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Biomedical subjects

K Hirota

Publications and source records attributed to K Hirota.

At least 235 records · Page 13Linked to original sources

Developmental changes of neutral glycosphingolipids as receptors for pulmonary surfactant protein SP-A in the alveolar epithelium of murine lung.

A dramatic change in the glycosphingolipid composition in murine lung occurred between 1 day and 1 week after birth. GlcCer and LacCer were the predominant neutral glycosphingolipids prenatally and 1 day after birth, and the concentrations of globo- and ganglio-series glycosphingolipids increased abruptly from 1 week after birth, reaching maxima at 2-3 weeks. To explore the functional significance of the change, we examined the role of neutral glycosphingolipids as receptors for the murine pulmonary surfactant protein, SP-A, and found that SP-A bound to LacCer, Gg3Cer, and Gg1Cer, but not to Gb3Cer, Gb4Cer, IV3GalNAc alpha-Gb4Cer, sulfatide, or several gangliosides. On TLC-blotting with 125I-labeled SP-A, the binding of SP-A to Gg3Cer and Gg4Cer was 5 times higher than that to LacCer, and on immunohistochemical staining Gg4Cer and Gg3Cer was mainly observed in the alveolar epithelium. Thus, the capacity to retain SP-A of glycolipid receptors per gram dry weight of lung at 1 week after birth was 1.6 times higher than that at 1 day after birth, and reached a maximum 3 weeks after birth. These findings suggest that the enhanced synthesis of the ganglio-series neutral glycosphingolipids 1 week after birth results in an increase in the binding capacity for SP-A on the epithelial cell surface of alveoli.

Animals↗

Motor and sensory disability has a strong relationship to induction dose of thiopental in patients with the hypertropic variety of Charcot-Marie-Tooth syndrome.

In a prospective study, we determined the anesthetic induction dose of thiopental and the clinical variables influencing the appropriate induction dose of thiopental in 20 patients with the hypertrophic variety of Charcot-Marie-Tooth syndrome (CMT). As controls we chose 50 patients without CMT. Motor disturbance was evaluated in terms of muscle weakness of the distal lower and upper extremities. We examined sensory disturbance by evaluating loss of sensation in the index finger and great toe. The preinduction cardiac output was measured by echocardiography. Anesthesia was induced with repeated injections of 50 mg thiopental. The minimum induction dose of thiopental (MID) was confirmed when the eyelash reflex ceased. We maintained anesthesia with enflurane and nitrous oxide. The 95% confidence interval of the MID in patients used as the controls was 2.5-4.9 mg/kg. The MID in 11 patients with CMT was less than 2.5 mg/kg. MIDs in the patients with CMT were significantly smaller than those of the control patients (P < 0.0001). Also we found a strong relationship between the MID and the severity of both motor and sensory disturbances (P = 0.003 and 0.002, respectively). There was no relationship between the MID and other clinical variables, such as age, gender, inherited type, body weight, and preinduction cardiac output. Because delay in the recovery from anesthesia can be caused by an inappropriate dose of thiopental in CMT patients in whom motor and sensory function is seriously impaired, the dose of thiopental probably should be reduced and based on the individual patient's response.

Adolescent↗

Isoflurane and sevoflurane modulate inactivation kinetics of Ca2+ currents in single bullfrog atrial myocytes.

BACKGROUND: To clarify the mechanism(s) of anesthetic depression of myocardial Ca2+ currents, the effects of isoflurane and sevoflurane on the inactivation kinetics of Ca2+ current in single bullfrog atrial myocytes were studied. METHODS: Freshly isolated bullfrog atrial myocytes were obtained with an enzymatic dispersion procedure. Ca2+ currents were recorded with a whole-cell voltage-clamp technique. RESULTS: Both isoflurane (1.25, 2.5, 5.0 vol%) and sevoflurane (2.5, 5.0 vol%) decreased the peak amplitude of Ca2+ current ICa with a minimal change in the time to peak and the reversal potential. The inactivation kinetics studies revealed that (1) isoflurane (2.5 vol%) and sevoflurane (5.0 vol%) markedly reduced the time constant of inactivation in ICa to 55% and 75% of control, respectively; (2) isoflurane (2.5 vol%) shifted the midpoint (V1/2) of steady-state inactivation curve of ICa toward negative by 2.3 mV; and (3) isoflurane (2.5 vol%) delayed the reactivation time constant of ICa to 119% of control. The further computer-simulation study demonstrated that the observed decrease of time constant by isoflurane (1.25, 2.5 vol%) and sevoflurane (2.5 vol%) can explain the reduction in amplitude of ICa. CONCLUSIONS: The depression of ICa by lower concentration of isoflurane (1.25, 2.5 vol%) and sevoflurane (2.5 vol%) mainly is due to the decrease of time constant and, at higher concentration, isoflurane and sevoflurane may affect the other membrane components.

