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Biomedical subjects

Y Ohta

Publications and source records attributed to Y Ohta.

At least 217 records · Page 12Linked to original sources
PubMed1999

The effect of alpha2-adrenergic drugs on the activity of neurons in the rat nucleus raphe magnus in vitro.

UNLABELLED: The nucleus raphe magnus (NRM) is an important descending inhibitory system for pain transmission. We tested whether clonidine, an alpha2-adrenergic agonist, and yohimbine, an alpha2-adrenergic antagonist, modulate the activity of NRM neurons using extracellular recording in a rat brainstem slice preparation. Clonidine 1-20 microM increased firing frequencies (FF) in 22 (37%) and decreased FF in 6 (10%) spontaneously active neurons. Correlation between the concentrations of clonidine and FF changes was unremarkable. Eight spontaneously active neurons (13%) showed increases followed by decreases in FF with increasing doses of clonidine. The remaining 24 neurons (40%) showed no change in FF. Yohimbine 1 microM decreased FF in 38 spontaneously active neurons (58%), whereas the remaining 27 neurons (42%) showed no change in FF. In some neurons, yohimbine antagonized the increase or decrease in FF by application of clonidine. In three silent neurons (25%), clonidine (5 or 10 microM) induced firing activity, which stopped or decreased with the increasing doses of clonidine. In the remaining nine neurons (75%), clonidine did not induce firing activity. We conclude that activation and inhibition of alpha2-adrenergic receptors of NRM neurons augments and suppresses output of the descending inhibitory pain pathway. IMPLICATIONS: The nucleus raphe magnus is implicated in descending control of the nociceptive processes. We found that clonidine and yohimbine increased and decreased, respectively, the firing activity of a substantial number of nucleus raphe magnus neurons. Clonidine and may facilitate and yohimbine may reduce the outflow of the descending inhibitory pathway.

Adrenergic alpha-Agonists↗
PubMed1999

Bleeding induced interleukin-6 decreases blood loss via activation of coagulation.

Hemorrhage is known to induce the production of inflammatory cytokines such as interleukin-6 (IL-6). IL-6 plays an intermediate role as a factor in the activation of coagulation cascade and exerts a lethal effect in sepsis. To examine the effect of endogenous IL-6 on blood loss, we performed four experiments in female ddY mice. Enzyme immunoassay using an uncontrolled hemorrhage model, i.e., 75% tail resection, revealed the production of serum IL-6 (Experiment 1). We also measured cumulative blood loss and survival rate (Experiment 2); measured blood pressure and performed thrombelastogram (TEG) (Experiment 3); and measured plasma thrombin-antithrombin III (TAT) complex levels in two groups, one pretreated with 1 mg of anti-IL-6 monoclonal antibody (mAb), and one with normal rat globulin (NRG) using the same model (Experiment 4). The mAb group showed a significantly higher blood loss than the NRG group. All mice survived for 5 days in both groups. Blood pressure did not differ between either group. The TEG results suggest that administration of anti-IL-6 mAb caused mild suppression of coagulation activation, but did not affect fibrinolysis or platelets. In the mAb group, plasma TAT complex concentrations showed a significant decrease compared with the NRG group. In conclusion, hemorrhage-induced IL-6 may contribute to hemostasis through activation of coagulation, thus reducing blood loss.

Animals↗
PubMed1999

Characterization of infiltrating T cells in human scalp explants from alopecia areata to SCID nude mice: possible role of the disappearance of CD8+ T lymphocytes in the process of hair regrowth.

T cells may play a role in the pathogenesis of alopecia areata (AA). We attempted to elucidate the linkage between infiltrating T cells and hair regrowth processes by grafting scalp skin from the affected region of patients with AA onto severe combined immune deficiency (SCID) nude mice. When the AA scalp was grafted into the mice, the grafts were accepted, and normal hair regrowth was observed. Before grafting, CD4+ and CD8+ T cells had infiltrated into the peribulb area. After grafting, the telogen hair shifted to anagen hair, and the CD4+ and CD8+ T cell infiltrates in the bulb area decreased in all cases. CD8+ T cells had almost disappeared from all portions of the follicles. It has been suggested that CD8+ T cells play a crucial role in the pathogenesis of AA. The absence of CD8+ T lymphocytes that responded to follicular autoantigens may induce hair regrowth in the grafted skin. In addition, the CD4+ human T cells that had infiltrated or still remained in the upper-middle portions including the bulge area accompanied the HLA-DR expression after grafting. Infiltrating or surviving T cell phenotypes and locations changed during the hair cycle in the grafts. These results indicate that the location of infiltrated T cells and their phenotypes may participate not only in hair loss but also in regrowth of hair in AA.

