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Biomedical subjects

M Nishimura

Publications and source records attributed to M Nishimura.

At least 199 records · Page 11Linked to original sources

Evolutionary relationships between laboratory mice and subspecies of Mus musculus based on the restriction fragment length variants of the chymotrypsin gene at the Prt-2 locus.

Restriction endonuclease fragment length variants in mice were compared by Southern blot analysis using the cDNA probe pcXP33 for the chymotrypsin gene. The variants were detected in the restriction patterns generated by fragments from digestions with BglII, EcoRI, HindIII, Pstl, SacI, and XbaI. The set of protein phenotypes and the restriction patterns of chymotrypsin gene were examined in many laboratory strains and wild subspecies. Most laboratory strains (26 strains) are grouped into a set defined as Set 1, but only a few laboratory strains (AU/SsJ and five BALB/c sublines) are classified as belonging to Set 2. Of wild subspecies, only BRV-MPL (M. brevirostris) can be placed in Set 1, while DOM-BLG and SK/Cam (M. domesticus) belong in Set 2. The assignment of an appropriate set defined by the characteristics of the chymotrypsin gene has also been investigated in M. musculus, two Chinese subspecies, M. yamashinai, M. molossinus, and M. castaneus, and the evolutionary relationship between laboratory mice and various subspecies of Mus has been examined.

Animals

Clinico-histochemical studies on type 4 carcinoma of the stomach--with special reference to mucopolysaccharides and sialic acid in tumor tissue.

One hundred and twenty-one patients with gastric cancer of Borrman IV (type 4) were classified into two types according to the macroscopic appearance of their tumors, namely, those tumors with giant folds (type G, n = 84) and those without giant folds (type P, n = 37). A large percentage of the cases in both type groups had advanced stage carcinoma. Type G was found to be predominant in young women and the incidence of high-grade lymph node metastasis was higher in type G than in type P. Histochemically, it was shown that the tumor interstitium of type G contained obviously many more acid mucopolysaccharides (AMPS) than the localized Borrman II (type 2) gastric cancer, which was used as a control. The results of enzymatic digestion tests suggested that the amounts of hyaluronic acid, chondroitin sulfate, and sialic acid were greater in type G than in type P or the localized type, the differences involved being marked between type G and the localized type.

Adenocarcinoma

Preparation of monoclonal antibodies against okadaic acid prepared from the sponge Halichondria okadai.

Three murine monoclonal antibodies, OA-1, OA-2 and OA-3, against okadaic acid were prepared from hybridoma clones obtained by fusion of mouse 653 myeloma cells with mouse immune spleen cells sensitized to okadaic acid-ovalbumin conjugate. Each antibody reacted with dinophysistoxin-1 ( = 35-methylokadaic acid) as well as okadaic acid, but did not react with the other diarrhetic shellfish poisons or related compounds, such as 7-O-palmitoyl-okadaic acid (analogue of dinophysistoxin-3), pectenotoxin-1 and yessotoxin. A competitive inhibition enzymelinked immunosorbent assay which employed OA-3 antibody was performed and showed a sensitivity of about 10 ppb (10 ng/ml) for okadaic acid. This simple and time-saving ELISA assay system may be useful for the specific detection of diarrhetic shellfish poisons.

Animals

Arachidonic acid metabolites by cytochrome P-450 dependent monooxygenase pathway in bovine adrenal fasciculata cells.

[1-14C]Arachidonic acid was incubated with microsomes of bovine adrenal fasciculata cells in the presence of 1 mM NADPH for 30 min at 37 degrees C. The metabolites were separated and purified by reverse phase high performance liquid chromatography, and identified by gas chromatography-mass spectrometry. Identified metabolites were four dihydroxyeicosatrienoic acids (DHTs) (5,6-, 8,9-, 11,12-, 14,15-DHTs), 20-hydroxyeicosatetraenoic acid and eicosatetradioic acid. The formation of these metabolites was dependent on NADPH and inhibited by SKF-525A. 14,15-DHT was also formed by isolated bovine adrenal fasciculata cells. These results indicate that cytochrome P-450 dependent arachidonate monooxygenase pathway may exist in bovine adrenal fasciculata cells. Addition of the chemically synthesized epoxyeicosatrienoic acids (EETs) to isolated bovine adrenal fasciculata cells stimulated cortisol production. Among four regioisomeric EETs, 14,15-EET was most potent and stimulated steroidogenesis in a dose-related manner over a range of 0.5 to 5.0 microM.

