Biomedical subjects

H Hiruma

Publications and source records attributed to H Hiruma.

33 records · Page 2Linked to original sources

PubMed1995

Sickle cell rheology is determined by polymer fraction--not cell morphology.

Sickle cell disease pathophysiology is mediated by acute and chronic impairment of cell flexibility due to the formation of intracellular sickle hemoglobin (Hb S) polymer as cells are partially deoxygenated in the microcirculation. We have recently developed a method to measure the relationship between the formation of intracellular polymerized Hb S and cell filtration. In this study, we have used this method to examine whether sickle cell morphology, independent of Hb S polymer fraction, had an effect on cell rheology. We primarily use sickle trait (AS) and Hb S-beta(+)-thalassemia (S-beta(+)-thal) erythrocytes with low hemoglobin F levels, which have normal membranes and few or no dense cells, to remove these confounding effects. We find that the relationship between filtration and the percentages of each "type" of morphological deformation of AS erythrocytes was different from that of the S-beta(+)-thal erythrocytes. In addition, we find that while the filtration of AS erythrocytes as a function of oxygen saturation was similar, whether measured during deoxygenation or reoxygenation, the relationship between the percentages of each type of deformed erythrocyte and oxygen saturation demonstrated hysteresis during oxygenation-deoxygenation experiments. Transmission electron microscopy, for both elongated and irregularly shaped cells, showed that similarly distorted cells could have very different amounts and alignment of polymer. These results suggests that cell morphology per se is not strongly related to filtration, whereas calculated intracellular Hb S polymer fraction predicts loss of filtration of AS and S-beta(+)-thal erythrocytes well. Measured or calculated polymer fraction values would appear to be a better parameter for the study of sickle cell disease pathophysiology and response to treatment than cell morphology studies.

Anemia, Sickle Cell↗

PubMed1995

Filterability of mixtures of sickle and normal erythrocytes.

We investigated the deformability of sickle (SS) cells from 25 patients and mixtures of these SS cells with blood type-compatible normal (AA) cells, using a nickel mesh filtration system, with the aim of determining optimal goals for exchange therapy. We found that for air-equilibrated SS/AA cell mixtures the fraction of dense cells (MCHC > 37 g/dl) is the determinant factor in filterability and that the dense cells contribute in a linear fashion to the loss of filtration up to 15% dense cells (y = -4.41x + 98.23, r = 0.945, P < 0.0001). The slope of this effect is approximately 25 times steeper than that of the relationship between filtration and percent nondense (MCHC < 37/g/dl) SS cells (y = -0.17x + 106.53, r = 0.772, P < 0.0001). A comparison of the proportion of high fluorescence reticulocytes to total reticulocytes (HFR ratio), indicating an elevation of immature reticulocytes, between six nontransfused patients and six exchange-transfused patients showed significant higher values in the nontransfused individuals (0.154 +/- 0.051 versus 0.070 +/- 0.054, P < 0.003). These results may have implications regarding targets for exchange transfusion therapy. Further studies of the effect on transfusion, both simple and exchange, on the numbers of dense cells and the proportions and populations of reticulocytes and the rheological characteristics of the erythrocyte subpopulations seems warranted.

Anemia, Sickle Cell↗

PubMed1995

Contributions of sickle hemoglobin polymer and sickle cell membranes to impaired filterability.