Adult↗
PubMed1999

Lifetime prevalence of schizophrenia among individuals prenatally exposed to atomic bomb radiation in Nagasaki City.

OBJECTIVE: The aim of this study was to examine the relationship between prenatal exposure to atomic bomb (A-bomb) radiation and the development of schizophrenia in adulthood. METHOD: We investigated the lifetime prevalence of schizophrenia among people prenatally exposed to the 1945 Nagasaki A-bomb, using the schizophrenia register and the A-bomb survivors' database. RESULTS: Among 1867 prenatally exposed individuals, 18 subjects (0.96%) had developed schizophrenia later in life. The prevalence was significantly higher in people exposed in the second trimester of pregnancy than in those exposed in the third trimester. The closer they had been to the hypocentre, the higher was the prevalence, but no statistically significant linear relationship was seen. CONCLUSION: This investigation could not clarify the nature of exposure to A-bomb radiation as a risk factor for schizophrenia in the prenatal period.

Adult↗
PubMed1999

Insight into the primordial MHC from studies in ectothermic vertebrates.

MHC classical class I and class II genes have been identified in representative species from all major jawed vertebrate taxa, the oldest group being the cartilaginous fish, whereas no class I/II genes of any type have been detected in animals from older taxa. Among ectothermic vertebrate classes, studies of MHC architecture have been done in cartilaginous fish (sharks), bony fish (several teleost species), and amphibians (the frog Xenopus). The Xenopus MHC contains class I, class II, and class III genes, demonstrating that all of these genes were linked in the ancestor of the tetrapods, but the gene order is not the same as that in mouse/man. Studies of polyploid Xenopus suggest that MHC genes can be differentially silenced when multiple copies are present; i.e. MHC 'subregions' can be silenced. Surprisingly, in all teleosts examined to date class I and class II genes are not linked. Likewise, class III genes like the complement genes factor B (Bf) and C4 are scattered throughout the genome of teleosts. However, the presumed classical class I genes are closely linked to the 'immune' proteasome genes, LMP2 and LMP7, and to the peptide-transporter genes (TAP), implying that a true 'class I region' exists in this group. A similar type of linkage group is found in chickens and perhaps Xenopus, and thus it may reveal the ancestral organization of class I-associated genes. In cartilaginous fish, classical and non-classical class I genes have been isolated from three shark species, and class II A and B chain genes from nurse sharks. Studies of MHC linkage in sharks are being carried out to provide further understanding of the putative primordial organization of MHC Segregation studies in one shark family point to linkage of classical class I and class II genes, suggesting that the non-linkage of these genes in teleosts is a derived characteristic.

Animals↗
PubMed1999

Purification, characterization, and gene analysis of a chitosanase (ChoA) from Matsuebacter chitosanotabidus 3001.

The extracellular chitosanase (34,000 M(r)) produced by a novel gram-negative bacterium Matsuebacter chitosanotabidus 3001 was purified. The optimal pH of this chitosanase was 4.0, and the optimal temperature was between 30 and 40 degrees C. The purified chitosanase was most active on 90% deacetylated colloidal chitosan and glycol chitosan, both of which were hydrolyzed in an endosplitting manner, but this did not hydrolyze chitin, cellulose, or their derivatives. Among potential inhibitors, the purified chitosanase was only inhibited by Ag(+). Internal amino acid sequences of the purified chitosanase were obtained. A PCR fragment corresponding to one of these amino acid sequences was then used to screen a genomic library for the entire choA gene encoding chitosanase. Sequencing of the choA gene revealed an open reading frame encoding a 391-amino-acid protein. The N-terminal amino acid sequence had an excretion signal, but the sequence did not show any significant homology to other proteins, including known chitosanases. The 80-amino-acid excretion signal of ChoA fused to green fluorescent protein was functional in Escherichia coli. Taken together, these results suggest that we have identified a novel, previously unreported chitosanase.