8,11,14-Eicosatrienoic Acid

The influence of ouabain on twitch contractions in the presence of veratridine.

1. Direct stimulation evoked twitches in mouse diaphragm muscles in presence of 10 microM D-tubocurarine in vitro. Effects of ouabain and their dependence on K+ were examined on the twitch responses and action potentials in the presence and absence of twitch potentiators. 2. Ouabain inhibited twitch contractions only in the presence of veratridine, aconitine and monensin while it had no inhibitory effect on control twitches. The interactions between ouabain and these twitch potentiators depended on the presence of external K+, except in the case of monensin. 3. Removal of Ca2+ from a bathing solution accelerated the potentiating effect of veratridine and the antagonizing effect of ouabain. 4. Caffeine further potentiated the twitches which had been attenuated by ouabain combined with veratridine. 5. Ouabain combined with veratridine consistently decreased resting membrane potentials, action potentials and overshoot potentials and prolonged time to peak of and duration of the muscle action potentials. 6. Tetraethylammonium, 4-aminopyridine, and caffeine produced twitch potentiation which was insensitive to ouabain or the removal of K+. 7. These results suggest that twitch contractions in the presence of activators of sodium channels link with activation of Na+-K+-ATPase. Accumulation of Na+ inside the muscle fibres may uncouple the excitation-contraction system. 8. This uncoupling may not include the caffeine-sensitive process that controls the release of Ca2+ from the sarcoplasmic reticulum. Na+ accumulation may decrease transmembraneous gradient of this ions, thereby causing a reduction in excitation coupled with twitch contraction.

4-Aminopyridine

Nature of so-called "metaplasia of the apocrine epithelium". Macrophages attack apocrine epithelium". Macrophages attack apocrine epithelium.

Immunohistochemical and electron-microscopic studies were performed on the lesion termed "metaplasia of the apocrine epithelium." which was seen in association with an apocrine adenocarcinoma. The cells of this so-called "metaplasia" lacked cytokeratin, which was present in the apocrine epithelium. Surprisingly, the lesion ultrastructurally consisted mainly of terminally differentiated macrophages, the cytoplasms of which were filled with numerous phagosomes and lipid droplets. The cells lacked a desmosomal connection at their borders and some had Langerhans granule-like structures in the cytoplasm. The luminal wall was often infiltrated with macrophages and lymphocytes, and, in some portions, was replaced by macrophages with a large cytoplasm filled with numerous phagosomes. The immunohistochemical and ultrastructural findings indicate that the lesion is not composed of cells of the apocrine epithelial origin, but of macrophages that have ingested apocrine epithelium.

Aged

High-frequency oscillation for persistent fetal circulation after repair of congenital diaphragmatic hernia.

A female neonate who had been diagnosed as having congenital diaphragmatic hernia by ultrasonography was delivered by cesarean section. After the hernia was repaired, she developed hypoxemia and hypercapnia, probably due to persistent fetal circulation (PFC). Neither conventional mechanical ventilation (CMV) nor manual ventilation improved the respiratory status. High-frequency oscillation (HFO) successfully improved pulmonary gas exchange, but we failed to wean the patient from HFO by using intermittent HFO. The patient was again placed on CMV for weaning and was extubated on the 12th ICU day. We conclude that HFO can be an alternative respiratory modality in patients with respiratory failure due to PFC after the repair of congenital diaphragmatic hernia.

Female

Effects of norepinephrine on renal function in septic patients with normal and elevated serum lactate levels.

