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Biomedical subjects

M Nishimura

Publications and source records attributed to M Nishimura.

At least 901 records · Page 50Linked to original sources

Blockade of Na+ current by promethazine in guinea-pig ventricular myocytes.

1. To elucidate the antiarrhythmic mechanism of promethazine, its effects on the fast Na+ current (INa) were examined in single guinea-pig ventricular myocytes by whole-cell voltage clamp methods. 2. Promethazine blocked INa with a KD of 42.6 microM and Hill's coefficient of 1.1 at a holding potential of -140 mV. 3. The INa blockade was enhanced at a less negative holding potential of -80 mV with a change of KD to 4.4 microM. Although 10 microM promethazine did not change the inactivation time constants of INa, it shifted the steady-state inactivation curve (h infinity curve) toward more negative potentials by 19.5 mV with the slope factor unaffected. 4. Double pulse experiments revealed that the development of blockade followed two-exponential functions having time constants of 7 and 220 ms at -20 mV. 5. Promethazine slowed the repriming of INa. This was associated with the development of slow phase having a time constant of 1160 +/- 59 ms. 6. Promethazine produced a profound use-dependent block when the cell was repeatedly stimulated with interpulse intervals shorter than 1 s. However, short pulses of 2 ms duration hardly produced such a use-dependent block. Hence, open channel blockade is considered to play a minor role in the promethazine action on INa. 7. These results suggest that promethazine blocks cardiac INa in a manner similar to class I antiarrhythmic drugs and that this effect may account for its antiarrhythmic action.

Algorithms↗

[A clinical study on postantibiotic effect (PAE) and its application to chemotherapy for complicated cystitis with an automatic simulator of urinary drug concentration].

In an in vitro complicated cystitis model, the concentrations of the urinary antimicrobial agents were determined using a computer-controlled automatic urine concentration simulator. The effects on the bacterial count curves showing the presence or absence of PAE in antimicrobial agents were studied by comparing the times required for regrowth to the concentration at the initial inoculation, i.e., effective regrowth time (ERT). The following results were obtained. 1. When beta-lactam antimicrobial agents (such as AMPC and CFIX) with no PAE against the gram-negative rods were tested, the ERT of the gram-negative rods were about two hours shorter than that of the gram-positive coccus. 2. When new quinolone antimicrobial agents (such as OFLX) and aminoglycosides (such as ISP) that possess PAE against both the gram-positive and negative organisms were used there was no difference between ERT of the gram-negative rods and gram-positive coccus. Therefore, it was demonstrated that the presence or absence of PAE is also reflected in the cell number curve in the case of this in vitro model, more closely related to clinical cases, when the antibiotics is simulated in urinary concentration shifting.

Amoxicillin↗

[Clinical efficacy of levofloxacin (LVFX) single-dose therapy in female acute uncomplicated cystitis].

Treatment of infections by the use of antimicrobial agents should be made essentially in a dose close to the minimally required dose. Acute uncomplicated cystitis in female fits as the subject for a single-dose therapy since it is an infection reactive relatively easily to antimicrobial agents. Accordingly, an assessment has been made regarding the therapeutic results of the single-dose therapy in 76 female cases of acute uncomplicated cystitis by the use of LVFX 200 mg which is a new quinolone. The urinary concentration more than MIC90 to Escherichia coli is sustained for about 3 days by this single-dose therapy. As a result of judging the therapeutic results from the reactions of the three clinical findings of pain on micturition, pyuria and bacteriuria, excellent therapeutic results were obtained with effective rates being 100% (76/76) on the day 3, 93.9% (46/49) on the day 7 and 94.4% (34/36) on the day 14. The rate of cystitic symptoms which recurred posed no problem, being 12.5% (5/40) up to three months, as investigated by a questionnaire. As a result of performing close urological examinations such as cystoscopy on six cases with insufficient results or recurrence, we could detect mild underlying conditions which are considered to be intractable factors in the bladder in three cases. From the above results, the single-dose therapy of acute uncomplicated cystitis in the female by LVFX which is a new quinolone was considered to be an excellent therapeutic drug from its characteristics such as its therapeutic results being the same as the conventional therapy by daily administration, excellent drug compliance, low cost, hard selectiveness of resistant strains, less side effects and furthermore it gives the opportunity of detecting a latent and mild underlying condition.

Acute Disease↗

[Significance of the combined treatment with isepamicin and piperacillin in an in vitro model for complicated cystitis operated by automatic simulator apparatus for urinary concentration].

