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Biomedical subjects

K Ogino

Publications and source records attributed to K Ogino.

At least 73 records · Page 4Linked to original sources

Opioid peptides mediate heat stress-induced immunosuppression during pregnancy.

To clarify the involvement of the opioid system in enhanced immunosuppression induced by heat stress during pregnancy, we examined the effects of heat exposure and intraperitoneal administration of opioid receptor antagonist naloxone on beta-endorphin (beta-EP) in blood, pituitary lobes, and placenta as well as splenic natural killer cell activity (NKCA) and placental steroids in pregnant rats at 15-16 days gestation. Two-way analysis of variance revealed significant increases in blood beta-EP induced by heat and naloxone and a significant interaction between heat and naloxone on blood beta-EP and progesterone (P). Whereas heat reduced NKCA, intraperitoneal administration of naloxone reversed it. Significant increases in blood and placental beta-EP induced by both heat and naloxone administration and a significant interaction on blood and placental beta-EP was observed. These results suggest that immunosuppression produced by heat stress during pregnancy is mediated by the opioid system. A positive correlation between beta-EP in blood and placenta during heat and naloxone administration suggests that increased placental beta-EP during heat results in hypersecretion of beta-EP into blood. P increased by heat during pregnancy may be involved in the immunosuppression.

Animals↗

Sympathetic nervous response relative to the adenosine triphosphate supply-demand imbalance during exercise is augmented in patients with heart failure.

OBJECTIVE: Increase in plasma hypoxanthine (HX) (purine nucleotide degradation product from working muscle) reflects insufficiency of adenosine triphosphate (ATP) supply during exercise, and the exercise-induced increase in plasma norepinephrine (NE) can be an index of sympathetic nerve activity. The aim of this study was to investigate the relationship between plasma NE and plasma HX during exercise in patients with heart failure (HF) according to its severity. METHODS: Blood lactate, plasma HX, and plasma NE were measured at rest and after symptom-limited cardiopulmonary exercise test in 54 patients with HF (New York Heart Association [NYHA] classes I:18, II:20, III:16) and 19 normal subjects. RESULTS: Peak work rate and peak oxygen uptake decreased as the NYHA functional class increased. Blood lactate and plasma HX levels at rest were comparable, but peak blood lactate (normal, NYHA I, II, III: 6.4+/-0.3, 5.6+/-0.4, 5.3+/-0.3, 3.5+/-0.2 mmol/L) and peak plasma HX (3.6+/-0.4, 3.0+/-0.5, 2.4+/-0.3, 1.4+/-0.1 micromol/L) were progressively smaller as HF worsened. Resting plasma NE (137+/-15, 180+/-29, 201+/-21, 318+/-55 pg/mL) was significantly higher in NYHA class III HF, but peak plasma NE (2,235+/-356, 2,021+/-326, 2,188+/-292, 2,210+/-316 pg/mL) was not different among groups. The ratio of the exercise increments in plasma NE to the increments in plasma HX during exercise (deltaplasma NE/deltaplasma HX: 666+/-96, 1,083+/-229, 1,252+/-222, 2,260+/-351) increased according to the severity of HF. CONCLUSION: These data suggest that plasma levels of HX after maximal exercise are smaller as HF worsened, and sympathetic responsiveness to the imbalance of ATP supply-demand during exercise is augmented according to the severity of HF.

Adenosine Diphosphate↗

Effects of excess K+ on carbachol-induced contractions in the guinea-pig tracheal muscle.

