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Biomedical subjects

K Ohta

Publications and source records attributed to K Ohta.

At least 541 records · Page 30Linked to original sources

Involvement of neuronal cell surface molecule B2 in the formation of retinal plexiform layers.

The B2 molecule is a 220 kd neuronal cell surface protein of Xenopus, recognized by monoclonal antibody B2 (MAb B2). Immunohistochemistry using MAb B2 revealed that the B2 molecule was expressed in both the inner and outer plexiform layers within the neural retina. During development of the neural retina, the B2 molecule first appeared at stages 35/36 in the newly formed plexiform layers. When embryonic eyes were cultured in the presence of anti-B2 antiserum (Fab fragments), the formation of the retinal plexiform layers was impeded. These data suggest that the cell surface molecule B2 plays a role in the development of retinal plexiform layers.

Animals↗

Hypoxia modulates mediator responses and neurotransmission in guinea-pig trachea in vitro.

To discover whether hypoxia affects mediator responses and neurotransmission in tracheal smooth muscle, we studied in vitro tracheal segments from guinea-pigs under isometric conditions. Hypoxia itself did not alter the basal tone. The maximum response to acetylcholine and histamine under hypoxia was less than that under oxygenated conditions. The logarithm of 50% effective concentration (log EC50) of the response to acetylcholine under hypoxia was not altered, but the log EC50 of the response to histamine decreased significantly. In contrast to the response to exogenous acetylcholine, the maximum contractile response to electrical field stimulation (EFS) under hypoxia was not different from that under oxygenated conditions, but the logarithm of 50% effective frequency of contractions caused by EFS under hypoxia decreased significantly. On the other hand, non-adrenergic-non-cholinergic relaxation caused by EFS was unaffected by hypoxia. These observations suggest that hypoxia can modulate the responses of tracheal smooth muscle to acetylcholine, histamine and nerve stimulation.

Acetylcholine↗

Exploratory eye movements and neuropsychological tests in schizophrenic patients.

Exploratory eye movements in schizophrenic and nonschizophrenic subjects were examined with an eye mark recorder while the subjects viewed geometric figures. Elementary components of eye movements and the responsive search score (RSS), a function of the number of sections on which the subjects fixated, were measured by means of an eye movement analyzer and slow motion replay. The schizophrenic group and the depressed patient group had fewer eye fixations than the normal control group and the obsessive-compulsive disorder group. The schizophrenic group had a lower RSS average than patients with depression, patients with obsessive-compulsive disorders, or subjects in the normal control group. These results in conjunction with those of our previous studies suggest that a low RSS is specific to schizophrenia. We examined the relationship between these eye movements and neuropsychological tests and also investigated the relation between the eye movements and clinical symptoms by means of the Brief Psychiatric Rating Scale, Schedule for Affective Disorders and Schizophrenia, and the Scale for the Assessment of Negative Symptoms. The RSS correlated positively with the performance IQ and Wechsler's Maze test, but not with the Wisconsin Card Sorting Test or the verbal IQ result. The RSS also correlated negatively with negative symptoms. These results suggest that the RSS has two characteristic features: it is strongly associated with the interpersonal response and it may be connected with visuospatial and visuomotor functions including attention.

Adult↗

VO2 and VCO2 following tourniquet deflation.

We examined changes in O2 uptake, CO2 output, blood pressure and heart rate following tourniquet deflation in 23 patients undergoing orthopaedic surgery of the lower extremities. A pneumatic tourniquet was applied for periods ranging from 21 to 106 min (mean 51 min). Prerelease values of VO2 (O2 uptake at each min) and VCO2 (CO2 output at each min) were 201 (37) and 174 (38) (mean (SD)) ml.min-1, respectively. Significantly, VO2 and VCO2 increased by 55% and 80%, respectively, at 2 min after tourniquet release and returned to prerelease values within 8 min. The blood pressure fell significantly and the heart rate rose significantly. The increases in CO2 output and O2 uptake were dependent on the length of tourniquet inflation time; Y = 4.7 x (tourniquet time) + 54, r = 0.88, (p less than 0.001) for CO2, and Y = 1.3 x (tourniquet time) + 99, r = 0.52, (p less than 0.05) for O2. The slope of the increase in CO2 output as a function in inflation time was 3.6 times greater than that of O2 uptake. In conclusion, CO2 output and O2 uptake increased transiently after tourniquet deflation and the extent of the increase in CO2 output is more than threefold as compared with that in O2 uptake.

