Biomedical subjects

H Miyashita

Publications and source records attributed to H Miyashita.

At least 19 recordsLinked to original sources

PubMed1999

Effective control of Epstein-Barr virus-related hemophagocytic lymphohistiocytosis with immunochemotherapy. Histiocyte Society.

The familial form of hemophagocytic lymphohistiocytosis (HLH) is a lethal disorder. Although the prognosis for Epstein-Barr virus-associated HLH (EBV-HLH) remains uncertain, numerous reports indicate that it can also be fatal in a substantial proportion of cases. We therefore assessed the potential of immunochemotherapy with a core combination of steroids and etoposide to control EBV-HLH in 17 infants and children who met stringent diagnostic criteria for this reactive disorder of the mononuclear phagocyte system. Treatment of life-threatening emergencies was left to the discretion of participating investigators and typically included either intravenous Ig or cyclosporin A (CSA). Five patients (29%) entered complete remission during the induction phase (1 to 2 months), whereas 10 others (57%) required additional treatment to achieve this status. In 2 cases, immunochemotherapy was ineffective, prompting allogeneic bone marrow transplantation. Severe but reversible myelosuppression was a common finding; adverse late sequelae were limited to epileptic activity in one child and chronic EBV infection in 2 others. Fourteen of the 17 patients treated with immunochemotherapy have maintained their complete responses for 4+ to 39+ months (median, 15+ months), suggesting a low probability of disease recurrence. These results provide a new perspective on EBV-HLH, showing effective control (and perhaps cure) of the majority of EBV-HLH cases without bone marrow transplantation, using steroids and etoposide, with or without immunomodulatory agents.

Child↗

PubMed1999

Acute effect of tumor necrosis factor-alpha is minimal on mechanics but significant on energetics in blood-perfused canine left ventricles.

OBJECTIVES: We hypothesized that tumor necrosis factor-alpha (TNF-alpha) acutely alters left ventricular mechanoenergetics in blood-perfused hearts. To test this hypothesis, we examined the relation between left ventricular mechanics and energetics, both before and after infusion of TNF-alpha. DESIGN: Prospective, experimental study. SETTING: Research laboratory. SUBJECTS: Nine isolated, blood-perfused canine hearts. INTERVENTIONS: Recombinant human TNF-alpha (90 microg/min) was infused into the coronary circulation of the isolated hearts for 20 mins. MEASUREMENTS AND MAIN RESULTS: In the isolated, cross-circulated, blood-perfused canine left ventricles, left ventricular contractility was assessed through measurement of end-systolic elastance (Ees). Energetics were examined in terms of the end-systolic pressure-volume area-myocardial oxygen consumption (MVo2) relation. TNF-alpha concentration in coronary venous blood was >1000 ng/mL throughout the experiments. Nevertheless, infusion of TNF-alpha barely affected contractility acutely, i.e., there was a minimal decrease during the infusion (8.1+/-2.8% at 10 mins, p < .01) and a minimal increase after the infusion (11.2+/-2.5% at 10 mins, p< .01). Neither did the TNF-alpha infusion affect the slope of the end-systolic pressure-volume area-MVo2 relation. This finding indicated that the chemomechanical conversion efficiency remained unchanged. However, TNF-alpha infusion significantly increased the oxygen cost of contractility by 40% (1.25+/-0.13 vs. 1.75+/-0.24 mL oxygen.mL/mm Hg/beat, p< .05), indicating that MVo2 for the excitation-contraction coupling increased. CONCLUSIONS: TNF-alpha minimally alters left ventricular mechanics, but significantly changes energetics. The latter effect may result from changes in intracellular calcium handling.

Animals↗

PubMed1999

Simultaneous identification of static and dynamic vagosympathetic interactions in regulating heart rate.

