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Biomedical subjects

M Nishimura

Publications and source records attributed to M Nishimura.

At least 271 records · Page 15Linked to original sources

The role of Na,K-ATPase inhibitor on pressor responsiveness in patients with benign essential hypertension.

To clarify the role of Na,K-ATPase inhibitor in the enhanced pressor response to infused noradrenaline (NA-R) in patients with benign essential hypertension (EHT), NA-R, plasma noradrenaline concentration (PNA), and blood ionized calcium (Ca2+) were investigated before and after intravenous injection of ouabain in 15 normotensive subjects (NT) and 13 EHT. NA-R was enhanced by ouabain in both NT and EHT. The augmentation of NA-R following ouabain injection (delta NA-R) and % delta NA-R were significantly lower in EHT than in NT. Following ouabain injection, no significant change in PNA and blood Ca2+ was observed in both NT and EHT. NA-R negatively correlated with PNA and blood Ca2+, which were estimated just prior to noradrenaline infusion, before ouabain injection as well as after. After ouabain, the regression line between NA-R and PNA or blood Ca2+ shifted toward higher NA-R level in NT, unlike in EHT. These results suggest that an exogenous Na,K-ATPase inhibitor brings about a blunted enhancement of NA-R in EHT consistent with the presence of an endogenous Na,K-ATPase inhibitor in EHT.

Adult

Diabetic strain (WBN/Kob) of rat characterized by endocrine-exocrine pancreatic impairment due to distinct fibrosis.

A spontaneously developed endocrine-exocrine pancreatic dysfunction was observed in the aged males of an inbred strain of Wistar rats, WBN/Kob. Nonobese male WBN/Kob rats developed glycosuria and hyperglycemia at around 9 months of age. Cumulative incidence of diabetes in male rats was 43% (33 of 76) at 12 months of age and reached 90% at the age of 21 months. In contrast, female rats did not become diabetic. Urinary excretion of amylase in WBN/Kob rats was significantly increased in comparison with control Wistar rats. Moreover, the exocrine pancreatic function test was impaired in WBN/Kob rats. Pathological examination of pancreata revealed infiltration of inflammatory cells, hemorrhage, deposition of hemosiderin, and fibrinous exudation around pancreatic ducts and blood vessels at 3 months of age. A gradual increase of fibrous tissue into the exocrine tissue and islets was observed with advancing age. The extremely enlarged interlobular lymph nodes were also observed. At the age of 12 months, the fibrous tissue replaced extensive areas of the pancreas and involved islets. The amylase content of pancreata in WBN/Kob rats was markedly decreased in comparison with that in Wistar rats at 12 months of age. Islets composed of few endocrine cells were detected. Immunohistochemical staining for insulin and glucagon showed a decreased number of not only B cells but also A cells. Moreover, both the pancreatic insulin and glucagon contents were markedly decreased in WBN/Kob rats in comparison with Wistar rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases

Intracerebroventricular infusions of insulin increase vasopressin release in rats.

1. The role of cerebral insulin or insulin-like immunoreactive substance (ILI) on arginine-vasopressin (AVP) release using rats was investigated. Feeding rats with a high salt diet for 4 weeks significantly decreased the contents of ILI in both the hypothalamus and pituitary gland. Intracerebroventricular infusions of insulin (4 and 40 micrograms/min for 30 min) increased plasma AVP concentrations dose-dependently without hypoglycaemia, but decreased hypothalamic and pituitary contents of AVP. 2. These results indicate that ILI in the brain may play a role in the secretion of AVP, and that this mechanism could be operated to control a water-sodium balance.

Animals

A histopathological study on senile changes in the human olfactory bulb.

Senile changes in the human olfactory bulb were studied histopathologically in 133 individuals ranging in age from 40 to 91 years with a mean age of 64.3 years. Neurofibrillary tangles (NFTs) in the olfactory bulb were observed in 47 subjects aged over 50 years. The frequency of NFTs was 35.3% (47/133) in total and 40.5% (47/116) among subjects 50 years of age or older. The frequency of individuals with NFTs increased linearly with age. Senile plaques (SPs) were observed in 5 individuals over 60 years old at a frequency of 3.8% (5/133) in total and 5.7% (5/88) among individuals 60 years old or more. Granulovacuolar degeneration was rarely seen, and amyloid angiopathy was not recognized. Senile changes in the hippocampus and parahippocampal gyrus were also examined. In some cases, the frequencies of NFTs and SPs in the hippocampal region were not identical to those in the olfactory bulb. However, it was not apparent whether senile changes first appear in the olfactory bulb or in the hippocampal region.