Amino Acid Sequence↗
PubMed1999

Splenic contraction-induced reversible increase in hemoglobin concentration in intermittent hypoxia.

The effect of intermittent hypoxia (IHx) on blood hemoglobin concentration ([Hb]) and the underlying mechanisms were studied in rats exposed to 10% O2, 1 h/day, for up to 5 wk. IHx protocols with longer daily hypoxic exposure show persistent polycythemia; however, it is unknown whether [Hb] increases transiently during hypoxia in protocols without polycythemia. Hypoxia produced a reversible [Hb] increase after 4 days of IHx but not in normoxic controls (NxC) or after shorter period of IHx. Splenectomy abolished the phenomenon. Plasma epinephrine and norepinephrine levels during hypoxia were comparable in IHx and NxC groups, but the epinephrine-induced [Hb] increase was larger in IHx. The alpha1- and alpha2-adrenoreceptor blockade (phentolamine) and alpha2-blockade (yohimbine) abolished the [Hb] increase of IHx rats. Conversely, alpha2-receptor stimulation (oxymetazoline) increased [Hb] during normoxia in IHx but not in NxC. In conclusion, this IHx protocol results in reversible [Hb] increases during hypoxia via splenic contraction mediated by increased alpha2-adrenoreceptor response. This may protect O2 supply during hypoxia without the cardiovascular burden of polycythemia during normoxia.

Adrenergic alpha-1 Receptor Agonists↗
PubMed1999

Transfusion-associated graft-versus-host disease: an in situ hybridization analysis of the infiltrating donor-derived cells in the cutaneous lesion.

BACKGROUND: Acute graft-versus-host disease (GVHD) can occur after a blood transfusion. OBJECTIVE: In order to elucidate the pathomechanisms responsible for transfusion-associated GVHD, infiltrating donor-derived cells in a cutaneous lesion were analyzed. METHODS: A skin sample obtained from a 69-year-old woman who developed fatal GVHD after blood transfusions from male donors was studied by performing in situ hybridization (ISH) with a Y-chromosome-specific probe. RESULTS: The cell infiltrates comprised mainly CD3+ T lymphocytes. Immunohistochemistry and ISH in combination demonstrated that 99% (182/184) of the Y-body-positive cells were CD3+. Y bodies were observed in 80% of the CD8+ cells in the epidermis and dermoepidermal junction and in 77 and 45% of the CD8+ and CD4+ cells, respectively, in the dermis. CONCLUSION: These findings suggest that both CD4+ and CD8+ cells of donor origin were involved in the development of cutaneous GVHD.

Aged↗
PubMed1999

Cataract development in 12-month-old rats fed a 25% galactose diet and its relation to osmotic stress and oxidative damage.

We attempted to clarify the pattern of cataract development in 12-month-old rats fed a 25% galactose diet and to assess the relation of cataract development with osmotic stress and oxidative damage. In lenses of 12-month-old male Wistar rats fed a 25% galactose diet over an 8-month period, suture accentuation appeared at 6 months of galactose feeding and then opacities developed from the anterior subcapsular cortex toward the posterior subcapsular cortex, reaching the nuclear region at 8 months of galactose feeding. Increases in lens galactitol and lipid peroxide contents and a decrease in lens reduced glutathione content occurred at 4, 6 and 8 months of galactose feeding. The increase in lens lipid peroxide content and the decrease in lens reduced glutathione content were accelerated with an increase in feeding period, while the increase in lens galactitol content was decelerated. An increase in lens water content and a decrease in lens protein content occurred at 6 and 8 months of galactose feeding. The lens vitamin E content increased at 6 months of galactose feeding and this increase was concomitant with increases in serum vitamin E and total cholesterol concentrations. The serum lipid peroxide concentration increased at 4 and 6 months of galactose feeding. The present results indicate that in lenses of 12-month-old rats fed a 25% galactose diet, suture accentuation appears initially and then opacities develop from the anterior subcapsular cortex toward the posterior subcapsular cortex, finally reaching the nuclear region. These results also suggest that in the galactosemic aged rats, osmotic stress would mainly contribute to cataract formation, while oxidative damage could be linked to both cataract formation and progression, although an increase in lens vitamin E content occurs during the cataract development.