We earlier reported that stimulation of either one of the sympathetic and vagal nerves augments the dynamic heart rate (HR) response to concurrent stimulation of its counterpart. We explained this phenomenon by assuming a sigmoidal static relationship between nerve activity and HR. To confirm this assumption, we stimulated the sympathetic and/or vagal nerve in anesthetized rabbits using large-amplitude Gaussian white noise and determined the static and dynamic characteristics of HR regulation by a neural network analysis. The static characteristics approximated a sigmoidal relationship between the linearly predicted and the measured HRs (response range: 212.4 +/- 46.3 beats/min, minimum HR: 96.0 +/- 28.4 beats/min, midpoint of operation: 196.7 +/- 31.3 beats/min, maximum slope: 1.65 +/- 0.51). The maximum step responses determined from the dynamic characteristics were 7.9 +/- 2.9 and -14.0 +/- 4.9 beats. min-1. Hz-1 for the sympathetic and the vagal system, respectively. Because of these characteristics, changes in sympathetic or vagal tone alone can alter the dynamic HR response to stimulation of the other nerve.

Acoustic Stimulation↗

PubMed1998

A photosystem I reaction center driven by chlorophyll d in oxygenic photosynthesis.

A far-red type of oxygenic photosynthesis was discovered in Acaryochloris marina, a recently found marine prokaryote that produces an atypical pigment chlorophyll d (Chl d). The purified photosystem I reaction center complex of A. marina contained 180 Chl d per 1 Chl a with PsaA-F, -L, -K, and two extra polypeptides. Laser excitation induced absorption changes of reaction center Chl d that was named P740 after its peak wavelength. A midpoint oxidation reduction potential of P740 was determined to be +335 mV. P740 uses light of significantly low quantum energy (740 nm = 1.68 eV) but generates a reducing power almost equivalent to that produced by a special pair of Chl a (P700) that absorbs red light at 700 nm (1.77 eV) in photosystem I of plants and cyanobacteria. The oxygenic photosynthesis based on Chl d might either be an acclimation to the far-red light environments or an evolutionary intermediate between the red-absorbing oxygenic and the far-red absorbing anoxygenic photosynthesis that uses bacteriochlorophylls.

Journal Article↗

PubMed1998

Photochemically induced focal cochlear lesions in the guinea pig: II. A transmission electron microscope study.

Photochemically induced focal lesions in guinea pig cochleas were studied by light microscopy and transmission electron microscopy. The lesions were induced in the second cochlear turns of 35 adult guinea pigs by illumination for 10 minutes with a focused green light immediately after a rose bengal solution was injected into the jugular vein. The cochlear lateral wall and organ of Corti were examined 5, 10, 20, 30, and 90 minutes, 12 and 24 hours, and 3, 7, and 30 days after the procedure. Aggregations of platelets and red blood cells were found in strial capillaries at 5 minutes after illumination. After 30 minutes, marginal cell surfaces protruded into the endolymphatic space; surface membranes were ruptured and the cytoplasm was expelled into the space. In outer hair cells, disruption of the cellular membrane was found near the cuticular plate 12 hours after the procedure. All cellular elements of the lateral wall and organ of Corti were markedly degenerated in the 30-day specimens. Histological changes found in the stria vascularis were consistent with cell damage caused by active oxygen species. It is likely that the stria vascularis is more sensitive to the photochemical reaction than other parts of the cochlea. Cell damage in other parts of the cochlea seemed to have been caused by local microvascular ischemia in addition to the action of active oxygen species induced by the photochemical reaction.

Animals↗

PubMed1998

Postischemic treatment with calpain inhibitor MDL 28170 ameliorates brain damage in a gerbil model of global ischemia.

The newly-developed calpain inhibitor, MDL 28170 penetrates the blood-brain barrier and inhibits brain cysteine protease activity after systemic administration. This experiment was initiated to determine if the calpain inhibitor, MDL 28170 could, by these actions, reduce neuronal damage in an animal model of global cerebral ischemia in the gerbil. The calpain inhibitor, MDL 28170 (50 mg/kg), was initiated at 0.5 and 3 h of recirculation following 5min of global ischemia. Animals subjected to ischemia but without treatment or with vehicle treatment served as controls. Evaluation by light microscopy was carried out on paraffin-embedded brain sections of gerbils which were sacrificed 7 days post-operatively. The results show that the calpain inhibitor, MDL 28170, protects against cortical neuronal damage even if the treatment is delayed until 3 h after reperfusion. However, the neuroprotective effect of this agent is less pronounced in the hippocampal CA1 sector. The results suggest that calpain-mediated proteolysis plays an important role in neuronal death due to ischemia. However, additional mechanisms by which an increased intracellular calcium concentration leads to neuronal death may exist.