Adult

Chronological observations of histological changes, cytochrome oxidase activity and copper level in the brain of the postnatal brindled mouse.

Neuropathological and enzyme-histochemical studies were performed on brindled mouse hemizygotes (BMs) and normal littermates at the age of 2 days, 7 days, 11 days and 14 days, together with an investigation of their tissue copper levels. A greatly increased copper concentration was confirmed in the kidney and intestine and a greatly reduced concentration in the liver and brain of BMs. The copper concentration in the brain increased gradually with age in the normal littermates, whereas this did not occur in BMs. There was no significant difference in the tissue copper concentration between the cerebrum and the cerebellum-brainstem in BMs or in normal littermates. Light and electron microscopy of the BM brain revealed progressive neuronal degeneration in association with increased mitochondrial changes (ballooning and crista disintegration). Enzyme histochemical examinations demonstrated a progressive comparative decrease (i.e., an increased difference from normal) of cytochrome oxidase activity in the BM brain. These data suggest that progressive degeneration of the brain in Menkes' disease is attributable to mitochondrial degeneration caused by a comparative decrease of both copper concentration and cytochrome oxidase activity in the brain.

Animals

Role of dopaminergic mechanisms in the kidney for the pathogenesis of hypertension.

1. To estimate the role of renal dopaminergic mechanisms in the pathogenesis of hypertension, patients with essential hypertension and animal models of hypertension were investigated. 2. Impaired dopaminergic activity in kidneys for natriuresis was observed in patients with 'salt-sensitive' hypertension and with low-renin hypertension. 3. Decreased dopaminergic activity in kidneys was observed in the Dahl S-rats without salt loading. 4. In spontaneously hypertensive rats, renal dopamine synthesis was enhanced whereas there was a decrease of adenylate cyclase activity in renal tubules. 5. Demonstration of impaired dopaminergic mechanisms in kidneys of human and animal hypertension suggests that renal dopaminergic mechanisms play an important role in development of hypertension.

Animals

Ryanodine facilitates calcium-dependent release of transmitter at mouse neuromuscular junctions.

1. Quantal release of transmitter was measured intracellularly at mouse neuromuscular junctions in the presence and absence of ryanodine (Rnd). 2. Rnd at concentrations up to 1 microM did not significantly alter the frequency of miniature endplate potentials (m.e.p.ps) in the presence or absence of Ca2+, suggesting that Rnd is unlikely to alter the internal concentration of Ca2+ ([Ca2+]i) at rest. 3. In a high-K+ (10 mM) bathing solution, Rnd further potentiated the facilitatory effect of Ca2+ on the frequency (F, s-1) of m.e.p.ps. Rnd shifted the relationship between 1n(F) and 1n[Ca2+]o to lower concentrations. 4. In a high-Mg2+ bathing solution, Rnd did not affect the frequency of m.e.p.ps at any value of [Ca2+]o. However, Rnd slightly but significantly increased the quantal content (m) of e.p.ps. It shifted the relationship between 1n(m) and 1n[Ca2+]o to lower concentrations. These results suggest that Rnd potentiates the quantal release of transmitter after depolarization of the membrane or nerve impulse, in keeping with the cooperativity of Ca2+ at the active site. 5. A series of two closely spaced nerve impulses produced a facilitation of transmitter release, as judged by the quantal content (m2) of the second response in relation to that of the first one (m1), m2/m1. Rnd did not change the ratio m2/m1. Thus Rnd is unlikely to affect the rapid phase of the sequestration of Ca2+ inside the nerve terminal. 6. High levels of K+ (5 mM) and caffeine (2 mM) potentiated both modes of transmitter release, in a manner dependent on [Ca2+]o. Caffeine did not potentiate facilitation of transmitter release. 7. These results indicate that Rnd facilitates the quantal release of transmitter presumably via an increase in [Ca2 ]i by a manner different from that of high-K+ or caffeine. The results suggest that Rnd probably affects calcium turnover in neuronal cells.

Alkaloids

High ratio of HTLV-1-infected cells in HTLV-1 associated myelopathy (HAM).