Sickle cell anemia is a disease of abnormal rheology caused by acute and reversible, as well as chronic and irreversible, changes in the properties and deformability of sickle erythrocytes. Deformability is determined by several factors, including intracellular sickle hemoglobin polymerization, the abnormal membrane properties of sickle cells, and the abnormal rheological properties of the soluble concentrated hemoglobin solution within dense sickle red blood cells. In this study, we used a 5-microns pore nickel mesh filter to evaluate quantitatively the effects of these factors on the filterability of erythrocytes containing sickle hemoglobin. We used sickle trait and sickle/beta(+)-thalassemia cells, because they have minimal membrane abnormalities or density heterogeneity, to investigate the effects of polymer formation on rheological properties. We found that filterability of these cells is sensitive to small amounts of intracellular polymer and that impaired filtration is linearly related to oxygen-dependent polymer formation, up to a polymer fraction of 0.3. By increasing the proportion of dense cells in populations of normal cells or cells from individuals with sickle syndromes and equilibrating these cells with gas ligands, we estimate that polymerization, even at 95% saturation, contributes twice as much to impaired filterability of sickle erythrocytes as the abnormal membranes in homozygous sickle cell disease. At lower saturation values, the effects of polymer are even greater. The viscosity of the concentrated hemoglobin in dense cells had the smallest effect, over physiologically relevant saturation values. These results emphasize the importance of sickle hemoglobin polymerization in the pathogenesis of sickle cell disease and should help define its pathophysiology and responses to therapy in quantitative terms.

Anemia, Sickle Cell↗

PubMed1995

Luteinizing hormone-releasing hormone is a putative factor that causes LHRH neurons to fire synchronously in ovariectomized rats.

Pulsatile release of luteinizing hormone (LH) is governed by pulsatile release of LH-releasing hormone (LHRH), and each LHRH pulse is produced by synchronized firing of LHRH neurons. However, the mechanism of this synchronized firing is unknown. An increase (volley) in the multiunit activity (MUA), at 20- to 30-min intervals, accompanied by an LH pulse, is found in the median eminence (ME) of ovariectomized rats, suggesting that the MUA reflects the activity of LHRH neurons directly or indirectly. On the hypothesis that LHRH released from LHRH neurons locally in the hypothalamus was involved in the mechanism responsible for the synchronized firings of LHRH neurons, we examined the effect of exogenously administered LHRH on the MUA showing volleys in association with pulsatile LH release in ovariectomized rats. Intravenous injection of LHRH (50 micrograms/kg) evoked a premature volley (average 5.0 min after the injection). Microinjection of LHRH (1 ng) into the ME also evoked a premature volley (average 4.6 min after the injection), accompanied by an LH pulse. Microinjection of LHRH (1 ng) into the medial preoptic area did not cause these effects. The results suggest that LHRH released from LHRH neurons locally in the hypothalamus somehow activates its own and neighboring LHRH neurons, causing synchronized firings of LHRH neurons, and that this mechanism exists at least in and around the ME.

Animals↗

PubMed1994

Injection of bicuculline elicits firing of luteinizing hormone releasing hormone pulse generator in muscimol-treated ovariectomized rats.

We have already demonstrated that, although exogenous gamma-aminobutyric acidA (GABAA) receptor agonist is capable of inhibiting the activity of luteinizing hormone releasing hormone (LHRH) pulse generator, the reduction in the endogenous GABAA receptor activity does not have a significant effect in ovariectomized rats, suggesting a minor role of inhibitory GABA neurons in the control of pulsatile release of LHRH. In this study, we further analyzed the role of the GABAA receptor system in the regulation of LHRH pulse generator activity observed by recording the multiunit activity (MUA) in the hypothalamus of ovariectomized rats. An abrupt increase (volley) in the MUA in the arcuate nucleus (ARC)-median eminence region (ME) was accompanied by the initiation of a luteinizing hormone (LH) pulse, determined by measuring LH concentrations in blood sampled simultaneously. The injection of 1-3 mg/kg muscimol (MUS), a GABAA receptor agonist, decreased the basal MUA and delayed the occurrence of the next MUA volley, but it did not change the LH pulse amplitude. I.v. injection of 5 mg/kg bicuculline (BIC), a GABAA receptor antagonist, during continuous infusion of MUS (5 mg/kg/h) which decreased the basal MUA and prevented the MUA volley from occurring, evoked MUA volleys and LH pulses whose amplitudes were similar to those found before the MUS infusion. Injection of the same dose of BIC during the infusion of saline increased the MUA transiently, but this increase was not accompanied by an LH pulse and afterwards there occurred MUA volleys at ordinary intervals accompanied by LH pulses with unchanged pulse amplitudes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Acute estradiol modulation of electrical activity of the LHRH pulse generator in the ovariectomized rat: restoration by naloxone.