Animals↗

PubMed1998

Acute glucosuria after continuous glucocorticoid loading in the rat in vivo.

We investigated the effects of the continuous infusion of various steroids in rats on renal tubular reabsorption of glucose in vivo to elucidate the pathogenesis of steroid-induced glucosuria. Urinary glucose excretion increased 60 min after administration of dexamethasone (2.38 mM). By 120 min, urinary excretion of glucose was three times higher in the dexamethasone group than in the control group (24.1 +/- 4.6 versus 72.4 +/- 16.7 micromol); the plasma level of glucose did not increase. Dexamethasone had no effect on the resorption of 1,5-anhydro-D-glucitol, which is a glucose-resembling polyol that is actively absorbed by the renal tubules as glucose. Neither estradiol nor progesterone increased urinary excretion of glucose. These findings suggest that continuous administration of a high-dose glucocorticoid selectively influences the glucose reabsorption system in the kidney.

Animals↗

PubMed1998

An increase in extracellular glutamate is a sensitive method of detecting ischaemic neuronal damage during cranial base and cerebrovascular surgery. An in vivo microdialysis study.

All patients undergoing neurological surgery are at risk for serious complications. Ischaemic damage presenting with hemiparesis or speech difficulties occurs in up to 6% of patients undergoing cerebral bypass procedures and other complicated neurosurgical procedures. Currently available methods for detection of such damage include the use of somatosensory evoked potentials (SSEPs) and electro-encephalography (EEG). Unfortunately, these techniques have false positives and may remain normal in the presence of severe focal neurological deficits. Early detection of potential deficits may prevent or minimize damage through a change in operative or anaesthetic strategy. With the availability of several potential neuroprotective compounds, it is also possible to treat patients at risk of developing ischaemic complications if the individuals are identified early. The excitatory neurotransmitter glutamate is not only a metabolic product, but is also thought to promote ischaemia induced cell injury if released into the extracellular space. It may be a significant parameter for ischaemic brain metabolism. In this report we describe 10 patients who underwent extracranial-intracranial (EC-IC) high flow bypass procedures with routine intra-operative monitoring (IOM) as well as intra-operative in-vivo microdialysis measurement of glutamate. Our aim was to compare intra-operative microdialytic findings and IOM findings with respect to patients' early postoperative clinical courses. Three patients had significant intra-operative glutamate increases indicating ischaemia. Two of these patients awoke with a new neurological deficit (hemiparesis). Routine IOM findings were either normal or showed only transient changes during the time the glutamate levels were high. Our study shows that an increase in extracellular glutamate, as monitored by in-vivo microdialysis, is an excellent early market of neuronal damage. While our glutamate measurements were done off-line, it may be possible to get in future continuous on-line measurements to serve as an early warning system for potential ischaemic damage.

Adult↗

PubMed1998

Focal damage to cochlear microcirculation measured using a non-contact laser blood flowmeter in guinea pigs.

The focal microcirculation damage induced by a photochemical reaction in the stria vascularis (SV) of the guinea pig cochlea was evaluated using a non-contact laser blood flowmeter (NCLBF) and the endocochlear potential (EP). Focal degeneration, including vascular thrombosis in the SV produced by the systemic infusion of rose bengal, and the illumination of green light in the second cochlear turn were observed with scanning and transmission electron microscopy. The NCLBF probe was placed at a position 10 mm from the cochlear surface, and the diameter of the laser light was focused to 1 mm in the green light illumination area. The change in NCLBF values induced by the loading of anoxia and administration of epinephrine agreed very well with those obtained with a conventional contact-type laser Doppler flowmeter. Significant decreases in the cochlear blood flow (CBF) (p < 0.01) and EP (p < 0.01) were observed at the site of the photochemical injury compared with the values at the non-illuminated area. CBF gradually decreased (82.0+/-7.3% at 10 min, 71.2+/-5.5% at 20 min, 64.3+/-11.2% at 30 min from the baseline, n=7), but blood pressure was stable. The EP values also decreased gradually during the first 13 min (79.9+/-3.7 mV at pre-illumination, 11.4+/-10.7 mV at 13 min, n=7). The gradual decline in the EP was comparable to the changes in the CBF. The NCLBF was useful for evaluating the haemodynamic properties of the cochlear microcirculation disorders, and this animal model is expected to be suitable for studying the pathology of focal cochlear vascular disease.