1. In smooth muscles isolated from the guinea-pig trachea, the effects of dihydropyridines, nifedipine and nicardipine on contractions produced by carbachol (Cch) were studied in normal (6 mM) and excess K+ concentration (60 mM). The tonic contraction produced by 1 microM Cch was highly dependent on the external Ca2+ concentration ([Ca2+]0) and was not significantly affected by cyclopiazonic acid or thapsigargin, Ca2+ uptake inhibitor. 2. [Ca2+]0-tension curves were steeper in the presence of 1 microM Cch (the Hill coefficient: 2.5) than in the presence of 60 mM K+ (Hill coefficient: 1.6) and their ED50 of Ca2+ was 0.16 and 0.39 mM, respectively. An increase of K+ to 60 mM in the presence of 1 microM Cch shifted the curve to the left roughly in parallel (ED50: 0.12 mM, Hill coefficient: 2.3). 3. [Ca2+]0-tension curve in the presence of 1 microM Cch was shifted to the right in parallel by nifedipine (1 microM). This was markedly potentiated by 60 mM K+ (the increase in ED50 of Ca2+ being 3 times at 6 mM and 15 times at 60 mM K+). No tension was evoked by Ca2+ up to 2.5 mM in 60 mM K+ solution containing 1 microM nifedipine but no Cch. 4. In the absence of nifedipine, Cch-induced contractions were potentiated by 60 mM K+, whereas in the presence of nifedipine, Cch-induced contractions were markedly inhibited by 60 mM K+. These mechanical changes were accompanied by an increase or a decrease in intracellular Ca2+. 5. A hypothesis is presented to explain the results which suggests that the kinetics of Ca2+ influx though a single type of pathway is modulated by membrane potential and receptor activation and that the susceptibility of the pathway to dihydropyridine blockade is closely related to the Ca2+ influx kinetics with receptor activation reducing and membrane depolarization increasing the susceptibility.

Animals↗

The effects of nickel and cobalt ions on the spontaneous electrical activity, slow wave, in the circular muscle of the guinea-pig gastric antrum.

1. Circular muscle strips of the guinea-pig gastric muscle produced spontaneous electrical activity in the form of slow waves. The slow wave amplitude, maximum rate of rise, duration, and frequency were 31 mV, 60 mV sec-1, 4.3 sec, and 4.3 min-1 on average, respectively. These parameters were not appreciably affected by 3 microM nifedipine or nicardipine, even following membrane depolarization with 60 mM K+. 2. Ni2+ (1-100 microM) increased slow wave amplitude and frequency, but reduced the rate of rise, accompanied by membrane depolarization. The rate of rise and depolarization slowly recovered to the control values in the continuous presence of Ni2+, but slow wave frequency remained high. The recovery after wash-out was very poor particularly when a high concentration of Ni2+ was applied. 3. The effects of Co2+ were fundamentally the same as those of Ni2+. 4. Removal of external Ca2+ slowly reduced the rate of rise and amplitude of the slow waves in the absence and the presence of Ni2+ and Co2+, although the effects were reduced in the presence of these metal ions. 5. Concentrations of Ni2+ and Co2+ greater than 1 mM suppressed the slow waves. However, when the external Na+ was replaced with N-methyl-D-glucamine during the suppression, nearly normal electrical activity was resumed. 6. Since slow waves were not significantly affected by nifedipine (3 microM) and Ni2+ (100 microM), the inward currents generating slow waves do not seem to flow through L-type Ca2+ channels or typical T-type Ca2+ channels. Slow waves are probably potentiated by Ni2+ and Co2+ acting intracellularly. These ions at higher concentrations seem to inhibit the pacemaker activity more powerfully than they do the inward currents responsible for slow wave generation.

Animals↗

Hematuria in patients with renal hypouricemia.

The characteristics of urate metabolism in renal hypouricemic patients with hematuria were studied to clarify the risk factors for hematuria in patients with renal hypouricemia. In 16 Japanese patients with isolated renal hypouricemia, urate metabolism was measured using the urate clearance study and the subtype of renal hypouricemia [defective presecretory reabsorption (Pre), defective postsecretory reabsorption (Post), enhanced tubular secretion (Secretion) and defective presecretory and postsecretory reabsorption (Pre&Post)] were determined by the pharmacological tests. Hematuria was seen in 7 out of the 16 patients (44%), all of whom were females (58%). Serum urate and urinary urate concentrations were significantly higher in the group with hematuria (Sur = 1.76 +/- 0.31 mg/dl and Uur/Ucr = 0.75 +/- 0.12: p<0.05) than in the group without hematuria (Sur = 1.44 +/- 0.46 mg/dl and Uur/Ucr = 0.56 +/- 0.04), although there was no difference in the urate excretion rate between the two groups. Hematuria was more likely to be accompanied by Post (75%) and Secretion (75%), which showed significantly higher urinary urate concentration (Uur/Ucr = 0.75 +/- 0.1 and 0.69 +/- 0.13, respectively) than by Pre (25%) and Pre&Post (0%), which showed lower urinary urate concentration (0.61 +/- 0.06 and 0.62 +/- 0.05, respectively). The risk factors for hematuria in patients with renal hypouricemia are the elevation of urinary urate concentration and the subtypes of Post and Secretion.

