr. In embryos, the concentration of ETU peaked at 30 min after dosing and disappeared at 48 hr. The prolonged exposure of the embryos to the high concentration of ETU in the amniotic fluid could be partially responsible for the teratogenic effect of ETU.

Administration, Oral↗
PubMed1996

Morphometric study on the fetal thyroid gland in the nude mouse (BALB/cAnNCrj-nu/nu).

Fetal thyroid glands of athymic nude mice (BALB/cAnNCrj-nu/nu) were examined morphometrically on day 18 of gestation. Compared to euthymic litter mate controls (BALB/ cAnNCrj-nu/+), both the cell height and diameter of thyroid follicles were significantly smaller; fewer well-developed follicles were found in the peripheral region of the thyroid; the body weight and total volume of the thyroid gland were also smaller in nude mice. These results suggest underdevelopment of the fetal thyroid gland of the athymic nude mouse.

Animals↗
PubMed1996

A gene trap strategy for identifying the gene expressed in the embryonic nervous system.

An efficient gene trap strategy was devised for identifying the genes that are expressed in the mouse developing nervous system. Mouse embryonic stem (ES) cell lines that carried independent integrations of a gene trap vector, pSneolN/acZA, were allowed to differentiate in a suspension culture system. To select cells containing neurons, astrocytes or neuron-glia precursors, cell lines were immunohistochemically examined with antibodies against neuron-specific proteins (neurofilament protein 150 kD and microtubule associated protein 2), glial fibrillary acidic protein or nestin. Three cell clones (GT3-8, 11 and 12) were immunoreactive to either of the antibodies employed and at the same time positive for beta-galactosidase activity. When chimeric embryos were generated by the use of the above 3 cell lines, some cells in their nervous system showed X-gal staining. Thus the major advantage of the present gene trap method lies in its prescreening step of manipulated ES cells prior to generation of chimeric animals. This method holds promise as a useful tool for investigating the genes involved in the development of the nervous system.

Animals↗
PubMed1996

Effects of selected organophosphate insecticides on serum cholinesterase isoenzyme patterns in the rat.

The serum cholinesterase (ChE) isoenzyme in rats shows 6 bands after polyacrylamide gradient gel electrophoresis. The effects of organophosphates (fenthion, chlorpyrifos, diazinon, bromophos, propaphos, haloxon, and DFP) on serum ChE isoenzyme bands were studied in 32 male and 32 female 6-w-old Sprague-Dawley rats. Each organophosphate was randomly administered to 4 male and 4 female rats. Blood samples were collected from the abdominal aorta under halothane anesthesia 6 h after dosing. The isoenzyme patterns were determined simultaneously with erythrocyte and serum ChE activities. Changes were observed in all 6 bands of the serum ChE isoenzymes after administration of fenthion, chlorpyrifos and propaphos. Diazinon had no influence on band 6, and DFP and bromophos had no influence on band 5. Haloxon did not effect any of the serum ChE isoenzyme bands. Serum ChE was most suppressed by fenthion, followed by DFP, bromophos, chlorpyrifos, propaphos and diazinon in that order of effect. Serum ChE activity was not suppressed by haloxon. Erythrocyte ChE activity was suppressed by every organophosphate. This experiment demonstrated a correlation between the organophosphate suppression of serum ChE activity and the concentration of serum ChE isoenzyme band 6.

Analysis of Variance↗
PubMed1995

Reaction mechanism of T4 endonuclease V determined by analysis using modified oligonucleotide duplexes.

The reaction mechanism of bacteriophage T4 endonuclease V was investigated using modified oligodeoxyribonucleotide duplexes containing a cis-syn thymine dimer. For the pyrimidine dimer glycosylase step, the formation of a covalent intermediate has been proposed. A fluorine atom was attached to the 2'-position of the 5'-component of the thymine dimer site, which could stabilize the covalent complex and prevent the ring opening of the sugar moiety. The strand cleavage of the 12 base pair substrate analog did not occur, although the glycosyl bond was cleaved by this enzyme. A covalent enzyme--substrate complex was separated by gel electrophoresis under denaturing conditions. It was shown that the enzyme molecules were completely converted to a stable complex in the reaction mixture. Two mechanisms have been proposed for the beta-elimination step. A 12-mer containing a phosphorothioate linkage between adjacent thymidines was prepared. The diastereomers were separated, and the absolute configurations were determined. After formation of the thymine dimer and 32P-labeling of the 5'-terminus, these oligonucleotides were annealed to the complementary 12-mer, and the reaction rates of the pyrimidine dimer glycosylase step and the overall reaction for each duplex were measured under the substrate-saturation conditions. The rate constants indicated that the chemical reaction at the beta-elimination step was rate-limiting. Since no difference was observed in the rate constants for the Rp- and Sp-phosphorothioate substrates, it is concluded that the beta-elimination reaction is catalyzed, not by the internucleotide phosphate, but by an amino acid residue of the enzyme.