Isepamicin (ISP) and piperacillin (PIPC) were shifted to the urinary concentration by employing an in vitro complicated cystitis model operated by a computer-controlled automatic simulator for urinary concentration, and administrated to bacteria in the urinary bladder model (Pseudomonas aeruginosa: P. aeruginosa, initial cell concentration: 10(7) cfu/ml). In this case, effects by single treatment with ISP or PIPC on cell number curves were examined. Further, significance of the combined treatment with ISP and PIPC were investigated by changing the order of each treatment. And following the results were obtained. 1. In a single treatment with PIPC the cell concentration was minimum (10(4) cfu/ml) at 9th hour after its treatment and thereafter, regrowth to the same level as the initial concentration was observed at 16th hour. 2. In the case of single treatment with ISP, the cell concentration became minimum (10(2) cfu/ml) at 13th hour after the treatment and raised to the same concentration as the initial one at 25th hour. 3. In the combined treatment, the cell concentration was minimum (less than 10(1) cfu/ml) at 26th hour in the case of prior treatment with ISP. Thereafter, regrowth was observed and the cell concentration at 42nd hour reached to the initial cell concentration. 4. In simultaneous treatment with ISP and PIPC, the cell concentration at 24th hour was minimum (10(1) cfu/ml) and reached to the same level as the initial one after regrowth. From these results, it was found that the combined treatment with ISP and PIPC caused more reduction of the cell concentration than either single treatment. Further, regrowth of the cells was suppressed for longer duration.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer Simulation↗

[Epidemiological and bacteriological study on gonococcal infections].

Epidemiological and bacteriological studies on Neisseria gonorrhoeae isolated in Sapporo, Japan, in 1980 and 1991 performed and the following results were obtained. 1. The range of age in the patients infected with Neisseria gonorrhoeae tended to be younger than those in the whole country. 2. Male patients in the early 20s or younger with gonococcal urethritis were often infected by bon-professional females but those in their late 20s or older were often infected from professional females, for example prostitutes and hostesses. 3. The rate of professional females who were positive to gonococci reached 17.4% and young females in their teens with cervicitis had the highest morbidity rate of gonococci than those in the older females. 4. The latent period in gonococcal infections tended to become longer gradually. 5. The isolation rate of penicillinase producing Neisseria gonorrhoeae (PPNG) showed a peak of 23.9% (61/255) in 1985, but gradually declined thereafter and it was 3.7% (1/27) in 1991. 6. An investigation on auxotype showed a decline of proto and Pro-strains and an increase of AHU-strains in non-PPNG. And most of the PPNG belonged to proto or Pro-strains. 7. With the relationship between auxotype and sensitivity to AMPC, AHU-strains were more sensitive than proto or Pro-strains.

Adolescent↗

Identification of membrane antigen C33 recognized by monoclonal antibodies inhibitory to human T-cell leukemia virus type 1 (HTLV-1)-induced syncytium formation: altered glycosylation of C33 antigen in HTLV-1-positive T cells.

We isolated four monoclonal antibodies (MAbs), M38, M101, M104, and C33, which were capable of inhibiting syncytium formation induced in a human T-cell line, MOLT-4-#8, by coculture with human T-cell leukemia virus type 1 (HTLV-1)-positive human T-cell lines. The MAbs had, however, no inhibitory activity on syncytium formation induced in a human osteosarcoma line, HOS, by HTLV-1-positive T-cell lines. They also did not inhibit syncytium formation induced in MOLT-4-#8 by human immunodeficiency virus type 1-positive MOLT-4. All MAbs reacted with various human cell lines of lymphoid and nonlymphoid origins, including HTLV-1-positive T-cell lines. Furthermore, they all reacted with a murine A9 clone containing human chromosome 11 fragment q23-pter. Two MAbs, M104 and C33, immunoprecipitated a membrane antigen with the same molecular size. The antigen (henceforth called C33 antigen) was about 40 to 55 kDa in HTLV-1-negative Jurkat, CEM, MOLT-4, and normal peripheral blood CD4-positive human T cells and about 40 to 75 kDa in HTLV-1-positive C91/PL, TCL-Kan, MT-2, and in fresh HTLV-1-transformed CD4-positive human T-cell lines. Pulse-chase experiments revealed that C33 antigen was synthesized as a 35-kDa precursor that was then processed to 41 to 50 kDa in MOLT-4 and to 44 to 70 kDa in C91/PL. In the presence of tunicamycin, a 28-kDa protein was synthesized. The conversion from 35 kDa to 41 to 50 kDa in MOLT-4 and to 44 to 70 kDa in C91/PL was inhibited by monensin. Treatment with N-glycanase alone, but not with sialidase and O-glycanase in combination, completely removed the sugar moiety of C33 antigen from both HTLV-1-negative Jurkat and HTLV-1-positive C91/PL. Therefore, C33 antigen has only N-linked carbohydrates, the modification of which appears to be substantially altered in the presence of the HTLV-1 genome.