Whether estrogen has the brain as a site of its negative feedback action was investigated by checking the acute effect of estradiol-17 beta (E2) on the electrical activity of the luteinizing hormone-releasing hormone (LHRH) pulse generator in ovariectomized rats fitted with chronically implanted electrode arrays in the medial basal hypothalamus. Before subcutaneous E2 implantation, the hypothalamic multiunit activity (MUA) exhibited, at an average frequency of 2.43/h, characteristic increases (volleys), each of which was associated with the initiation of an LH pulse. Within 2 h after E2 implantation, the frequency of MUA volleys was reduced significantly, probably associated with decreases in the frequency of LH pulses. The decrease in the amplitude of LH pulses occurred later than 2 h, but this effect was considered not to be mediated by the brain since the duration of MUA volleys was not changed. Since the mean serum LH concentration started to decrease within 2 h after E2 implantation, it was concluded that the acute inhibitory E2 effect on LH release is mediated by the brain. On the day after E2 implantation, intravenous infusion of naloxone (2 mg/kg/h) promptly elicited intermittent MUA volleys each of which was associated with an LH pulse. This suggests that operation of the LHRH pulse generator in the ovariectomized condition is restrained by the action of E2 with the mediation of endogenous opioid peptide neurons.

Animals↗

PubMed1993

Effects of gamma-aminobutyric acid-A receptor antagonist, bicuculline, on the electrical activity of luteinizing hormone-releasing hormone pulse generator in the ovariectomized rat.

The role of GABA neurons in the control of pulsatile release of LHRH was investigated by checking the effect of the GABAA receptor agonist, muscimol, and antagonist, bicuculline, on the electrical activity of the luteinizing hormone-releasing hormone (LHRH) pulse generator in the ovariectomized rat fitted with chronically implanted electrode arrays in the medial basal hypothalamus. In untreated control animals, the hypothalamic multiunit activity (MUA) exhibited, at an average of 20.5-min intervals, characteristic increases (volleys), each of which was associated with the initiation of an LH pulse. A bolus i.v. injection of muscimol (2 mg/kg) significantly increased the interval between MUA volleys and LH pulses without affecting the pulse amplitude. Continuous i.v. infusion of saline increased the interval between MUA volleys to an average of 24.1 min without affecting the LH pulse amplitudes. Bicuculline infusion (10 mg/kg/h) altered neither the interval between MUA volleys nor the pulsatile release of LH. This was further checked in the condition where presynaptic inhibition by opioid peptides on the noradrenergic system was presumably decreased by naloxone. Naloxone infusion (0.5 or 0.7 mg/kg/h) caused the MUA volleys to occur markedly frequently, an average of 13.8-min intervals. The interval during combined infusion of bicuculline with naloxone was an average of 16.2 min, suggesting that bicuculline could not decrease the interval that was set by naloxone. The results show that, although exogenous GABAA receptor agonist is capable of inhibiting the activity of LHRH pulse generator, the reduction in the endogenous GABAA receptor activity does not cause a significant effect, suggesting a minor role of inhibitory GABA neurons in the control of pulsatile release of LHRH. Further, together with the well-known fact that activation of GABAA receptor hyperpolarizes neurons postsynaptically, it is assumed that the GABAergic system, unlike the opioidergic one, is not involved in the presynaptic inhibition of the adrenergic receptor system which is probably implicated in the frequency control of LHRH pulse generator.

Animals↗

PubMed1993

Effect of low-osmolality contrast media on red cell filterability.

The effects of low-osmolality contrast media (CM) on red blood cell (RBC) filterability were investigated using a recently developed nickel mesh filtration method. The conventional hypertonic CM iothalamate, low-osmolality iohexol, and the recently synthesized iomeprol were studied. Among them, the osmolality of iomeprol was the lowest. The impact of CM osmolality, viscosity, and iodine content on the RBC filterability was analyzed. Under equal iodine content or viscosity condition, the filterability order of RBCs suspended in CM was iomeprol > iohexol >> iothalamate, because of the osmolality of CM. Iomeprol caused small echinocytic changes but these had a negligible influence on RBC filterability. In conclusion, the osmotic effect of CM on RBC filterability is more predominant than the other CM effects, and iomeprol is the preferred CM for RBC filterability.