Animals↗
PubMed1999

Membrane active lipids in remnant lipoproteins cause impairment of endothelium-dependent vasorelaxation.

We have recently found that remnant lipoproteins (RLPs) and their lipid fractions impair endothelium-dependent vasorelaxation (EDR). This study was aimed at clarifying mechanisms responsible for RLP-induced endothelial dysfunction in isolated rabbit aortas. RLPs were isolated from plasma in hyperlipidemic subjects by use of the immunoaffinity gel mixture of anti-ApoA1 and anti-ApoB100 monoclonal antibodies and ultracentrifugation. Organ chamber experiments showed that EDR impairment was restored by addition of reduced glutathione (GSH) or N-acetylcysteine, antioxidants, into the incubation buffer containing isolated rabbit aortas and RLPs (0.75 mg of triglyceride/mL). Furthermore, the incubation of isolated human red blood cells (RBCs) with RLP and its lipids converted the normal shape of RBCs to echinocytes, but coincubation with antioxidants suppressed the RLP-induced RBC transformation, suggesting that they exerted oxidative damage on RBC surface membranes. Studies with HPLC and the postcolumn chemiluminescence method showed that RLPs contain a substantial amount of phosphatidylcholine hydroperoxides. Peroxidized phosphatidylcholine also impaired EDR and had echinocytogenic action, both of which were suppressed by N-acetylcysteine. RLPs isolated from the plasma of patients under treatment with alpha-tocopherol, an antioxidant, had a lower level of phosphatidylcholine hydroperoxides (15% of the amount in nontreated patients), which was associated with a lack of the inhibitory action on EDR and with lesser effect on RBC transformation. Oxidative damage caused by lipid components in RLPs, especially peroxidized phospholipids, deteriorates cell surface membrane and may be at least partly responsible for RLP-induced impairment of EDR.

Animals↗
PubMed1999

Alleviation of carbon tetrachloride-induced chronic liver injury and related dysfunction by L-tryptophan in rats.

We examined whether L-tryptophan (Trp) alleviates carbon tetrachloride (CCl4)-induced chronic liver injury and related dysfunction. Fifty rats were classified into four groups: the first (15 rats) served as the control; the second (10 rats) received subcutaneous injections of CCl4 (1.0 mL/kg) twice weekly for 8 weeks; the third (15 rats) received daily intraperitoneal injections of Trp (50 mg/kg) for 2 weeks after 6 weeks of CCl4 treatment; the fourth (10 rats) received both treatments. The activities of serum transaminases and the content of liver total hydroxyproline increased after 6 and 8 weeks of CCl4 treatment. The concentrations of serum albumin and liver protein and the in vitro activity of liver protein synthesis fell after 8 weeks of the treatment. Trp administration alleviated all these changes. At 6 and 8 weeks of CCl4 treatment the serum triglyceride concentration fell, whereas the liver triglyceride and lipid peroxide concentrations were elevated. Trp administration hardly affected these changes. These results indicate that Trp alleviates CCl4-induced chronic liver injury possibly by maintaining the activity of protein synthesis.

Animals↗
PubMed1999

A pharmacologic study on CO2 responsiveness of intracranial pressure in rats with chronic hypercapnia.