Adolescent↗

Haemopoietic growth factors induce human basophil migration in vitro.

Accumulation of basophils in inflammatory sites is an important aspect of the late-phase allergic reaction involving skin and upper and lower airways, suggesting the existence of mechanisms for basophil migration. Because haemopoietic growth factors have been shown to stimulate various functions of human basophils, we tested the ability of haemopoietic growth factors to migrate basophils in vitro. Both IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) induced migration of purified normal basophils (purity c. 80%) in a dose-dependent fashion at picomolar concentrations, while granulocyte (G)-CSF, macrophage (M)-CSF, and IL-4 had no effect at all. Chequerboard analyses indicate that migratory activity of both factors are chemokinetic. These results suggest that local production of both factors during allergic reactions might potentially play an initial role in the recruitment of basophils from the circulation to sites of inflammatory reactions.

Antibodies↗

L-arginine infusion induces hypotension and diuresis/natriuresis with concomitant increased urinary excretion of nitrite/nitrate and cyclic GMP in humans.

1. The vascular endothelium produces endothelium-derived relaxing factor (EDRF) or nitric oxide (NO), which exerts vasodilation through cyclic guanosine monophosphate (cGMP) as a second messenger. To determine whether EDRF has any vasodilating and natriuretic action in man, the present study examined the effects of L-arginine (L-Arg), a substrate for NO, on the responses of mean blood pressure (MBP) and heart rate (HR); plasma concentrations of cGMP, atrial natriuretic factor (ANF) and nitrite/nitrate (NOx); urinary excretion of sodium, cGMP and NOx; and urinary flow in eight normal male subjects. These parameters were compared with those following saline infusion in the same subjects. Clearance of para-aminohippuric acid (PAH) and inulin was studied in five normal subjects. 2. Infusion of L-Arg (30 g) caused a significant fall in MBP (-8 mmHg) with a concomitant rise in HR (10 beats/min), while saline infusion had no effects on these parameters. 3. Neither L-Arg nor saline infusion caused appreciable changes in plasma concentrations of ANF or NOx. Plasma cGMP concentrations increased significantly during (1.7-fold) and after (1.9-fold) L-Arg infusion, but only slightly (1.3-fold) during saline infusion. 4. Urine flow increased more remarkably following L-Arg infusion than that following saline infusion. Remarkable increases in urinary excretion of sodium and fractional excretion of sodium were observed after L-Arg infusion compared with those after saline infusion. Natriuresis was associated with enhanced urinary excretion of cGMP and Nox. Urinary Nox excretion showed positive correlations with urinary flow (r = 0.69, P less than 0.001) and with urinary cGMP excretion (r = 0.60, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Outbreaks of acute gastroenteritis caused by small round structured viruses in Tokyo].

Of 34 non-bacterial gastroenteritis outbreaks which occurred at day-care centers, kindergartens, elementary and secondary schools in Tokyo during the period from February 1985 to June 1991, 28 outbreaks from which small round structured viruses (SRSV) were detected in the patients' stool specimens by electron microscopy were subjected to an epidemiological investigation. The outbreaks tended to occur frequently in the cold season; twenty-two (79%) of these outbreaks from November through April. Though detailed epidemiological informations was not obtained from all outbreaks, the common source of infection were presumed to be present in many of the outbreaks, judged from the incidence as to time course of patients. Food doubted to be incriminated as transmission vehicles in these outbreaks was served at schools, kindergartens, and lodgings. In some outbreaks, SRSV was detected from stool specimens of food handlers, or they were seroconverted to SRSV, suggesting that food was incriminated as a transmission vehicle. The symptoms of patients differ slightly from age to age: in the age range of 0 to 6 years, vomiting 90%, fever 41% and diarrhea 32%; in the 6 to 12 year-olds, nausea 61%, vomiting 48%, abdominal pain 65%, diarrhea 20% and fever 29%; and in the 12 to 15 year-olds, nausea 69%, vomiting 42%, abdominal pain 60%, diarrhea 30% and fever 34%. The lower the age of patient vomiting was more frequently observed. In these lower age groups, the frequency of nausea and vomiting tended to exceed that of diarrhea.