Adult↗

PubMed1992

Hypothalamic electrical activity that relates to the pulsatile release of luteinizing hormone exhibits diurnal variation in ovariectomized rats.

The multiunit activity (MUA) was recorded in the arcuate nucleus-median eminence region in freely moving ovariectomized rats maintained under controlled lighting conditions (lights on 05.00-19.00 h) over a period of 24 h. The MUA of each rat had been confirmed to exhibit characteristic increases (volleys) in association with pulses of luteinizing hormone. In 6 MUAs examined, the frequency of MUA volleys was significantly greater in the dark period than in the light period, suggesting a diurnal variation in the release of luteinizing hormone-releasing hormone in the ovariectomized rat.

Animals↗

PubMed1992

[Electrophysiological studies on the hypothalamic GnRH pulse generator].

Gonadal function in mammals depends on gonadotropins secreted from the pituitary gland in a pulsatile manner. This pulsatility is governed by the periodic activation of the hypothalamic GnRH pulse generator. By means of multiple unit activity (MUA) recording techniques, characteristics increases in the neuronal activity, each of which is associated with the initiation of pulsatile LH secretion, have been recorded in the medial basal hypothalamus of the monkey, rat and goat. An unambiguous unitary relationship between the increased electrical activity (volley) and the LH pulse under a variety of physiological and experimental conditions indicates that the MUA volleys represent the electrical activity of the GnRH pulse generator. Hypothalamic MUA recordings provide direct access to the central component of the neuroendocrine control system which governs reproductive function.

Animals↗

PubMed1991

Intraventricular injection of vasoactive intestinal polypeptide facilitates the development of amygdaloid kindling.

To determine the involvement of vasoactive intestinal polypeptide (VIP) in the development of kindling in rats, VIP or antibody to VIP (anti-VIP) was injected into the third ventricle after the daily stimulation of the basolateral amygdala. The number of stimulations required to reach full amygdaloid kindling was significantly smaller in rats treated with VIP than rats treated with saline, whereas it increased significantly in rats treated with anti-VIP compared to that in the rats treated with either saline or normal rabbit serum. The results suggest that VIP participates in the development of amygdaloid kindling as a facilitatory factor.

Amygdala↗

PubMed1991

Naloxone increases the frequency of the electrical activity of luteinizing hormone-releasing hormone pulse generator in long-term ovariectomized rats.

Characteristic increases in neuronal activity accompanied by the initiation of each luteinizing hormone (LH) pulse have been successfully recorded in freely moving ovariectomized rats by means of multiunit activity (MUA) recording techniques. In the present study, the effect of the opioid receptor antagonist naloxone on this neuronal activity was examined in rats ovariectomized for 6-10 weeks. Electrodes were chronically implanted into the medial basal hypothalamus (n = 78) or the medial preoptic area (n = 29). During the MUA recording, blood samples were taken through an indwelling atrial cannula at 3- or 6-min intervals to determine the serum LH concentration. Naloxone was administered intravenously for 1 h by either intermittent injection every 6 min (0.05 mg/kg, 10 times) or continuous infusion (0.1, 0.2 and 0.5 mg/kg/h). Explosive rises in the MUA (volleys) associated with the initiation of LH pulse were recorded in 7 animals in which the tips of electrodes were located in the arcuate nucleus-median eminence region. In 5 animals studied, the mean (+/- SE) duration and interval of the MUA volleys were 2.1 +/- 0.1 and 22.1 +/- 0.9 min, respectively. Naloxone given every 6 min significantly increased the duration to 2.6 +/- 0.1 min, and decreased the interval to 9.5 +/- 0.9 min. This naloxone treatment disturbed the clear pulsatility of LH secretion observed in the pretreatment control period. Analysis of the effects of naloxone infused at 3 different doses revealed that the facilitatory effects of naloxone on the duration and frequency of the MUA volleys were dose-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Interactions between the noradrenergic and opioid peptidergic systems in controlling the electrical activity of luteinizing hormone-releasing hormone pulse generator in ovariectomized rats.