Animals↗

PubMed1998

Dynamic transduction properties of in situ baroreceptors of rabbit aortic depressor nerve.

We developed a new method for isolating in situ baroreceptor regions of the rabbit aortic depressor nerve (ADN) and estimated the transfer function from pressure to afferent nerve activity in the frequency range of 0.01-5 Hz by a white noise technique. Complete isolation of the baroreceptor area of the right ADN was made in situ by ligation of the innominate artery and the right subclavian and common carotid arteries. We altered the pressure in the isolated baroreceptor area according to a binary quasi-white noise between 80 and 100 mmHg in 12 urethan-anesthetized rabbits. The gain increased two to three times as the frequency of pressure perturbation increased from 0.01 to 2 Hz and then decreased at higher frequencies. The phase slightly led below 0.2 Hz. The squared coherence value was > 0.8 in the frequency range of 0.01-4 Hz. The step responses estimated from the transfer function were indistinguishable from those actually observed. We conclude that the baroreceptor transduction of the ADN is governed by linear dynamics under the physiological operating pressure range.

Afferent Pathways↗

PubMed1998

ESPVR of in situ rat left ventricle shows contractility-dependent curvilinearity.

We developed a miniaturized conductance catheter for in situ rat left ventricular (LV) volumetry. After the validation study of the conductance volumetry in 11 rats, we characterized the end-systolic pressure-volume relationship (ESPVR) in 24 sinoaortic-denervated, vagotomized and urethan-anesthetized rats. Stroke volume (SV) measured with the conductance catheter correlated closely with that measured by electromagnetic flowmetry (r > 0.95). No significant difference was found between the in situ LV end-diastolic volumes measured by conductance volumetry and postmortem morphometry; a linear regression analysis indicated that the correlation coefficient was 0.934, that the slope was not significantly different from 1, and that the intercept was not significantly different from 0. During cardiac sympathotonic conditions, the ESPVR was curvilinear. The estimated slope of ESPVR (end-systolic elastance, Ees) by quadratic curve fitting at end-systolic pressure of 100 mmHg was 2,647 +/- 846 mmHg/ml. Bilateral cervical and stellate ganglionectomy depressed contractility and made the ESPVR linear; a quadratic equation did not improve the fit. Ees was 946 +/- 55 mmHg/ml with the volume-axis (V0) intercept of 0.076 +/- 0.007 ml. Administration of propranolol (1 mg/kg) further reduced Ees (573 +/- 61 mmHg/ml, P < 0.001) and increased V0 slightly (0.091 +/- 0.011 ml). We conclude that the conductance catheter method is useful for the assessment of the ESPVR of the in situ rat left ventricle and that the ESPVR displays contractility-dependent curvilinearity.

Animals↗

PubMed1998

Dynamic sympathetic regulation of left ventricular contractility studied in the isolated canine heart.

We investigated the dynamic sympathetic regulation of left ventricular end-systolic elastance (Ees) using an isolated canine ventricular preparation with functioning sympathetic nerves intact. We estimated the transfer function from both stellate ganglion stimulation to Ees and ganglion stimulation to heart rate (HR) for both left and right ganglia by means of the white noise approach and transformed those transfer functions into corresponding step responses. The HR response was much larger with right sympathetic stimulation than with left sympathetic stimulation (4.3 +/- 1.4 vs. 0.7 +/- 0.6 beats . min-1 . Hz-1, P < 0.01). In contrast, the Ees responses without pacing were not significantly different between left and right sympathetic stimulation (0.72 +/- 0.34 vs. 0.76 +/- 0. 42 mmHg . ml-1 . Hz-1). Fixed-rate pacing significantly decreased the Ees response to right sympathetic stimulation (0.53 +/- 0.43 mmHg . ml-1 . Hz-1, P < 0.01), but not to left sympathetic stimulation (0.67 +/- 0.32 mmHg . ml-1 . Hz-1, not significant). Although the mechanism by which the sympathetic nervous system regulates cardiac contractility is different depending on whether the left or right sympathetic nerves are activated, this difference does not affect the apparent response of Ees to dynamic sympathetic stimulation.