Anesthetics, Inhalation↗

Possible role for a polysaccharide antigen shared between Streptococcus pyogenes and S. mutans in the pathogenesis of poststreptococcal glomerulonephritis.

Streptococcus mutans has been shown to share a polysaccharide (PS) antigen with S. pyogenes strains isolated from patients with acute poststreptococcal glomerulonephritis (PSGN), using a monoclonal antibody f-77 reactive with the PS. To investigate the pathogenetic role of the shared PS in PSNG, experimental nephritis was induced in animals. Rats were immunized thrice with heat-killed cells of S. mutans or S. pyogenes, followed by an intravenous injection of live cells of S. pyogenes. Histologic examination showed that both animal groups had comparable degrees of diffuse proliferative nephritis characterized by immune deposits. The shared PS antigen was detected in glomeruli of all nephritic rats by immunofluorescence using monoclonal antibody f-77. Furthermore, all nephritic rats had an elevated antibody titer to the shared PS antigen. These results suggest that prior sensitization (infections such as dental caries) to S. mutans modulates immune responses to subsequent S. pyogenes infections and induces immune-complex disease (PSGN) through the shared PS antigen.

Acute Disease↗

[Prevention of infections in a case with myelodysplastic syndrome by an intermittent subcutaneous administration of G-CSF].

An 83-year-old male was admitted to our hospital because of pancytopenia and low grade fever on April 19, 1993. On admission, hematological data were as follows: WBC 1,000/microliters with 19% neutrophils, RBC 367 x 10(4)/microliters, Hb 9.5 g/dl and platelets 6.7 x 10(4)/microliters. Bone marrow examination revealed 6.6% myeloblasts and 33.5% erythroblasts. Morphological abnormalities included hypersegmentation, degranulation and pseudo-Pelger's nuclear anomaly in neutrophils. Based on these findings the diagnosis of refractory anemia with excess of blasts (RAEB) of the myelodysplastic syndrome (MDS) was made and therapy with low dose Cytarabine (Ara-C) was initiated in April 1993. The patient had two episodes of severe pneumonia in June and July. Therefore, 75 micrograms/day of G-CSF was given in addition to antibiotic therapy for the second episode of infection in July. Thereafter the severe infection subsided, and G-CSF administration was switched to an intermittent schedule (75 micrograms twice a week) since September. Cytarabine ocfosfate (100 mg/day) was added for 10-14 days at interval 1-2 months from October,1993. He has been well with no episode of infection for more than two year. One major concern regarding the clinical application of G-CSF in MDS patients is related to the possible stimulation of leukemic cell proliferation. Frequent hematological monitoring is necessary in patients with RAEB who are prone to develop acute myeloid leukemia. However, we administered G-CSF at a relatively low dose twice a week for over two year and could successfully prevent infections without inducing the leukemic changes.

Aged↗

[Development of a detection system for Helicobacter pylori DNA in gastric juice].

A rapid and sensitive PCR-based microwell plate assay (PCR-MWP) system to detect the 16 S ribosome RNA gene of Helicobacter pylori was developed. Analytical sensitivity, evaluated with purified recombinant plasmid DNA and genomic DNA of H. pylori, was one copy of DNA per PCR. Specificity was validated with a panel of DNA from 75 kinds of microorganisms including Helicobacter showed weak positives, when 1 pg of DNA was input. Other microorganisms gave negative signals even when 100 pg of DNA was used for PCR. When compared with a Nested-PCR system to detect the urease A-subunit gene performed by a commercial reference laboratory, the results obtained (sensitivity 93.3% and specificity 73.3%) was almost equivalent. The PCR-MWP was rapid and easy for the detection of H. pylori DNA in gastric juice specimen.

DNA, Bacterial↗

Endotoxin activates a chemokinergic neuronal pathway in the hypothalamo-pituitary system.