Adolescent↗

Defective production of interleukin-6 in very small premature infants in response to bacterial pathogens.

In the present study, a whole-blood culture was employed to examine the ability of preterm and term newborn infants to produce interleukin-6 (IL-6) in response to major bacterial pathogens such as group B streptococci, Escherichia coli, Listeria monocytogenes, and Streptococcus pneumoniae. Similarly, in response to stimulation with lipopolysaccharide, a potent stimulant for monocyte cytokine production, appreciable levels of IL-6 activity in the stimulated whole blood from term newborns as well as adults was effectively induced by all of these pathogens. In contrast to that of term infants, the bacteria-induced IL-6 production of preterm infants, especially those born before 30 weeks of gestation, was somewhat decreased (P less than 0.01 for each pathogen). It was also demonstrated that IL-6 responses to lipopolysaccharide stimulation were reduced in preterm newborns (for term versus preterm newborns less than 30 weeks of gestation, P was less than 0.01). These findings imply some inherent abnormality of monocytes in preterm babies. The diminished IL-6 production may be partly responsible for the susceptibility of preterm newborn infants to bacterial infections.

Adult↗

Porphyromonas gingivalis fimbriae induce expression of the neutrophil chemotactic factor KC gene of mouse peritoneal macrophages: role of protein kinase C.

To account for infiltration of the periodontal tissues by neutrophils, the present study was undertaken to examine whether Porphyromonas gingivalis fimbriae, important structures involved in attachment of the bacteria to periodontal tissues, induce gene expression of the neutrophil chemoattractant KC in macrophages. The fimbriae induced expression of the KC gene of mouse peritoneal macrophages in a dose-dependent fashion. The peak of KC gene expression was observed as early as 1 h after initiation of the treatment. However, the gene expression was short lived, with the expression decreasing gradually after 6 h. A nuclear transcriptional assay showed that the fimbriae regulated the KC gene expression at a posttranscriptional level. We observed that the fimbria-induced KC gene expression was not regulated by endogenous or exogenous prostaglandin. Furthermore, forskolin, a potent activator of adenyl cyclase, and dibutyryl cyclic AMP were incapable of inducing KC gene expression of the peritoneal macrophages. H-8 and HA 1004, inhibitors of cyclic nucleotide-dependent protein kinases, had little effect on the fimbria-induced KC gene expression. On the other hand, the fimbria-induced KC gene expression was inhibited markedly by treatment with H-7, a potent inhibitor of protein kinase C. We also observed that phorbol 12-myristate 13-acetate, a specific activator of protein kinase C, induced KC gene expression of peritoneal macrophages in a dose-dependent fashion. In addition, the fimbria-induced KC gene expression was suppressed in the peritoneal macrophages pretreated for 24 h with phorbol 12-myristate 13-acetate. These results suggest that the KC gene expression was mediated through activation of protein kinase C and not through that of cyclic nucleotide-dependent protein kinases. The present study indicates that P. gingivalis fimbriae can induce gene expression of the neutrophil chemotactic factor KC by macrophages via protein kinase C and suggests that this factor may be involved in infiltration of neutrophils into the periodontal tissues of adult periodontal patients.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Aberrant cytokine production from tenosynovium in dialysis associated amyloidosis.