Base Sequence↗
PubMed1995

CTL responses of HLA-A2.1-transgenic mice specific for hepatitis C viral peptides predict epitopes for CTL of humans carrying HLA-A2.1.

Vaccine development in animal models depends on ability to recognize epitopes seen by human T cells. In this work, we show that CTL responses in transgenic mice expressing human HLA-A2.1 prospectively predict the same four of 11 hepatitis C virus (HCV) structural protein-derived peptides, expressing a sequence motif for HLA-A2.1 binding, that are actually recognized by human A2.1-restricted CTLs. The CTLs also recognized targets endogenously expressing these proteins. Human CTLs from HCV-infected patients, tested by using the same peptides, revealed a virtually identical response repertoire. A highly conserved HCV core peptide was the most immunogenic, and may be a valuable component of a vaccine against a broad range of HCV isolates in HLA-A2-positive patients. These results suggest that, in spite of species differences, the T cell repertoire is plastic enough to allow a similar response when the same class I MHC molecule is presenting the peptide. Thus, the HLA molecule plays the primary role in determining which peptides are recognized by CTLs. This transgenic mouse model is important for the study of HLA-restricted CTL determinants and for an approach to design a potential HCV vaccine.

Adult↗
PubMed1995

Frequency and significance of antibodies to histones in autoimmune hepatitis.

As part of ongoing studies to define the nature of anti-nuclear antibodies in autoimmune hepatitis and assess their clinical significance, we tested sera from 65 patients who had previously been screened for reactivities to recombinant ribonucleoproteins (U1RNP-A and U1RNP-70K), ribonucleoprotein complexes (52K SSA/Ro and 60K SSA/Ro) and centromere (Cenp-B) for antibodies to histones by enzyme immunoassay. Twenty-three specimens were reactive to histones (35%). Eleven of the 23 seropositive specimens were also reactive to other nuclear antigens (48%); 12 specimens (52%) were reactive only to histone. Histone-reactive sera did not have a characteristic pattern by indirect immunofluorescence. Patients with antibodies to histones were indistinguishable from other by age, gender, clinical and laboratory findings. HLA phenotype, or responses to corticosteroid therapy. Eighteen sera (28%) that had demonstrated nuclear reactivity by indirect immunofluorescence lacked reactivity to the five recombinant nuclear antigens and histones. We conclude that antibodies to histones are common in autoimmune hepatitis and that they are an important species associated with antinuclear reactivity. In some patients, they may be the only findings. Seropositive patients lack distinctive features or different outcomes after therapy. Reactivities against other nuclear antigens probably exist and remain undefined.

Adult↗
PubMed1995

Effects of baroreceptor reflex on efferent pulmonary sympathetic nerve activity in anesthetized cat.

We analyzed the baroceptor reflex effect on efferent pulmonary sympathetic nerve activity (PSNA) in anesthetized cats. PSNA was recorded from the central end of the cut nerve bundle, which was isolated from the lobar artery supplying the diaphragmatic lobe. Renal sympathetic nerve activity (RSNA) and aortic blood pressure (AP) were also simultaneously measured. There were grouped discharges synchronous with cardiac cycle and its respiratory modulation in PSNA. In a given cardiac cycle, the discharge patterns differed between the pulmonary and renal nerves. Average sympathetic nerve activity and AP obtained from 100 consecutive cardiac cycles showed that the baroreceptor reflex delay time on the pulmonary nerve (266 ms) was longer than that on the renal nerve (195 ms). The data indicate nonuniformity in the cardiac-related PSNA and RSNA. The grouped PSNA disappeared with hexamethonium bromide, indicating that PSNA originates from postganglionic efferent fibers. To examine the baroreflex response of PSNA, AP was increased by 70 mmHg with phenylephrine and decreased by 70 mmHg with nitroprusside. PSNA changed inversely to the changes in mean aortic pressure (MAP). In the delta MAP-delta PSNA curve, delta PSNA reached the maximum level (74%) and the noise level at -56 +/- 4 and 58 +/- 4 mmHg, respectively. The mean slope of the curve was 1.5 +/- 0.1%/mmHg. RSNA also responded inversely to the MAP change.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Changes in efferent pulmonary sympathetic nerve activity during systemic hypoxia in anesthetized cats.