Adult↗

Excess urate excretion correlates with severely acidic urine in patients with renal hypouricemia.

We evaluated the renal handling of urate in 12 Japanese renal hypouricemia patients, and studied the relationship between the renal handling of urate and the urinary pH. The patients were classified into the 4 subtypes of renal hypouricemia: (defective presecretory reabsorption (Pre), defective postsecretory reabsorption (Post), enhanced tubular secretion (Secretion), and defective presecretory and postsecretory reabsorption (Pre&Post) as based on a pharmacological test. Seven patients showed acid urine with a urinary pH of less than 5.9, although this was not accompanied by any abnormality of blood pH, partial pressure of carbon dioxide (PaCO2), or blood HCO3-. The urinary pH in the morning significantly correlated with the ratio of urate clearance to creatinine clearance in the morning, whereas the urinary urate concentration in the morning did not correlate with the urinary pH in the morning. In the Pre&Post patients, the urate excretion was higher and the urinary pH was more acidic compared to the other subtypes. The administration of K+-, Na+-citrate significantly alkalized the urinary pH in the patients with renal hypouricemia. These results suggest that the acidic urine was significantly related to the Pre&Post subtype of renal hypouricemia with the higher urate excretion, and that this subtype might be a risk factor for complications in renal hypouricemia. The alkalization of urine might be a useful treatment for the complication of renal hypouricemia.

Adult↗

Positive chronotropic actions of parathyroid hormone and parathyroid hormone-related peptide are associated with increases in the current, I(f), and the slope of the pacemaker potential.

BACKGROUND: The classic calciotropic hormone parathyroid hormone (PTH) and its paracrine factor parathyroid hormone-related protein (PTHrP) both increase heart rate. METHODS AND RESULTS: We used standard electrophysiological techniques to study the effects of PTH and PTHrP on isolated rabbit sinus node, isolated canine Purkinje fibers, and disaggregated rabbit sinus node myocytes. Sinus node maximum diastolic potential, activation voltage, and amplitude were unchanged by PTH or PTHrP (P>.05). However, the slope of phase 4 and the automatic rate were increased at PTH and PTHrP > or = 10 nmol/L (P<.05). Comparable results were seen in canine Purkinje fibers. We then used the perforated-patch technique to study the I(f) pacemaker current in sinus node. PTH 12.5 nmol/L and PTHrP 12.5 to 18 nmol/L increased I(f) at -65 mV by 68+/-41% (n=5) and 69+/-50% (n=5), respectively. Actions of both agents were reversible. The increase in I(f) appeared to result from a change in maximal conductance and not a shift in the voltage dependence of activation. CONCLUSIONS: These observations provide, for the first time, direct electrophysiological support for the chronotropic actions of PTH and PTHrP. They suggest that classic hormones and paracrine factors can have multiple functions and that in the case of PTH and PTHrP, a newly recognized action is to alter automaticity directly.

Action Potentials↗

Amyloid beta-protein (Abeta) 1-40 but not Abeta1-42 contributes to the experimental formation of Alzheimer disease amyloid fibrils in rat brain.