STUDY OBJECTIVES: To investigate intracranial pressure (ICP) changes and their mechanisms in chronic hypercapnia. DESIGN: After 12 male Wistar rats were maintained in CO2-mixed air (mean PaCO2, 71.0 mm Hg) for 21 weeks, their ICP levels were measured during the breathing of 0, 5, 10, 12, and 14% CO2-mixed air before and after the i.v. administration of nitro-L-arginine methyl ester (L-NAME). The ICP responses to i.v. norepinephrine and i.v. adenosine were also tested. Ten rats that were maintained in room air served as the control group. RESULTS: The mean ICP in the study group (5.9 mm Hg) was not significantly different from the mean ICP in the control group. In the study group, the ICP response to changes in PaCO2 was significantly blunted when compared to the response seen in the control group. In both groups, i.v. norepinephrine significantly increased the ICP. In the control group but not in the study group, i.v. L-NAME suppressed the ICP response to changes in PaCO2. In both groups, i.v. adenosine significantly increased the ICP. CONCLUSIONS: The ICP response to PaCO2 was blunted in rats with chronic hypercapnia, and the mechanism of this reduced response may involve nitric oxide.

Adenosine↗
PubMed1999

Screening school children for albuminuria, proteinuria and occult blood with dipsticks.

Beginning in 1974, the Japanese Ministry of Health Welfare directed the screening of schoolchildren for proteinuria. We studied their procedure and methods in 6197 school children and also evaluated a new urine dipstick that measures albumin concentrations down to about 10 mg/l and creatinine down to about 300 mg/l. We used specimens from adult in- and outpatients to test the accuracy of the dipsticks. Based on the quantitative results, we set as cutoffs < 150 mg/l for protein and < 30 mg/l for albumin as the concentrations representing "low risk." The quantitative values were assumed to be correct, and the dipstick results were judged accordingly, i.e., a dipstick protein of > or = "150" mg/l or an albumin of I "30" mg/l indicated increased risk of developing or having a genitourinary disorder. The sensitivity/specificity of the protein dipstick was 95.1%/95.5%, and the same for the albumin dipstick was 83.8%/93.8%. The cut-off for the albumin dipsticks probably should be set somewhat lower to reduce the number of false negatives and increase the sensitivity of the dipstick. When we compared the quantitative albumin to the protein dipsticks with the above cut-offs, we found the sensitivity/specificity to be 79.3%/94.4%, i.e., much like the albumin dipstick results. The many reports on the association of albuminuria and risk of renal disease recommend that screening should be done for albumin rather than protein. Based on the data from the school children, we estimate that a dipstick albumin of "30" mg/l is borderline increased risk, and that a protein dipstick of "150" mg/l is the same. If we call the dipstick "10" mg/l albumin, "30" mg/l albumin and the "150" mg/l protein results "low risk," then we estimate the prevalence of albuminuria in the school children to be about 2.1% and proteinuria to be about 4.3%. Children with these values should have a quantitative test for albumin and protein. We also tested a dipstick for creatinine and found increasing values with increasing age in both genders; the older boys had significantly higher creatinine values than the older girls and younger boys. For the albumin/creatinine ratio, we found 6028 children with a ratio of < 30 mg/g indicating low risk and 159 children with a ratio of > or = 30 mg/g indicating increased risk. The ratio may be more useful owing to the likely reduction of the number of false negatives and false positives.

Adolescent↗
PubMed1999

Shift in arm-pointing movements during gravity changes produced by aircraft parabolic flight.

It has been shown that target-pointing arm movements without visual feedback shift downward in space microgravity and upward in centrifuge hypergravity. Under gravity changes in aircraft parabolic flight, however, arm movements have been reported shifting upward in hypergravity as well, but a downward shift under microgravity is contradicted. In order to explain this discrepancy, we reexamined the pointing movements using an experimental design which was different from prior ones. Arm-pointing movements were measured by goniometry around the shoulder joint of subjects with and without eyes closed or with a weight in the hand, during hyper- and microgravity in parabolic flight. Subjects were fastened securely to the seat with the neck fixed and the elbow maintained in an extended position, and the eyes were kept closed for a period of time before each episode of parabolic flight. Under these new conditions, the arm consistently shifted downward during microgravity and mostly upward during hypergravity, as expected. We concluded that arm-pointing deviation induced by parabolic flight could be also be valid for studying the mechanism underlying disorientation under varying gravity conditions.

Adult↗
PubMed1999

Possible contribution of a decrease in serum albumin concentration to a low level of blood L-tryptophan in nephrotic rats.