Sixteen patients with HTLV-1 associated myelopathy (HAM) were examined for the presence of HTLV-1 provirus genome by Southern blot analysis of genomic DNA from peripheral blood mononuclear (PBM) cells. Random integration of the provirus was detected in 14 of 16 HAM patients. By contrast, the provirus genome could not be detected in 6 non-HAM HTLV-1 carriers, HAM patients were found to have significantly higher antibody titer to HTLV-1 in the sera compared with carriers. These features of HAM patients, i.e., detectable levels of provirus integration in PBM cells and high antibody titer to HTLV-1 in the sera, were noted in 2 wives of HAM patients with neurological signs and abnormalities. High anti-HTLV-1 antibody titer and detection of the provirus genome by Southern hybridizations may be useful for screening subclinical HAM cases and elucidating pathogenesis.

Adult

Extramammary Paget's disease: comparative histopathologic studies of intraductal carcinoma of the breast and apocrine adenocarcinoma.

We examined 32 cases (38 lesions) of extramammary Paget's disease (EMPD) in relation to comparative studies on intraductal carcinoma of the breast (ductal carcinoma in situ, DCIS) and apocrine adenocarcinoma (AAC). Lesions included scrotum (18 lesions), vulva (8), axilla (6), groin (3), penis (2) and chest wall (1), and the distribution was compatible with that of apocrine or supernumerary mammary glands. Histologically, extra-mammary Paget's and DCIS cells exhibited a large amount of a pale-stained cytoplasm. The cytoplasm of AAC cells frequently contained granules, was eosinophilic and differed from that of Paget's or DCIS cells. Immunohistochemical studies revealed positive reactions for polyclonal and monoclonal antibodies to carcinoembryonic antigen in all EMPD and most DCIS, but not in AAC. Recent studies have shown that extramammary Paget's cells exhibit characteristics of glandular epithelial cells and that most cases of EMPD are not accompanied by an underlying carcinoma. The results obtained in this study, coupled with data on the frequency of the supernumerary breasts, lead to the speculation that extramammary Paget's cells originate from ectopic mammary glands or from pluripotential germinative cells in the epidermis, capable of differentiating toward the mammary glands.

Adenocarcinoma

[An in vitro study on the treatment of complicated cystitis using an automatic simulator].

A computer simulation of a Kidney-bladder model was prepared for automatic control of the urine concentration of antibacterial drug administrated. The following results were obtained in an investigation of the problems of complicated cystitis in vitro using ofloxacin. 1) It was suggested that the time required for elimination of the bacteria was prolonged as the level of complication of the disease state in the urinary tract increased. 2) In the model of highly complicated cystitis caused by urinary flow stagnation, recurrences were observed in vitro even with administration of a large dose of ofloxacin. 3) The time required for a elimination of bacteria tended to become shorter as the dose of the antibacterial agent increased. 4) The time until the start of regrowth of the bacteria tended to be prolonged as the dose of the antibacterial agent increased. 5) It was suggested by our in vitro experiment that if the background disease became more complicated, it would be more difficult to treat, as in the case of complicated cystitis.

Computer Simulation

[Study on auxotype and serotype of Neisseria gonorrhoeae].

The auxotypes of 592 strains of Neisseria gonorrhoeae isolated in Sapporo between 1980 and 1989 were investigated. The serotypes of some of these strains were also studied, and the relation between the auxotype and the sensitivity to Amoxicillin (AMPC) was analyzed. The results were as follows. 1. The auxotypes of Neisseria gonorrhoeae isolated in Sapporo were similar to those distributed in Southeast Asia. 2. In a study of the auxotypes by year, the frequency of proto and Pro- decreased, while the frequency of AHU- increased. 3. The serotypes of all strains of Neisseria gonorrhoeae investigated were WII/WIII, there was no WI serotype. 4. With respect to the relation between auxotypes and sensitivity to AMPC, the AHU- strains were more sensitive than proto or Pro-.

Amoxicillin

[Epidemiological study on Chlamydia trachomatis infection in pregnant housewives and investigation on its influence on outcome of pregnancy and on their newborns].

We surveyed Chlamydial infection with Chlamydiazyme for 3010 pregnant housewives in Hokkaido. Four hundred and fourty six out of the 3010 pregnant housewives were also be retrospectively investigated for the influence of C. trachomatis on outcome of pregnancy and on their newborns. The results were as follows. 1) Of the 3010 pregnant housewives, 217 (7.2%) were C. trachomatis-antigen positive, when their endocervical specimens were tested. There was no difference in the positive rate of C. trachomatis among the six cities where our investigation was performed. 2) A high C. trachomatis-positive rate (21.9%) was achieved in the pregnant teen-aged housewives with a significant decrease as age increased. 3) As for placenta previa, threatened abortion, preterm delivery and small for date infants, the incidence was higher in the untreated C. trachomatis positive group than in the C. trachomatis negative group. 4) The weeks of gestation and birth weight of newborns in the untreated C. trachomatis positive group were significantly lower than those of the C. trachomatis negative group. 5) No statistical significance was found in the incidence of premature rupture of membrane, fatal distress, spontaneous abortion nor postpartum fever between the C. trachomatis negative group and the untreated C. trachomatis positive group. These results suggest that Chlamydial infection in pregnant housewives is widely spread in Hokkaido and gives some disadvantage to pregnancy outcome and newborns. Consequently, Chlamydial infection in pregnant women must be appropriately diagnosed and treated in the early stage of pregnancy.