The effects of noradrenergic and opioid peptidergic receptor blockade, either alone or in combination, on the electrical activity of luteinizing hormone-releasing hormone (LHRH) pulse generator were studied in ovariectomized rats fitted with chronically implanted electrode arrays in the medial basal hypothalamus. Both alpha- and beta-adrenergic receptor antagonists, i.e. phenoxybenzamine (5 mg/kg i.v.) and propranolol (5 mg/kg i.v.), respectively, significantly increased the intervals between characteristic increases (volleys) in hypothalamic multiunit activity (MUA), which were associated with the initiation of LH pulses. In contrast to this, an opioid receptor antagonist naloxone (2 mg/kg i.v.) significantly decreased the intervals between the MUA volleys. Naloxone given after the injection of propranolol induced MUA volleys with a latency of a few minutes. However, when given after the injection of phenoxybenzamine, naloxone failed to induce such immediate MUA volleys. These changes in the intervals between the MUA volleys were faithfully reflected by the pulsatile LH secretion. These results suggest that norepinephrine facilitates LHRH pulse generator activity through both alpha- and beta-adrenergic-receptors, and that the action of opioid peptides on it requires an alpha-adrenergic receptor-mediated mechanism.

Animals↗

PubMed1989

LHRH injected into the medial preoptic area potentiates LH secretion in ovariectomized estrogen-primed and proestrous rats.

To determine if luteinizing hormone releasing hormone (LHRH) might act within the central nervous system to modulate its own secretion, microinjection of LHRH into the medial preoptic area (MPO) was performed at 13:00 h in both the ovariectomized estrogen-primed and proestrous rat, and the effects on the afternoon rise in the serum concentration of luteinizing hormone (LH) were studied. Microinjection of 5 ng LHRH into the MPO in the ovariectomized estrogen-primed rat resulted in a significant increase in serum LH from 16:00 to 19:00 h compared to the value in the saline-injected rat, whereas the injection at a dose of 2 ng did not induce a significant change. The injection of 5 ng LHRH into the third ventricle in the ovariectomized estrogen-primed rat induced a transient increase in serum LH immediately after the injection, followed by recovery to the preinjection concentration by 1 h, indicating that the potentiating effect of 5 ng LHRH in the MPO was not due to the LHRH leaked into the third ventricle. Finally, microinjection of 5 ng LHRH in the proestrous rat induced an early increase in serum LH, resulting in an advancement of the peak of the afternoon rise by 1 h. It is suggested that LHRH secreted in the MPO may, directly or indirectly, stimulate its own secretion in the median eminence to produce the surge of LH secretion.

Animals↗

PubMed1989

[A case of temporal arteritis associated with marked elevation of serum IgG, IgA levels].

An 84-year-old woman was admitted to Tokyo Metropolitan Tama Geriatric Hospital because of knee pain, anemia and hyperglobulinemia. On physical examination, evidence of arthritis was observed in both knees. Nodular temporal arteries were palpable with hypertrophy and weak pulsation. The urine was normal except that the sediment contained 20-30 with blood cells per high power view. Laboratory data showed raised erythrocyte sedimentation rate of 150 mm per hour, elevation of beta and gamma globulin and mild anemia. Although the levels of serum IgG, IgA were markedly increased, there was no monoclonal component on immunoelectrophoresis. Light microscopy examination of an aspirated specimen of bone marrow showed slight hypocellularity and mild plasmacytosis. However, atypical plasma cells were not observed. Radiographs of the knee showed narrowing of the joint space and calcification of articular cartilage and meniscus. Biopsy of the left temporal artery revealed typical findings of giant cell arteritis. The administration of prednisolone resulted in rapid normalization of laboratory findings. But her arthralgia, which had been relieved by analgesics after admission, was worsened if she took prednisolone without analgesic. Therefore, analgesics were given again with prednisolone for the control of the arthralgia.

Aged↗