Two major C-terminal variants ending at Val40 and Ala42 constitute the majority of amyloid beta-protein (Abeta), which undergoes postsecretory aggregation and deposition in the Alzheimer disease (AD) brain. To probe the differential pathobiology of the two Abeta variants, we used an in vivo paradigm in which freshly solubilized Abeta1-40 or Abeta1-42 was injected into rat brains, followed by examination using Congo red birefringence, Abeta immunohistochemistry, and electron microscopy. In the rat brain, soluble Abeta 1-40 and Abeta1-42 formed aggregates, and the Abeta1-40 but not the Abeta1-42 aggregates showed Congo red birefringence. Electron microscopy revealed that the Abeta1-40 aggregates contained fibrillar structures similar to the amyloid fibrils of AD, whereas the Abeta1-42 aggregates contained nonfibrillar amorphous material. Preincubation of Abeta1-42 solution in vitro led to the formation of birefringent aggregates, and after injection of the preincubated Abeta1-42, the aggregates remained birefringent in the rat brain. Thus, a factor or factors might exist in the rat brain that inhibit the fibrillar assembly of soluble Abeta1-42. To analyze the postsecretory processing of Abeta, we used the same in vivo paradigm and showed that Abeta1-40 and Abeta1-42 were processed at their N termini to yield variants starting at pyroglutamate, and at their C termini to yield variants ending at Val40 and at Val39. Thus the normal rat brain could produce enzymes that mediate the conversion of Abeta 1-40/1-42 into processed variants similar to those in AD. This experimental paradigm may facilitate efforts to elucidate mechanisms of Abeta deposition evolving into amyloid plaques in AD.

Alzheimer Disease↗

Involvement of central neurotensin in thermoregulatory and neuroimmune function in pregnant rats exposed to heat.

To examine a functional relationship among pregnancy and central neurotensin and thermoregulatory and neuroimmune systems during heat stress, we monitored colonic temperature in six virgin female rats and six pregnant rats (9 to 11 days gestation) exposed to a microwave source. We also assayed splenic natural killer cell activity (NKCA), blood corticosterone (CS), and ACTH as indicators of the hypothalamic-pituitary-adrenal axis, beta-endorphin (beta-EP), and neurotensin (NT) in discrete brain regions. Additionally, we clarified the effects of intracerebroventricular (icv) administration of NT antiserum on these same responses in pregnant rats exposed to heat stress. Repeated-measures analysis of variance showed significant main effects of heat and pregnancy and a significant interactive effect on colonic temperature. Significant elevation in blood CS, ACTH, beta-EP, and NT in the hypothalamus and significant reductions in splenic NKCA and NT in the nucleus accumbens were produced by heat. In the experiment examining the effect of icv administration of NT antiserum, significant main effects of heat and administration and a significant interactive effect on colonic temperature were observed. Icv administration of NT antiserum increased splenic NKCA and decreased blood beta-EP. These results show that pregnancy enhances thermal homeostasis, suggesting central thermoregulatory mechanisms through NT in nucleus accumbens and hypothalamus in which placental or pituitary beta-EP may be involved. NT and beta-EP seem to play central roles simultaneously in heat-induced immunosuppression during pregnancy. Clarification for the effects of NT antiserum on beta-EP in virgin rats or manipulation of agents related to opioid system should be the focus of future work.

Adrenocorticotropic Hormone↗

Inhibitory effect of pregnancy on stress-induced immunosuppression through corticotropin releasing hormone (CRH) and dopaminergic systems.

To clarify the involvement of pregnancy in the response of the neuroendocrine-immune system to stress, we examined splenic natural killer-cell-activity-(NKCA) and its relevant central and blood parameters in female virgin and pregnant rats (10 to 11 days gestation) exposed to forced water-immersion stress with durations of 90 min and 180 min. Decreases in splenic NKCA, corticotropin releasing hormone (CRH) in the hypothalamus, and increases in progesterone (P), beta-endorphin (beta EP), and dopamine (DA) metabolic ratios in the frontal cortex and nucleus accumbens produced by stress were recognized in the virgin rats, but not in the pregnant rats. Pregnancy reduced splenic NKCA in rats without stress, but elevated it in the rats exposed to stress with a duration of 180 min. These findings suggest inhibitory effects of pregnancy on stress-induced immunosuppression and neuroendocrine changes, thereby promoting homeostasis in the neuroendocrine-immune system against stress. Such enhanced homeostasis associated with pregnancy seemed to be mediated by the activation of placental P and placental or pituitary beta EP in cooperation with mesocortical and mesolimbic DA systems and hypothalamic CRH.