Effects of iv norepinephrine (NE) on renal function were investigated retrospectively in 15 patients with hyperdynamic septic shock. All patients had either a low systolic BP less than 80 mm Hg, and/or oliguria less than 0.5 ml/kg-h. We examined their serum creatinine level (SCr), daily urine flow (UF), 24-h creatinine clearance (Ccr), and hemodynamic indices before and during NE infusion. Before NE administration, the patients were divided into those with with a serum lactate level (Lac) less than 20 mg/dl (group A, n = 9) and greater than 20 mg/dl (group B, n = 6). NE was infused continuously at rates between 0.05 and 0.24 microgram/kg.min which increased systolic BP by greater than or equal to 20 mm Hg. Cardiac index was not significantly changed in either group. In group A, NE increased both UF (p less than .05), and systemic vascular resistance index (SVRI) (p less than .01), but did not affect Ccr. In group B, NE did not increase UF nor SVRI, and decreased Ccr significantly (p less than .05). It is concluded that NE increased UF and SVRI only when Lac was in normal range; otherwise, NE reduced renal function. Thus, when administering NE to increase UF, both Lac and renal function should be monitored carefully.

Adult

Malignant hidroacanthoma simplex.

A case of malignant hidroacanthoma simplex is described. Histological examination revealed that the malignant cells had arisen from a tumor cell nest of benign hidroacanthoma simplex and invaded the dermis. Two years and 7 months after the excision of the original thigh lesion, a groin lymph node metastasis was discovered. The metastatic tumor cells in the lymph node were histologically similar to the carcinoma cells in the original thigh lesion and had enzymatic and ultrastructural features resembling eccrine sweat duct.

Aged

The influence of ouabain on twitch potentiation by anticholinesterases in the phrenic nerve-diaphragm muscles of mice.

1. (+)-Tubocurarine, hexamethonium, atropine, ouabain, and removal of potassium from the bathing medium were examined for their effects on indirectly evoked twitches (IT) of mouse phrenic nerve-diaphragm muscles in the presence or absence of neostigmine. 2. Neostigmine increased the amplitude of IT. The twitch potentiation was reduced by (+)-tubocurarine at low concentrations that had no inhibitory effect on normal IT. Hexamethonium (10-100 microM), but not atropine (0.1-1 microM), partially inhibited the twitch potentiation. Neither hexamethonium nor atropine had an inhibitory effect on IT in the absence of neostigmine. 3. Ouabain (5 microM) abolished the twitch potentiation by neostigmine while having no inhibitory effect on directly evoked twitches in the presence of neostigmine and (+)-tubocurarine together. 4. The potentiating effect of neostigmine was less in a potassium-free bathing solution. The inhibitory effect of ouabain disappeared in this solution. 5. Reinclusion of KCl at 2.5 mM restored both the potentiating effect of neostigmine and the antagonistic effect of ouabain. This reinclusion did not potentiate IT in the absence of neostigmine. 6. An interaction resembling that between ouabain and neostigmine was obtained between ouabain and physostigmine or paraoxon. 7. Both endplate potentials (e.p.ps) and miniature e.p.ps increased in terms of their amplitude and duration in the presence of neostigmine. Ouabain did not reduce the enhanced endplate responses. 8. These results indicate that the potentiation of IT by anticholinesterases may occur via nicotinic receptors which are sensitive to both (+)-tubocurarine and hexamethonium, and that the interaction between anticholinesterases and ouabain depends on the presence of K+. It appears that the mechanisms of twitch potentiation are dependent on the ionic gradients maintained by Na+-K+-ATPase.