Antibodies, Monoclonal↗

Effect of aminophylline on brain tissue oxygenation in patients with chronic obstructive lung disease.

BACKGROUND: It is known that theophylline reduces cerebral blood flow in humans. To quantitatively assess the possible adverse effect of theophylline on brain tissue oxygen tension (PO2) due to decreased cerebral blood flow, two sets of experiments were conducted in mildly hypoxaemic patients with chronic obstructive lung disease. METHODS: Firstly, internal jugular venous PO2 (PjO2) was measured simultaneously with arterial and mixed venous blood PO2 (PaO2 and PvO2) during right heart catheterisation in 10 subjects (mean PaO2 73 mm Hg; conversion factor: 10 mm Hg = 1.33 kPa)) before and after intravenous infusion of aminophylline (6 mg/kg). The PjO2 and PvO2 were considered to reflect the average tissue PO2 for the brain and for the whole body respectively. Secondly, the relation between PaO2 and PjO2 over a wide range, with the PaCO2 similar to that in the first study, was investigated in a different group of 12 subjects by stepwise changes in inspiratory gas composition. RESULTS: The mean PjO2 decreased by as much as 6 mm Hg 15 minutes after an infusion of aminophylline, whereas PaO2 stayed at the same level and PvO2 showed only a small decrease. The low PjO2 value of 29 (SD 6) mm Hg with aminophylline in the first study was similar to the PjO2 value of 30 (2) mm Hg obtained during severe hypoxia (PaO2 45 mm Hg) in the second study. The coefficient of oxygen delivery for the brain decreased by 29% with aminophylline treatment, but did not change significantly during severe hypoxic challenge. CONCLUSIONS: These data suggest that an infusion of aminophylline lowers brain tissue PO2 appreciably when given to mildly hypoxaemic patients with chronic obstructive lung disease.

Aminophylline↗

Rigid spine syndrome with selective respiratory muscle weakness.

Rigid spine syndrome is a rare myopathy characterized by mild axial and proximal muscle weakness, limitation of neck and trunk flexion, scoliosis and mild joint contractures. We describe a 20-year-old woman with this syndrome who developed severe respiratory muscle failure disproportionate to the well-preserved extremity muscles. Nocturnal home care ventilation has completely restored her arterial oxygen desaturation during a 5-year follow-up.

Adult↗

Tissue renin-angiotensin systems in renal hypertension.

Angiotensinogen messenger RNA (mRNA) levels were measured in the brain (hypothalamus, lower brain stem, cerebellum), liver, kidneys, and adrenal glands of rats made hypertensive by ligation of the aorta between the renal arteries. We also measured renin mRNA in the kidneys of these renal hypertensive rats. The early phase of hypertension (day 6) was associated with significant increases in plasma renin activity and levels of circulating angiotensin II. The circulating renin-angiotensin system was not activated in the later phase of hypertension (day 24). Angiotensinogen mRNA levels were elevated in the lower brain stem of hypertensive rats at both stages of hypertension. In contrast, angiotensinogen mRNA levels in the hypothalamus were increased only at day 6 after aortic ligation. Decreased levels of angiotensinogen mRNA were observed in the cerebellum in both the early and later phases of the hypertension. Angiotensinogen mRNA levels in the adrenal gland below the ligature fell in the early phases but rose in the later phases of hypertension. Renin mRNA levels of the ischemic kidney remained elevated at both the early and later phases, whereas in both ischemic and nonischemic kidneys, levels of angiotensinogen mRNA remained below sham values throughout the period of study. These results indicate differential expression of renin-angiotensin system mRNAs in tissues of renal hypertensive rats. The differential changes in the expression of angiotensinogen mRNA over the course of development and maintenance of renal hypertension suggest that factors in addition to angiotensin II are important in modulating the expression of renin-angiotensin system genes.

Adrenal Glands↗

Augmented heart rate response to hypoxia in patients with chronic obstructive pulmonary disease.