Culture supernatants of tenosynovial tissues from patients with carpal tunnel syndrome undergoing chronic haemodialysis contained interleukin (IL) 1-like and IL6-like activity. These culture supernatants also induced active proliferation of rheumatoid synovial cells. Immunohistochemical analysis of teno-synovial tissues showed the accumulation of mononuclear cells bearing CD14 and HLA-DR antigens adjacent to the deposition of amyloid protein (beta 2 microglobulin). These cells also reacted with antibodies to IL1 and IL6 respectively. These data suggest that multiple cytokines, including IL1 and IL6, produced from tenosynovial tissues in patients with dialysis associated amyloidosis might induce the proliferation of synovial cells that, together with deposition of amyloid protein, might cause carpal tunnel syndrome.

Aged↗

Animal species differences in erythrocyte aggregability.

Species differences in erythrocyte aggregability were investigated employing our whole blood erythrocyte aggregometer. Blood was sampled from seven species, including humans and anesthetized (30 mg/kg pentobarbital) animals. The erythrocyte aggregation rates were the following (in s-1): cats, 0.213 +/- 0.027 (means +/- SD); dogs, 0.164 +/- 0.027; men, 0.112 +/- 0.025; rats, 0.111 +/- 0.005; domestic rabbits, 0.049 +/- 0.021; and mongolian gerbils, 0.034 +/- 0.015. Domestic fowls did not exhibit erythrocyte aggregograms like those seen in the other species. Statistical analysis revealed significant differences among the erythrocyte aggregation rates of the different species (multiple-comparisons with an overall significance level of 0.05) except between men and rats and between rabbits and gerbils. No single factor which is known to accelerate the erythrocyte aggregation rate (hematocrit, fibrinogen, etc.) was correlated with the erythrocyte aggregation rate except the globulin concentration in the blood. The failure to detect erythrocyte aggregation in domestic fowls was probably attributable to their erythrocyte shape. These results suggest that each species has its own proper tendency for erythrocyte aggregation. This factor must be taken into consideration when the blood circulation is discussed among different animal species.

Animals↗

Effects of endothelin on renal hemodynamics and tubuloglomerular feedback.

The effect of endothelin (ET)-1 infusion on renal hemodynamics and the tubuloglomerular feedback (TGF) mechanism was examined in rats. ET-1 reduced early proximal flow rate (EPFR) measured in the absence of distal flow from 28 +/- 1 to 23 +/- 1 nl/min at a subpressor dose (100 pmol.100 g body wt-1.h-1 iv) and from 27 +/- 2 to 19 +/- 2 nl/min at a pressor dose (200 pmol.100 g body wt-1.h-1). Reductions of EPFR induced by loop perfusion at 40 nl/min were 11 +/- 1 and 12 +/- 1 nl/min at the subpressor and pressor doses and were not different from controls. The stop-flow pressure response to loop perfusion was not altered by the pressor dose of ET-1. The subpressor dose of ET-1 increased renal vascular resistance (RVR) by 40% but left glomerular filtration rate (GFR) and urinary excretion of sodium (UNaV) unaltered. The pressor dose of ET-1 not only increased RVR by 140% and decreased GFR and renal plasma flow by 37 and 52%, but it increased UNaV proportional to the rise in blood pressure (r = 0.724, P less than 0.01). ET-1 is a potent renal vasoconstrictor and induces pressure natriuresis. ET-1 increases both pre- and postglomerular resistances but does not affect TGF response.

Animals↗

Hemopoietic growth factors regulate the survival of human basophils in vitro.

Human basophils were purified from normal peripheral blood, using density gradient followed by negative panning selection. We tested the effects of hemopoietic growth factors on the survival of these basophils in vitro. In the absence of exogenous factors, basophils (purity greater than 90%) decreased in number rapidly. At day 7 only 11% of the cells remained alive in cultures; less than 1% of cells survived at day 14. Interleukin (IL)-3 maintained numbers of viable cells; cell viability was 67% at day 7 and 45% at day 14. Granulocyte-macrophage (GM)-colony-stimulating factor (CSF) exhibited slight effect on the survival; 33% of cells remained at day 7. Other growth factors including granulocyte (G)-CSF, macrophage (M)-CSF, and IL-4 had no significant effect on the survival of basophils at all. Morphological and functional characterization of cells maintained by IL-3 revealed that they belonged to the basophil lineage. These observations indicate that normal basophils possess functional receptors for IL-3 and GM-CSF and that both factors modulate immediate- and delayed-type hypersensitivity reactions by prolonging the life span of basophils.