Animals

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

1. The effects of sodium salicylate on the frequency of miniature endplate potentials (m.e.p.ps) and on the quantal content of endplate potentials (e.p.ps) in mouse diaphragm muscles at 36 degrees C and 24 degrees C were studied by conventional microelectrode techniques. 2. At 36 degrees C, salicylate (10 mM) elevated the frequency of m.e.p.ps in a manner which was insensitive to [Mg2+]0 and independent of the presence of [Ca2+]0. Lowering the temperature to 24 degrees C abolished the stimulating effect. 2,4-Dinitrophenol (10 microM) had similar effects at 36 degrees C and these disappeared at 24 degrees C. All subsequent experiments were performed at 24 degrees C. 3. Salicylate (10 mM) further increased the frequency (F) of m.e.p.ps stimulated by [Ca2+]0 in a depolarizing solution. When [Ca2+]0 was varied in the absence of salicylate, a linear relationship between ln(F) and ln([ CA2+]0) was obtained. Salicylate shifted this relationship to the left, with respect to the control, without altering the slope. 4. Salicylate (5 mM) also increased the quantal content (m) of e.p.ps in a solution that contained 5 mM Mg2+, in a concentration-dependent fashion. As [Ca2+]0 was varied in the absence of salicylate, a linear relationship between ln(m) and ln[(Ca2+]0) was observed. Salicylate shifted this linear relationship to the left, with respect to the control, without altering the slope. Doubling the concentration of [Mg2+]0 antagonized this effect of salicylate on the quantal content of e.p.ps. 5. These results indicate that salicylate enhances the effect of changing [Ca2+]0. Salicylate probably facilitates the entry of Ca2+ into the nerve terminal or sensitizes the process that is regulated by Ca2 , thereby stimulating the release of transmitter. Surface negative charges may have an important role in the effect of [Ca22]0.

Animals

Augmentation and subsequent attenuation of Ca2+ current due to lipid peroxidation of the membrane caused by t-butyl hydroperoxide in the rabbit sinoatrial node.

Cellular electrophysiological effects of membrane lipid peroxidation by t-butyl hydroperoxide (TBH) were studied in the rabbit sinoatrial (SA) node. Superfusion for 1-5 min with 300 microM TBH caused an initial increase and subsequent decrease in the spontaneous firing frequency of the SA node. Voltage clamp experiments revealed that TBH initially enhanced but later blocked the Ca2+ current. Thus, membrane lipid peroxidation appears to accelerate and then suppress physiological automaticity by causing biphasic changes in the Ca2+ current.

Action Potentials

Fascicular parasystole associated with tachycardia-dependent right bundle branch block.

A 43-year-old female with a chief complaint of palpitation was subjected to clinical electrophysiological studies. Initial standard 12-lead ECG revealed that her palpitation was caused by fascicular parasystole firing at the basic cycle length of 1.25-1.40 seconds, and that both sinus and parasystolic beats were associated with left anterior fascicular block and tachycardia-dependent RBBB. His-bundle electrocardiogram suggested that the parasystolic focus was located in the proximal portion of the anterior fascicle of the left bundle branch and that the site of tachycardia-dependent conduction block was located in the main right bundle branch. These findings suggest that diffuse pathological changes in the intraventricular conducting system were responsible for both the conduction block and automatic impulse formation in the present case.

Adult

Rapid screening for Staphylococcus aureus infection by measuring enterotoxin B.

We developed a simple, sensitive laser nephelometric assay (LNA) to detect circulating staphylococcal enterotoxin B (SEB). This assay yields the result within 2 h and needs no special treatment. Influence of protein A, a product generated by Staphylococcus aureus, was negligible in this assay. The levels of SEB in plasma were measured in 28 patients with and without S. aureus infection with the LNA. The levels of SEB in plasma increased significantly in patients with S. aureus infection. We also demonstrated that the levels of SEB in plasma were higher in patients with methicillin-resistant S. aureus infection than in patients with nonresistant staphylococcal infection. Our data indicate that LNA is a useful assay in the early diagnosis of methicillin-resistant S. aureus infection.

Cross Reactions

Ventilatory and heart rate responses to hypoxia and hypercapnia in patients with diabetes mellitus.