Animals↗

Responses of catecholamines, renin-angiotensin system, and atrial natriuretic peptide to exercise in untrained men and women.

1. Plasma norepinephrine (NE), epinephrine (E), renin activity (PRA), angiotensin II (ATII), aldosterone (ALD), and atrial natriuretic peptide (ANP) were measured in 20 male and 15 female subjects during submaximal treadmill test. 2. Exercise duration was not different between the two groups (male vs. female: 13.4 +/- 0.8 min vs. 11.6 +/- 0.7 min, ns). Female subjects had higher heart rate during exercise, while systolic blood pressure at peak exercise was higher in male subjects. 3. Plasma NE, E, ANP, and ATII responses were comparable between male and female subjects, but PRA both at rest and during exercise and ALD at rest were significantly higher in male subjects. 4. Cardiac responses to submaximal exercise were different between male and female subjects, but neurohormonal responses were comparable between the two groups except for the high PRA at rest and during exercise and high plasma ALD at rest in male subjects.

Adult↗

Influence of extracellular H+ and Ca2+ on Ro 22-9194-induced block of sodium current in cardiac myocytes.

1. Ro 22-9194 reduced the Na current in ventricular myocytes in either a tonic block or phasic block manner. 2. Ro 22-9194 had a higher affinity to the inactivated state (Kdi = 10.3 microM) than to the rested state (Kdrest = 180 microM). 3. Extracellular acidification enhanced the tonic block but reduced the phasic block. 4. Elevation of extracellular Ca2+ inhibited the enhancing effects of extracellular acidification. 5. These findings suggest that Ro 22-9194 strongly inhibits Na+ channels of the ventricular myocytes of the diseased hearts, characterized by the depolarized cell membranes and by acid conditions.

Animals↗

Histopathological changes induced by zinc hydroxide in rat lungs.

Rat lungs were histologically examined at 1, 7, 14 and 28 days following a single intratracheal instillation of zinc hydroxide (1 mM). After one day of treatment, no confirmatory findings were noted. The zinc hydroxide injections were followed by an increase in proliferating cell nuclear antigen labeling indices in both alveolar macrophages and terminal bronchioles. After 7 days, the zinc hydroxide-treated lungs showed thickening of the interstitium with infiltration by alveolar macrophages, and an increase in the grade of Masson's trichrome staining (collagen fiber) in the alveolar interstitium. Thereafter, these morphological changes disappeared. The vehicle- and zinc sulfate (1 mM)-exposed lungs had no abnormalities at any time point. Formazan deposits in alveolar macrophages, formed as a result of nitro blue tetrazolium reduction, were increased in zinc hydroxide-treated lung slices, suggesting that zinc hydroxide stimulated super oxide anion generation from alveolar macrophages. These results show that zinc hydroxide can induce morphological alterations of rat lungs.

Animals↗

Clinical characteristics of patients with the initial diagnosis of NIDDM with positivity for antibodies to glutamic acid decarboxylase.

UNLABELLED: The measurement of islet cell antibodies (ICA) and antibodies to glutamic acid decarboxylase (GAD-Ab) is clinically useful in evaluating patients with insulin-dependent diabetes mellitus (IDDM). Our objective was to correlate the clinical characteristics of patients with non-insulin-dependent diabetes mellitus (NIDDM) who exhibited positivity for GAD-Ab vs. patients who were negative for this enzyme. The serum level of GAD-Ab was measured by radiobinding assay (RBA) using pig brain GAD. The prevalence of GAD-Ab in the 181 patients was low; the 8 involved subjects (4.4%) were all females. The NIDDM patients who were GAD-Ab-positive were significantly younger, experienced diabetes onset at an early age, had a shorter duration of diabetes, a shorter interval between diabetes onset to initiation of insulin therapy, a lower body mass index (BMI), a lower serum C-peptide value, and required a higher dose of insulin. A higher proportion of the GAD-Ab-positive patients was receiving insulin therapy. CONCLUSIONS: Clinical characteristics of patients with NIDDM who were positive for GAD-Ab differed significantly from those of the patients negative for GAD-Ab. The profile of the GAD-Ab-positive patients with NIDDM resembled that of those with IDDM.