In order to clarify whether or not a decrease in serum albumin concentration contributes to a low level of blood L-tryptophan (Trp) in nephrosis, blood Trp concentration at 30, 60, 90, and 120 min after oral administration of Trp (100 mumol/kg body weight) in the same rats injected once with puromycin aminonucleoside (PAN) (100 mg/kg body weight, i.p.), an inducer of nephrosis, was examined at different stages of nephrosis. The increase and decrease in blood Trp concentration after Trp administration were similar in the PAN-treated rats without nephrosis, the PAN-treated rats recovered from nephrosis, and untreated control rats. The maximum increase in blood Trp concentration at 30 min after Trp administration was lower in nephrotic rats than in control rats. In all rats treated with and without PAN, increased blood L-tryptophan concentrations at 30 min after L-tryptophan administration were positively correlated well with serum albumin concentrations (r = 0.88, p < 0.001). There was no difference in the intestinal absorption of the same dose of orally administered Trp between nephrotic and control rats. These results suggest that a decrease in serum albumin concentration may contribute to a low level of blood L-tryptophan in nephrosis.

Animals↗
PubMed1999

[Extended resection of the great vessels for primary lung cancer and mediastinal tumor].

From 1973 to 1998, we resected and reconstructed the great vessels in 44 patients with primary lung cancer or mediastinal tumor. Among them, 39 patients (28 with lung cancer and 11 with mediastinal tumor) and 5 patients (all with lung cancer) underwent reconstruction of the superior vena cava (SVC) and aorta, respectively. The SVC was repaired by expanded polytetrafluoroethylene (EPTFE) graft (n = 8), prosthetic patch (n = 5) or direct suture (n = 26). The aorta was repaired with temporary subclavian artery-descending aorta (n = 3), or left atrium-femoral artery bypass (n = 2). No complication or operative death occurred after surgery. The survival rate of the patients with lung cancer who underwent SVC reconstruction at 3 year and 5 year were 26.2% and 11.2%, respectively. Five of 11 (45.5%) patients with mediastinal tumor are alive at 5 years. We concluded that extended resection for primary lung cancer or mediastinal tumor invading the SVC is acceptable operation method for some patients.

Adult↗
PubMed1999

Epitope analysis of a prostate-specific antigen (PSA) C-terminal-specific monoclonal antibody and new aspects for the discrepancy between equimolar and skewed PSA assays.

BACKGROUND: Immunoassays to measure prostate-specific antigen (PSA) often give different values for the same patient samples, and the calibrators among commercial immunoassays are not interchangeable. We developed three novel assays to quantify the free and complexed forms of PSA in serum. METHODS: We synthesized 46 peptides, which encompassed the entire PSA molecule, and determined the interactions between selected monoclonal antibodies (MAbs) and those peptides or the intact PSA molecule. RESULTS: MAb PA313 did not cross-react with human glandular kallikrein (hK2), which has 78% amino acid homology to PSA. This MAb bound with KD = 40 nmol/L to the C-terminal peptide of PSA and distinguished between a synthetic peptide derived from PSA (PSA46A: NH2-C-R226KWIKDTIVANP237-COOH) that differed from one derived from hK2 (PSA46B: NH2-C-R226KWIKDTAANP237-COOH) by a single amino acid. Only the MAb combination of PA313/PA121 showed equimolar reactivity with PSA and with PSA complexed with alpha1-antichymotrypsin (PSA-ACT). The free form of PSA (F-PSA) was determined by MAbs PA313/FPA503, and the amount of complexed PSA (C-PSA) in PSA-ACT was determined by alphaACT/PA313. The total PSA (T-PSA) measured by either of the equimolar assays (PA313/PA121 or Tandem-R) was consistent with the sum of F-PSA and C-PSA. In contrast, T-PSA by a skewed assay (IMx) was higher than F-PSA + C-PSA when the ratio of F-PSA to T-PSA (F/T) was >0.15. T-PSA measured by IMx was nearly equal to F-PSA/0.55 + C-PSA. The coefficient 0.55 reflected different reactivities of the IMx assay with PSA-ACT and PSA. CONCLUSION: The discrepancy between the values measured by equimolar and skewed assays depends on the ratio of free to total PSA in the sample.

Amino Acid Sequence↗