The ventilatory response to isocapnic progressive hypoxia and hyperoxic progressive hypercapnia in 24 diabetic patients were compared with those of sex and age matched normal control subjects. The heart rate response to hypoxia was also measured in both groups. In diabetic patients the ventilatory and heart rate responses to hypoxia were significantly lower than those in the control group (0.10 v 0.24 l/min/% fall/m2 and 0.5 l v 1.27 beats/min/% fall respectively). The ventilatory response to hypercapnia was significantly higher (1.09 v 0.76 l/min/mm Hg/m2) in the diabetic patients. There was a significant correlation between the hypoxic ventilatory response and the heart rate response in diabetic patients (r = 0.56), but not in the control group (r = 0.28). In addition, both the ventilatory and the heart rate responses to hypoxia in diabetic patients had weak but significant correlations with the heart rate variation during deep breathing. It is concluded that the ventilatory and heart rate responses to hypoxia in diabetic patients are impaired, whereas the ventilatory response to hypercapnia is well preserved.

Adult

No effect of brain blood flow on ventilatory depression during sustained hypoxia.

Minute ventilation (VE) during sustained hypoxia is not constant but begins to decline within 10-25 min in adult humans. The decrease in brain tissue PCO2 may be related to this decline in VE, because hypoxia causes an increase in brain blood flow, thus resulting in enhanced clearance of CO2 from the brain tissue. To examine the validity of this hypothesis, we measured VE and arterial and internal jugular venous blood gases simultaneously and repeatedly in 15 healthy male volunteers during progressive and subsequent sustained isocapnic hypoxia (arterial PO2 = 45 Torr) for 20 min. It was assumed that jugular venous PCO2 was an index of brain tissue PCO2. Mean VE declined significantly from the initial (16.5 l/min) to the final phase (14.1 l/min) of sustained hypoxia (P less than 0.05). Compared with the control (50.9 Torr), jugular venous PCO2 significantly decreased to 47.4 Torr at the initial phase of hypoxia but did not differ among the phases of hypoxia (47.2 Torr for the intermediate phase and 47.7 Torr for the final phase). We classified the subjects into two groups by hypoxic ventilatory response during progressive hypoxia at the mean value. The decrease in VE during sustained hypoxia was significant in the low responders (n = 9) [13.2 (initial phase) to 9.3 l/min (final phase of hypoxia), P less than 0.01], but not in the high responders (n = 6) (20.9-21.3 l/min, NS). This finding could not be explained by the change of arterial or jugular venous gases, which did not significantly change during sustained hypoxia in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Effects of hypercapnia on brain pHi and phosphate metabolite regulation by 31P-NMR.

The ability of brain cells to regulate intracellular pH (pHi) and several phosphate metabolites was evaluated during 1 h of hypercapnia (inspiratory CO2 fraction of 0.10 and 0.05) in anesthetized rats by 31P high-field (145.6 MHz) nuclear magnetic resonance spectroscopy. Body temperature was maintained at 37 +/- 0.5 degrees C. Fully relaxed spectra were obtained for controls and 30-50 min after CO2 loading and CO2 withdrawal. Spectra were taken serially every 2.5 min after gas mixtures were changed. Brain pHi decreased 0.10 +/- 0.02 units [7.06 +/- 0.01 (SE)] to 6.96 +/- 0.01 (P less than 0.001) after 30-50 min of 10% CO2 breathing, and arterial pH decreased 0.24 +/- 0.01 units. Brain pHi decreased by 0.045 +/- 0.01 units (7.05 +/- 0.01 to 7.01 +/- 0.01, P less than 0.05) during 5% CO2 breathing. Brain pHi returned to control values after 30-50 min of CO2 washout in both groups. In three of six animals breathing 10% CO2, there was an undershoot in brain pHi by 0.07-0.09 units between 2.5 and 20 min of hypercapnia. Three animals exhibited an overshoot in pHi by 0.06-0.11 units between 7.5 and 17.5 min during CO2 washout. Phosphocreatine-to-Pi and Pi-to-beta-ATP ratios changed during hypercapnia and returned to base line after withdrawal of CO2. The findings of a smaller brain pHi change than arterial pH change and undershoots and overshoots in pHi support the view that pHi regulation involves active processes such as transmembrane ion transport.

Adenosine Triphosphate