Adult↗

Alpha-fetoprotein (AFP) levels in normal children.

Alpha-fetoprotein (AFP) is an important tumor marker for yolk sac tumor and hepatoblastoma in childhood. We have been using the graph of the normal range of serum AFP made by Tsuchida et al, when we evaluate the serum AFP levels in early infancy. We measured the serum AFP levels by an immunoradiometric assay in 163 normal infants under 2 years of age, in order to make a more precise graph. Our normal range was a little wider than that of Tsuchida et al. According to our graph, false-positive cases would be fewer. Referring to the half-lives of serum AFP levels in normal infancy is also useful, when it is difficult to evaluate the AFP level.

Age Factors↗

Tonic block of the Na+ current in single atrial and ventricular guinea-pig myocytes, by a new antiarrhythmic drug, Ro 22-9194.

Ro 22-9194 reduced the Na+ current in the atrial myocytes as well as ventricular myocytes in a tonic block fashion. Ro 22-9194 had a higher affinity to the inactivated state Na+ channels (KdI = 3.3 microM in atrial myocytes, KdI = 10.3 microM in ventricular myocytes) than to those in the rested state (KdR = 91 microM in atrial myocytes, KdR = 180 microM in ventricular myocytes), which indicated that Ro 22-9194 had a higher affinity to the Na+ channels in atrial myocytes than in ventricular myocytes. Ro 22-9194 shifted the inactivation curve in the hyperpolarized direction in both atrial and ventricular myocytes. These findings suggest that Ro 22-9194 more strongly inhibited the Na+ channel of the atrial myocytes of the diseased hearts with the depolarized membranes potentials than the Na+ channels in ventricular myocytes.

Animals↗

Effects of exposure to microwaves on cellular immunity and placental steroids in pregnant rats.

OBJECTIVES: Microwaves produce various detrimental changes based on actions of heat or non-specific stress, although the effects of microwaves on pregnant organisms has not been uniform. This study was designed to clarify the effect of exposure to microwaves during pregnancy on endocrine and immune functions. METHODS: Natural killer cell activity and natural killer cell subsets in the spleen were measured, as well as some endocrine indicators in blood--corticosterone and adrenocorticotrophic hormone (ACTH) as indices of the hypothalamic-pituitary-adrenal axis--beta-endorphin, oestradiol, and progesterone in six female virgin rats and six pregnant rats (nine to 11 days gestation) exposed to microwaves at 10 mW/cm2 incident power density at 2450 MHz for 90 minutes. The same measurements were performed in control rats (six virgin and six pregnant rats). RESULTS: Skin temperature in virgin and pregnant rats increased immediately after exposure to microwaves. Although splenic activity of natural killer cells and any of the subset populations identified by the monoclonal antibodies CD16 and CD57 did not differ in virgin rats with or without exposure to microwaves, pregnant rats exposed to microwaves showed a significant reduction of splenic activity of natural killer cells and CD16+CD57-. Although corticosterone and ACTH increased, and oestradiol decreased in exposed virgin and pregnant rats, microwaves produced significant increases in beta-endorphin and progesterone only in pregnant rats. CONCLUSIONS: Microwaves at the power of 10 mW/cm2 produced activation of the hypothalamic-pituitary-adrenal axis and increased oestradiol in both virgin and pregnant rats, suggesting that microwaves greatly stress pregnant organisms. These findings in pregnant rats suggest that--with exposure to microwaves--pregnancy induces immunosuppression, which could result in successful maintainance of pregnancy. This enhancement of adaptability to heat stress with pregnancy may be mediated by activation of placental progesterone and placental or pituitary beta-endorphin.

Adrenocorticotropic Hormone↗