Abortion, Threatened

[Studies on the detection rate of Chlamydia trachomatis in married and unmarried pregnant women--field survey in Hokkaido].

Chlamydia trachomatis infection in the general population has recently been attracting attention. In this regard, we examined the incidence of positive antigen in the genital organs in pregnant female women in order to investigate the prevalence of this infection. EIA (Chlamydiazyme) was performed in 5,000 married pregnant women, and in 317 unmarried women who underwent artificial termination of pregnancy. The study was carried out between June 1986 and September 1989 in Sapporo City (3,932 subjects), Kushiro City (328 subjects), Muroran City (280 subjects), Kitami City (357 subjects), Kucchan Town (220 subjects) and Urakawa Town (200 subjects). 1. Among married pregnant women, the detection rate of C. trachomatis was 6.1% (222/3,666) in Sapporo City, 7.3% (24/328) in Kushiro City, 6.1% (17/280) in Muroran City, 7.8% (24/306) in Kitami City, 6.8% (15/220) in Kucchan Town and 7.5% (15/200) in Urakawa Town, showing no particular difference according to the area. The overall detection rate was 6.3% (317/5,000). 2. The rates of detection of C. trachomatis antigen by EIA were 22.9% (61/266) and 15.7% (8/15) for the unmarried women who underwent artificial termination of pregnancy in Sapporo and Kitami, respectively. Both rates were higher than those in the married pregnant women. This result suggests the prevalence of C. trachomatis among young women showing a high level of sexual activity. 3. Among married subjects, the detection rate was 21.3% for those in their late teens, 8.9% for those in their early 20s, 6.0% for those in their late 20s, 3.7% for those in their early 30s, and 2.9% for those 35 years or older; thus, the younger they were, the detection rate became elevated. The above findings show that latent epidemics of C. trachomatis infection are present to a considerable extent among young women.

Adolescent

Naloxone increases ventilatory response to hypercapnic hypoxia in healthy adult humans.

The ventilatory response to hypercapnic progressive hypoxia and the breathing pattern during steady-state hypercapnic hypoxia were compared before and after intravenous infusion of 3 mg of naloxone in a relatively large number of healthy adults (n = 21). In addition, the withdrawal response from hypercapnic hypoxia (modified transient O2 test) was measured to investigate the possible role of endogenous opioids in the peripheral chemoreceptors. The average ventilatory response (delta VE/delta SaO2) increased significantly from 0.51 +/- SD 0.26 to 0.65 +/- 0.42 L/min/% (p less than 0.05) after naloxone infusion, whereas there were no significant changes between two tests with normal saline in the control study (n = 7). Because there was considerable interindividual variation in the response to naloxone administration, we selected "high responders" (n = 8) who showed larger increases with naloxone than the upper limit of the 95% confidence interval for the change with the second saline in the control study. They showed greater delta VE/delta SaO2 (p less than 0.01), respiratory frequency (p less than 0.01), and mean inspiratory flow (p less than 0.01) during hypercapnic hypoxia before naloxone infusion than did the other subjects. There was no significant change in the withdrawal response before and after naloxone infusion, even in such high responders. We conclude that endogenous opioids participate in the control of breathing in normal adults during hypercapnic hypoxia. This may be particularly true for those subjects who exhibit greater chemosensitivity to hypercapnic hypoxia. Endogenous opioids appear to act centrally rather than peripherally.

Adult

Measurement of digital arterial pressure in patients with essential hypertension.