Animals↗

PubMed1998

Accumulation of cAMP augments dynamic vagal control of heart rate.

Recent investigations in our laboratory using a Gaussian white noise perturbation technique have shown that simultaneous sympathetic stimulation augmented the gain of the transfer function from vagal stimulation frequency to heart rate response. However, the mechanism of that augmentation remains to be elucidated. In this study, we examined in anesthetized rabbits how three pharmacological interventions known to cause intracellular accumulation of cAMP affected the transfer function. Isoproterenol (0.3 microg . kg-1 . min-1 iv) increased the dynamic gain of transfer function from 7.12 +/- 0.67 to 12.4 +/- 1.21 beats . min-1 . Hz-1 (P < 0.05) without changing the corner frequency or the lag time. Similar augmentations were observed when forskolin (5 microg . kg-1 . min-1 iv) or theophylline (20 mg/kg iv) was administered under conditions of beta-adrenergic blockade. These results suggest that the accumulation of cAMP at postjunctional effector sites contributes, at least in part, to the sympathetic augmentation of the dynamic vagal control of heart rate.

Animals↗

PubMed1998

Cholinesterase affects dynamic transduction properties from vagal stimulation to heart rate.

Recent investigations in our laboratory using a Gaussian white noise technique showed that the transfer function representing the dynamic properties of transduction from vagus nerve activity to heart rate had characteristics of a first-order low-pass filter. However, the physiological determinants of those characteristics remain to be elucidated. In this study, we stimulated the vagus nerve according to a Gaussian white noise pattern to estimate the transfer function from vagal stimulation to the heart rate response in anesthetized rabbits and examined how changes in acetylcholine kinetics affected the transfer function. We found that although increases in the mean frequency of vagal stimulation from 5 to 10 Hz did not change the characteristics of the transfer function, administration of neostigmine (30 microg . kg-1 . h-1 iv), a cholinesterase inhibitor, increased the dynamic gain from 8.19 +/- 3.66 to 11.7 +/- 4.88 beats . min-1 . Hz-1 (P < 0.05), decreased the corner frequency from 0.12 +/- 0.05 to 0.04 +/- 0.01 Hz (P < 0.01), and increased the lag time from 0.17 +/- 0.12 to 0.27 +/- 0.08 s (P < 0.05). These results suggest that the rate of acetylcholine degradation at the neuroeffector junction, rather than the amount of available acetylcholine, plays a key role in determining the dynamic properties of transduction from vagus nerve activity to heart rate.

Acetylcholine↗

PubMed1998

Impact of endodontic conditions on marginal bone loss.

This study was undertaken to examine the extent to which the marginal alveolar bone may be influenced by the condition of the dental pulp. A total of 115 pairs of contralateral teeth were observed in 87 patients (25 to 45 years old) in which the test tooth, but not the control tooth, was either endodontically treated or not treated but with a periapical radiolucency. The distance from the cemento-enamel junction to the marginal bone level was measured using intraoral radiographs. The condition of the endodontic filling, the periapical status, and the presence of root canal post were also assessed. With clinical parameters similar between teeth in the two groups in terms of visible plaque, bleeding on probing, probing depth, and attachment level, the results showed a somewhat (mean value 0.1 mm; SD 0.7) larger reduction of the alveolar bone support in test than control teeth. This difference was not statistically significant on a patient level. Hence, this study failed to demonstrate a correlation between a reduced marginal bone support and endodontic status.