Cytokines play a critical role in the cascade of events that cause septic shok. One regulatory system suggested to be important in controlling inflammatory response is the neuroendocrine axis. One of the chemokines is cytokine induced neutrophil chemoattractant (CINC), which was first described as an immuno-modulator of peripheral tissue in inflammatory responses. To assess further the contribution of the chemokine to the central nervous system, we performed immunohistochemistry on rat brains and found strong CINC-like immunoreactivity in the posterior pituitary gland. Treatment with bacterial endotoxin (lipopolysaccharide; LPS) markedly enhanced CINC-like immunoreactivity in the posterior pituitary. Before the LPS challenge, signal for CINC mRNA was undetectable in the paraventricular hypothalamic nucleus (PVN). The LPS challenge induced strong hybridization signals of CINC mRNA in the parvocellular and magnocellular subdivision of the PVN within 15 minutes (min) and peaked at 30 min. The LPS challenge provoked no observable change in the supraoptic nucleus. These studies demonstrate the presence of an endotoxin-sensitive chemokinergic neuronal pathway in the hypothalamo-neurohypophysial system and this newly-described pathway will provide a novel information to understand another possible neuralimmune mechanism.

Animals↗

[Effect of estriol and bone mineral density of lumbar vertebrae in elderly and postmenopausal women].

To compare the efficacy of estriol (E3) in postmenopausal and senile osteoporosis, we administered orally 1 g/day calcium lactate either alone (control groups) or with 2 mg/day estriol (estrogen groups) for 10 months to 20 postmenopausal women aged 50-65 years and to 29 elderly women aged 70-84 years, and measured their bone mineral density of the lumbar vertebrae by dual energy X-ray absorptiometry. Out of 41 subjects who completed 10 months of treatment, 8 postmenopausal women and 12 elderly women in the estrogen groups had significant (p < 0.05) increases in bone mineral density (5.59 +/- 4.79% of the respective basal values). Ten postmenopausal women and 11 elderly women in the control groups had decreases bone mineral density (-4.02 +/- 7.00% and -3.26 +/- 4.60% of the respective basal values) at the 10th month. Genital bleeding as a side effect of estriol was seen in 6 out 29 elderly subjects at this dose. Moreover, decreases in the levels of calcium, total cholesterol, and triglycerides in serum, and an increase in the level of high-density lipoprotein-cholesterol were seen only in the elderly women receiving estriol. Although a lower dosage of estriol may be recommended for elderly subjects, these observations suggest that hormone replacement therapy with estriol is effective against degenerative osteoporosis, and that low-turnover bones in elderly women are also responsive to estriol.

Aged↗

[Difficult tracheal intubation and abnormal response to thiopental in a patient with arthrogryposis multiplex congenita].

Anesthesia was administered for six times to a patient with arthrogryposis multiplex congenita (AMC) at the age of 10 to 17 years. In the first four occasions of anesthesia, difficult tracheal intubation was encountered due to limited neck extension, inadequate mouth opening and the short epiglottis. On the fifth anesthesia, the patient remained conscious even after intravenous injection of thiopental 6.6 mg.kg-1, and enflurane in combination with nitrous oxide was administered to induce anesthesia. During the induction of the sixth anesthesia, excessive oral secretion and severe continued nausea were observed just after intravenous administration of thiopental 5.3 mg.kg-1. These were overcome by intravenous administration of ketamine 2.0 mg.kg-1. Problems such as difficulty in tracheal intubation and abnormal response to thiopental need special attention in patients complicated with AMC, particularly during induction of anesthesia.

Abnormalities, Multiple↗

[Channel structure and functioning based on octagonal structure model].

On the basis of the sequence comparison of squid sodium channel SQSCl with those of other channels, we have proposed a tertiary structure model of the sodium channel where the transmembrane segments are octagonally aligned and the four linkers of S5-6 between segments S5 and S6 play a crucial role in the activation gate, voltage sensor and ion selective pore, which can slide, depending on membrane potentials, along inner walls consisting of segments S2 and S4 alternately. The proposed octagonal structure model is contrasted with that of Noda et al (Nature 320 : 188-192, 1986) and with Durrel and Guy (Biophys J 62 : 238-250, 1992). The octagonal structure model can explain the gating of activation and inactivation, the ion selectivity, and as well, the action mechanism of both tetrodotoxin (TTX) and a-scorpion toxin (ScTX), and be applied not only to the sodium channel, but also to the calcium channel, potassium channel, cGMP gated channel and further to the inwardly rectifying K channels. However Yan and Horn have discussed voltage dependent S4 movement in sodium channels from the accessibility of methanethiosulfonate (MTSET) to cystein residue which was substituted for the outermost arginine in IVS4 (Neuron 15 : 213-218, 1995), the neutralization of the arginine was revealed not to influence the activation of the channel. It suggest that the residue in the 3rd position of IVS4 is not a part of the voltage sensor located in the membrane. These result suggest that the change of the accessibility might be caused by the change of the covering of the residue rather than the movement of S4.