In 8 normotensive volunteers, digital blood pressure was determined, and the value was compared to direct brachial arterial pressure and to that measured by a conventional, indirect Korotkoff-method in the upper arm. The correlation coefficient was determined by changing blood pressure with intravenous administration of vasoconstrictors, sublingual nitroglycerin, and stress tests. Although the absolute value of the digital blood pressure was slightly lower than direct arterial pressure, the correlation between the two determinations was highly significant. The difference in readings between direct and digital arterial pressure was not significant even when the pressure was fluctuated with administration of vasoactive drugs and stress tests. In 2 of 6 volunteers the photosignals of the digital arterial pulses became too small to measure pressure 30 min after they entered in a cold room. However, the digital/brachial blood pressure difference did not alter even when the signals became small during the cold exposure in the remaining 4 subjects. Afterward, the subjects visited our outpatient clinic, where their digital blood pressure was taken. The value was compared with the indirect, contralateral brachial blood pressure. The absolute difference between the readings increased significantly when hypertension advanced. Among the patients (WHO, stage I) treated with antihypertensive drugs, the digital/arm pressure gap was the greatest in patients treated with beta-adrenergic blockers, diuretics and calcium channel blockers in decreasing order. These results indicate that digital blood pressure is influenced by the severity of hypertension and drugs; i.e., hypertensive vascular injury and/or atherosclerosis lowers the peripheral blood pressure leading to impaired peripheral tissue perfusion in the hypertensive patient, and beta-adrenergic blockers may deteriorate peripheral circulation in spite of their hypotensive effects.

Adult

Intracerebroventricular injections of endothelin increase arterial pressure in conscious rats.

We investigated the possible effects of endothelin (ET) on the central regulation of arterial pressure by injecting ET intracerebroventricularly (ICV) into conscious rats. ICV injections of ET caused dose-dependent elevation of arterial pressure and increase of heart rate. The first reaction was abolished by bunazosin, an alpha 1-adrenergic blocker, injected intravenously. However, the increase in arterial pressure and heart rate caused the rats, injected with ET ICV, to roll to the left on their long axis for 20-30 min, followed by prolonged sedation. Furthermore, the pressor responses and tachycardia were significantly attenuated by the ICV pretreatment with nicardipine, a calcium channel blocker, and nicorandil, a nitrate derivative, respectively. These results suggest that ET may elevate the intracellular Ca2+ concentration ([Ca2+]i) of sympathetic nerve activity regulatory neurons of the brain, leading to an accelerated outflow of sympathetic nerve activity and cause the elevation of arterial pressure.

Adrenergic alpha-Antagonists

Comparison of flow-resistive work load due to humidifying devices.

There are many kinds of humidifying devices. We evaluated six humidifiers from the viewpoint of AWLs. The AWL was obtained by calculating the area difference between pressure-volume tracings obtained without and with humidifiers. To examine the effect of pressure monitoring sites on AWL when a humidifier is placed, we measured AWL at three different pressure monitoring sites. The AWL was affected significantly by the pressure monitoring site for the ventilator. When a pressure monitor sensor was placed on the inspiratory limb between the inspiratory valve and humidifiers, the ventilator was not able to compensate for the pressure drop caused by impedance characteristics of the humidifier equipment. This resulted in significant inspiratory AWL on the patient. Thus, humidifying devices should be carefully selected from the viewpoint of not only humidifying capability but also AWL. Furthermore, we must recognize the importance of the pressure monitoring site for the ventilator.

Airway Resistance

Measurement of functional residual capacity during high-frequency oscillatory ventilation (HFOV) by argon washout method without interruption of HFOV.

A modified indicator gas washout method was developed to measure functional residual capacity (FRC) during high-frequency oscillatory ventilation (HFOV) without interruption of HFOV. A hot-wire flowmeter and medical gas analyzer measured the flow rate and argon concentration, respectively, at the expiratory end of the respiratory circuit. Upstream of the hot-wire flowmeter, two heat-and-moisture exchangers for resistance and a rubber balloon for capacitance were placed to convert the oscillating expiratory flow to an almost continuous flow. This made it possible to measure FRC during HFOV without interrupting HFOV. To measure the volume of the entire respiratory circuit, a 10 percent argon in 90 percent oxygen gas mixture was initially used as a bias flow, and after equilibration, the test gas was switched to 100 percent oxygen. By electrical integration of the product of the expiratory flow rate and argon concentration, the total amount of argon equilibrated in the entire respiratory circuit was calculated. The volume of the circuit was calculated by dividing the total amount of argon by the initial argon concentration. Functional residual capacity plus the volume of the respiratory circuit was similarly calculated and the difference was estimated as FRC. The accuracy and reproducibility of our method were evaluated by using a one-compartment lung model. There was a high correlation between the volume setting of the model lung and the estimated FRC. This method can be used to estimate FRC in a one-compartment lung model during HFOV, and it is potentially useful in clinical situations.

Argon