Adult↗

PubMed1998

Relationship between serum 1,5-anhydroglucitol and urinary excretion of N-acetylglucosaminidase and albumin determined at onset of NIDDM with 3-year follow-up.

OBJECTIVE: This prospective study was designed to elucidate the relationship between the serum level of 1,5-anhydroglucitol (1,5AG) and the urinary excretion of N-acetylglucosaminidase (NAG) and albumin in patients who were in the early stages of diabetes. RESEARCH DESIGN AND METHODS: A total of 1,062 male nondiabetic subjects with impaired glucose tolerance were monitored for blood glucose level once every 2-3 months, and the values were evaluated. Of these 1,062 subjects, 112 showed a worsening of glycemia during the observation period to the level seen in diabetes. We began to monitor the glycemia and parameters of renal damage in the 112 patients from the onset of diabetes. RESULTS: The urinary excretion of NAG and albumin were elevated even at the onset of diabetes. The abnormal excretion of NAG and albumin was associated with a change in serum 1,5AG and was quickly reversible when the serum 1,5AG improved. In the 3 years after the onset of diabetes, we obtained at least 18 measurements of one parameter for each patient and calculated the mean. Urinary NAG was found to be significantly correlated with the fasting plasma level of glucose (FPG; r = 0.512, P < 0.0001), the level of HbA1 (r = 0.351, P = 0.001), and the level of 1,5AG (r = -0.790, P < 0.0001). The urinary excretion of albumin was weakly but significantly correlated with levels of FPG (r = 0.383, P < 0.0001) and HbA1 (r = 0.337, P < 0.0001), but it was more strongly correlated with 1,5AG (r = -0.632, P < 0.0001). The level of 1,5AG was significantly correlated with FPG (r = -0.681, P < 0.0001) and HbA1 (r = -0.609, P < 0.0001). CONCLUSIONS: When the renal damage is not severe, the serum level of 1,5AG appeared to be an indicator of the reversible renal damage caused by hyperglycemia, as well as of the severity of the glycemia itself.

Acetylglucosaminidase↗

PubMed1998

Residual leukemic cell counts in the bone marrow at the end point of intensive induction therapy may be a prognostic factor for acute myeloblastic leukemia in adults.

Between January 1990 and May 1994, 59 previously untreated adult patients with acute myeloblastic leukemia (AML) were treated with a combination of behenoyl-cytosine-arabinoside (BHAC), daunorubicin (DNR), 6-mercaptopurine (6-MP) and prednisolone (PSL). Forty one patients (69.5%) achieved complete remission (CR). The Kaplan-Meier analysis revealed an actuarial probability for remaining in remission of 36% in patients who achieved remission and a survival of 29% in all patients at 5 years. A favorable factor relative to achieving CR was performance status (P=0.04). In addition the presence of 300 cells/microl or less of residual leukemic cell counts in the bone marrow at the end point of induction therapy tended to favor remission (P=0.06) using the multivariate analysis with a multiple logistic regression model. In addition the residual leukemic cells counts of less than 300/microl in the bone marrow at the end point of induction therapy was the most significant factor for durable remission (P=0.05) by the Cox's proportional hazard model. We concluded that residual leukemic cells counts in the bone marrow at the end point of intensive induction therapy is a valuable prognostic factor for adults receiving response-oriented individualized induction therapy for AML.

Adolescent↗

PubMed1997

Attenuated glutamate release during ischemia in ethanol-administered gerbils.

Previous studies have found an association between prior ethanol consumption and aggravated stroke outcome. Gerbils were intermittently given ethanol injections (s.c.) for 21 days at doses of 1 and 4 g/kg. After cessation of injections and appropriate weight gain, subjects underwent bilateral carotid occlusion while amino acid neurotransmitter levels in the hippocampus were monitored. Both the low and high dose ethanol groups demonstrated significantly decreased glutamate release compared with saline-treated controls during ischemia (p < 0.05). These results are consistent with a long-lasting ethanol-induced decrease in synaptic density in the hippocampus. That no intergroup differences on histological or neurobehavioral measures was found may suggest a functional dissociation of glutaminergic involvement in the pathogenesis of aggravated stroke outcome with alcoholism.

Animals↗