Changes in efferent sympathetic nerve activity to the pulmonary vessels during systemic hypoxia have yet to be elucidated. The purpose of this study was to determine the pulmonary sympathetic nerve activity (PSNA) changes in response to acute systemic hypoxia before and after sinoaortic denervation plus vagotomy in anesthetized cats. The denervation was performed to estimate the central nervous system-mediated peripheral chemoreceptor- and baroreceptor-independent PSNA change. PSNA was recorded from the central end of the cut nerve bundle, which was isolated from the lobar artery supplying the diaphragmatic lobe. Renal sympathetic nerve activity (RSNA) and systemic and pulmonary arterial pressures were also measured simultaneously. The animals were submitted to approximately 3-min periods of graded hypoxia (16, 12, 8, 5, and 3% O2 inhalations). PSNA did not change from normoxia down to an arterial O2 partial pressure (PaO2) of approximately 45 Torr (with 12-21% O2 inhalations). Below this level, PSNA began to increase, and markedly so (approximately 2.5-fold) at a PaO2 of approximately 15 Torr (with 3% O2). The hypoxic PSNA increase was significantly larger than that for RSNA, with a PaO2 of less than approximately 30 Torr (with 3-8% O2). Particularly at a PaO2 of approximately 15 Torr, the magnitude of the PSNA increase was two times greater than that for RSNA. After denervation, the hypoxic PSNA increase was significantly attenuated at a PaO2 of approximately 25 to approximately 45 Torr (with 5-12% O2), but the attenuation was very small; therefore most of the PSNA increase persisted. The hypoxic RSNA increase, in contrast, was mostly abolished after denervation. The data indicate that the neural reflex effect of systemic hypoxia on PSNA is significantly greater than that on RSNA and suggest that the hypoxic PSNA increase is mostly mediated by central mechanisms, whereas that for RSNA is chiefly caused by peripheral chemoreceptors.

Animals↗
PubMed1995

The influence of ovarian hormones on the granulomatous inflammatory process in the rat lung.

This study was initiated to clarify the relationship between ovarian hormones and the granulomatous inflammatory process in the lung. To assess whether ovarian dysfunction influences the granulomatous inflammatory process, we compared immunological alterations in ovariectomized rats and in sham-operated rats. After a heat-killed, bacilli Calmette-Guérin (BCG)-elicited granulomatous reaction, the lung-body weight ratios, the number of lymphocytes and activated T-cells, and the interferon-gamma levels in the bronchoalveolar lavage fluid from the ovariectomized rats were significantly higher than those of the sham-operated rats. Moreover, exogenous ovarian steroids supplemented in vivo suppressed not only the granulomatous inflammatory process in the lungs, but also the parameters measured in the bronchoalveolar fluid. These results indicate that ovarian dysfunction may adversely affect the formation of granulomas in the lung.

Animals↗
PubMed1995

Protective effects of prostaglandin E2 on the paraquat-induced constriction of the fetal ductus arteriosus in the rat.

Pregnant rats on day 21 of gestation received a subcutaneous injection of paraquat (25 mg/kg). Two hr later, some fetuses of these rats received a subcutaneous injection of prostaglandin E2 (PGE2). The caliber of the ductus arteriosus (DA) of fetuses was measured 1 hr later. The DA of fetuses of paraquat-treated pregnant rats was significantly constricted compared with that of fetuses of control pregnant rats given physiological saline. However, the DA of PGE2-treated fetuses of paraquat-treated pregnant rats had a caliber comparable to that of control rats. The maternal plasma PGE2 level decreased following paraquat treatment. These results suggest that the decrease of maternal PGE2 level results in a constriction of the DA of fetuses.

Animals↗
PubMed1995

[Effect of inhaled vancomycin hydrochloride on elimination of methicillin-resistant Staphylococcus aureus].

Vancomycin hydrochloride (VCM) is one of the most useful drugs in treating methicillin-resistant Staphylococcus aureus (MRSA) infections. Intravenous administration of the drug is, however, not appropriate in patients with impaired renal or liver function. Thus, we studied the effect of inhaled VCM on MRSA. Fifty-one patients with MRSA in their sputum (35 men and 16 women 21, in the "infected" group and 30 in the "colonized" group, mean age 76.4 years) were studied. MRSA was eliminated in 84.3% of the patients (43 of 51 patients), and the average time required for elimination was 14.7 days. MRSA colonization or infection recurred in 46.5% of the patients (20 of 43 patients), and the duration from elimination until recurrence of MRSA averaged 28 days. Eight patients in whom MRSA was not eliminated by inhaled VCM were not clinically distinguishable from other patients, but their performance status was worse. Two hours after VCM was inhaled, serum VCM concentrations were unmeasurable in 7 patients. The VCM level in sputum peaked at 262.5 micrograms/g just after inhalation, and then gradually decreased. No side effects of this treatment were observed. These results suggest that inhaled VCM can be used to eliminate MRSA.

Administration, Inhalation↗