Basophils↗

Idiopathic pulmonary fibrosis and high prevalence of serum antibodies to hepatitis C virus.

The prevalence of serum antibodies to hepatitis C virus (HCV) was assessed by an enzyme-linked immunosorbent assay (ELISA) in 66 patients (46 male and 20 female; mean age +/- SEM, 61.5 +/- 10.1 yr) with idiopathic pulmonary fibrosis (IPF). Nineteen (28.8%) were positive for this test. The frequency of HCV positiveness was significantly higher in the patients with IPF than in the 9,464 control subjects, whose ages were comparable with those of the patients (3.66%, p less than 0.05). Importantly, 12 of the 19 patients with IPF and positive ELISA results (63.2%) had positive results on the Chiron recombinant immunoblotting assay (RIBA), which is known to be more specific for HCV. We judged the 12 perceptible reactions as eight reactive and four indeterminate. When we examined liver function retrospectively, only two of eight patients who tested positive for the HCV had liver dysfunction, suggesting that anti-HCV positivity in IPF was not observed as a result of liver disease. These results lead us to speculate that HCV infection may play an important role in the pathogenesis of IPF, or that the sera of patients with IPF may contain some antibody against an unknown epitope and cross-react with the anti-HCV assay.

Aged↗

Hypersensitivity pneumonitis in athymic nude mice. Additional evidence of T cell dependency.

We previously demonstrated that C57 Black/6 mice develop lung lesions similar to human hypersensitivity pneumonitis (HP) by repeated transnasal administration of Thermoactinomyces vulgaris (Tv) antigen. To elucidate the role of T cells in the development of this disease, Tv antigen (90 micrograms/day) was transnasally administered to athymic nude C57 Black/nu/nu (nu) mice and their littermates (+/nu) three times a week for 3 wk. The nude mice developed minimal lung lesions, whereas their thymus-intact littermates (+/nu) showed changes equivalent to those in C57 Black/6. Changes in local inflammatory cell responses were evaluated by bronchoalveolar lavage, and increases in the numbers of lymphocytes and macrophages were significantly less severe in the nude mice than in the +/nu mice. Interestingly, the increase in polymorphonuclear leukocytes 6 h after the last antigen inoculation was equivalently seen in both groups. When spleen-derived T cells (more than 95% Thy-1.2+) from the sensitized +/nu mice were adoptively transferred to nude mice, the HP-like lesions in the recipients were found after Tv antigen challenge. These results suggest that Thy-1.2+ T cell-mediated immunity was necessary for the development of HP in this murine model.

Alveolitis, Extrinsic Allergic↗

Beta 2-adrenergic receptor mRNA is overexpressed in neoplastic human thyroid tissues.

The expression of beta 2-adrenergic receptor (AR) mRNA was investigated in normal and neoplastic human thyroid tissues. A combination of techniques for reverse transcribing mRNA into cDNA and the incorporation of 32P-gamma ATP into the polymerase chain reaction (PCR)-generated fragments allowed us to detect beta 2-AR mRNA in surgically excised thyroid specimens. The levels of beta 2-AR cDNA generated by PCR in thyroid adenomas and cancers were 3.3 and 6.9 times, respectively, as high as that of normal thyroid tissues. These findings suggest that the level of beta 2-AR mRNA is correlated with the extent of differentiation in neoplastic tissues. The present study provides new insights into the relationships between the AR-adenylate cyclase system and the regulation of the growth and differentiation in neoplastic human thyroid tissues.

Base Sequence↗