Amino Acid Sequence↗

Rapid bone resorption adjacent to hydroxyapatite-coated implants.

This paper describes rapid bone resorption in the peri-implantitis of HA implants based on both our clinical observations of and histological research on extracted dense hydroxyapatite (HA) implants. The surfaces of extracted HA implants were rough, although they were smooth at fixture placement. Plaque formed on the necks of the implants, whereas little plaque was seen on the bottoms. The plaque consisted of cocci and rods, including filamentous bacteria. Few spirochetes were observed. Although surrounding bone was formed rapidly around the HA implant, bone thickness gradually decreased compared with the titanium implant. These facts suggest that the rigid biointegration of HA with the thin surrounding bone--that is, the overstressing of the bone--causes rapid bone resorption rather than plaque accumulation on HA.

Adult↗

Diagnosis of HIV-1 infection with whole saliva by detection of antibody IgG to HIV-1 with ultrasensitive enzyme immunoassay using recombinant reverse transcriptase as antigen.

Whole-saliva samples were collected from 45 asymptomatic carriers, 18 patients with AIDS-related complex (ARC) or AIDS, and 76 medical students by simple spitting with no stimulation and tested by an ultrasensitive enzyme immunoassay (immune complex transfer enzyme immunoassay) for anti-HIV-1 IgG using recombinant reverse transcriptase as antigen and beta-D-galactosidase as label. With as little as 1 microliter of whole saliva, the lowest signals among the 45 asymptomatic carriers, 8 patients with ARC, and 10 patients with AIDS were 38-, 78-, and 3-fold, respectively, higher than the highest signal among the medical students. When the volume of whole saliva for test was increased up to 100 microliters, no significant effect was observed on signals for seropositive cases and signals for the medical students increased only very slightly. Therefore, whole-saliva samples containing extremely low levels of anti-HIV-1 IgG, even 2,000-fold lower than the lowest level among the 45 asymptomatic carriers tested, were considered to be discriminated from those of seronegative individuals. Thus, the sensitivity and specificity were expected to be both 100% with whole saliva even for a larger number of samples, although the number of samples tested was limited.

Adolescent↗

Opposite effects of transforming growth factor alpha and epidermal growth factor on mouse placental lactogen I secretion.

This study was undertaken to determine whether transforming growth factor alpha (TGF-alpha) regulates the production of mouse placental lactogen I (mPL-I) and mPL-II in a manner that is similar to that of epidermal growth factor (EGF), which was previously shown to stimulate mPL-I secretion and inhibit mPL-II secretion. In contrast to the activity of EGF, human (h) and rat (r) TGF-alpha (each at 100 ng/ml) inhibited secretion of mPL-I by placental cells isolated from mice on day 7 of pregnancy. Maximum inhibition of mPL-I secretion occurred on the third day of a 5-day culture period and ranged between 37% and 56% in multiple trials. Incubation of cells with hTGF-alpha and EGF was not followed by a change in the mPL-I concentration of the medium, suggesting the peptides antagonized each other's effects. hTGF-alpha and rTGF-alpha inhibited secretion of mPL-II; maximum inhibition ranged between 62% and 84% in multiple trials. The lowest concentrations of hTGF-alpha that affected mPL-I and mPL-II secretion were 10 ng/ml and 1 ng/ml, respectively. EGF and hTGF-alpha bound to the same receptors on placental cells, as assessed by cross-linking, and both peptides stimulated receptor phosphorylation, as assessed by Western blot analysis. There are three types of mPL-containing cells in placental cultures: cells that contain only mPL-I, cells that contain only mPL-II, and cells that contain both mPLs. The percentage of each type of mPL-containing cell in the culture was determined by immunostaining. hTGF-alpha affected the differentiation of the subpopulations of PL-containing cells in a manner that differed from that of EGF. The data suggest that TGF-alpha and EGF do not regulate the production of mPL-I and mPL-II in a similar manner.

Animals↗