Effects of acute, progressive isocapnic hypoxia on heart rate (HR) and ventilation were determined in 31 patients with chronic obstructive pulmonary disease (COPD) and in 24 normal control subjects. There was an inverse linear relationship between heart rate and SaO2 in each subject. The slope factor (delta HR/delta SaO2) obtained from the regression line was significantly higher in the patients with COPD than in the normal control subjects (0.888 +/- 0.309 SD beats/min/% fall in SaO2 versus 0.693 +/- 0.287; p less than 0.05), whereas the ventilatory response (delta VE/delta SaO2) was not significantly different between the two groups. To elucidate factors responsible for the augmented heart rate response to hypoxia in the patients with COPD, we examined the relationships of delta HR/delta SaO2 with age, physical characteristics, pulmonary function data, and arterial blood gas data in all the subjects. A weak but significant relationship was found only between delta HR/delta SaO2 and FEV1/VC, %FEV1, RV/TLC, and %RV. Because the HR response to hypoxia correlates only with parameters that reflect the grade of airway obstruction, we believe that the enhanced HR response seen in patients with COPD is a result of the disease process in the airway and tissue, although the precise mechanism was not specified in this study.

Female↗

Antihypertensive and metabolic effects of long-term treatment with amosulalol in non-insulin dependent diabetics.

In this open study, 41 hypertensive patients with non-insulin dependent diabetes mellitus were treated with the combined alpha- and beta-adrenoceptor blocker amosulalol hydrochloride for 24 weeks, either alone or added to existing antihypertensive therapy. The effects on blood pressure, glucose and lipid metabolism were examined. Daily administration of 20 to 60 mg amosulalol caused a significant reduction in both systolic and diastolic blood pressure within 2 weeks. This effect was stable, lasting for the entire trial period. The mean systolic and diastolic blood pressure decreased from 174 +/- 13/92 +/- 9 mmHg at the beginning to 148 +/- 16/80 +/- 11 mmHg at the end of the trial. Heart rate was not affected. Plasma glucose and haemoglobin Alc levels showed a tendency to decrease without any statistical significance. Total and HDL-cholesterol and triglyceride levels also remained unchanged. Although 3 patients had complained of dizziness, all were easily manageable. The results indicate that amosulalol is effective in the treatment of hypertension in non-insulin dependent diabetics and does not affect glucose and lipid metabolism.

Adult↗

Beta-3 adrenergic agonist, BRL-26830A, and alpha/beta blocker, arotinolol, markedly increase regional blood flow in the brown adipose tissue in anesthetized rats.

Regional vascular effects of some adrenergic agents, focussing on brown adipose tissue (BAT), were investigated using tracer microspheres with a reference sample method in the anesthetized rat. Intravenous injections of 0.5 mg/kg BRL-26830A, a beta 3-adrenergic agonist, increased heart rate, but changes in blood pressure and cardiac output were not significant. The drug decreased blood flow in the brain, the spleen and the kidneys, but markedly increased it in BAT. At 2 mg/kg, arotinolol, an alpha/beta-adrenergic blocker, decreased blood pressure by 20 mmHg and increased cardiac output by 95 ml/min/kg. It slightly but significantly decreased blood flow in the liver and the spleen, but markedly increased the flow in BAT. Acebutolol, a beta 1-adrenergic blocker, decreased blood flow in the liver, the spleen, the pancreas, the kidneys, the adrenals, the skeletal muscle and the skin. Bunazosin, an alpha 1-adrenergic blocker, decreased it in all organs and tissue expect the brain and BAT. The pattern of redistribution of blood flow by arotinolol was very similar to that caused by BRL-26830A. Acebutolol and bunazosin rather decreased the blood flow in the BAT. These results indicate that stimulation of beta 3-adrenergic receptors, in BAT results in vasodilation, and that arotinolol may bind to those beta 3-adrenergic receptors.

Adipose Tissue, Brown↗

Compensatory changes in silver-stainability of nucleolar organizer regions in mice.

Silver-stainability of nucleolar organizer regions (NORs) that contain genes for ribosomal RNA (rDNA) was investigated using two mouse strains, BALB/cCrSlc and MOA, and their hybrid progeny. The patterns of segregation of the rDNA clusters were analyzed in terms of chromosomal C-banding and by use of a polymorphic probe for the variable region in backcrossed N2 and N3 individuals. The results indicate that the intensity of Ag-NOR staining is stably inherited in most of the rDNA clusters, irrespective of different genetic backgrounds. In some clusters, such as those on chromosome 12 of BALB/cCrSlc, a modulation of the intensity is observed. This modulation seems to be due to compensatory activation via a change in the number of actively transcribed genes. The change from silver-negative to silver-positive staining of the NOR of chromosome 12 of BALB/cCrSlc was correlated with demethylation of the genes.

Animals↗

Hypoplastic left heart syndrome associated with congenital right-sided diaphragmatic hernia and omphalocele.

Congenital diaphragmatic hernia (CDH) is associated with a variety of cardiac anomalies. However, its association with hypoplastic left heart syndrome (HLHS) is rare. We treated a female newborn with CDH, HLHS, and omphalocele. The operation for omphalocele and the diaphragmatic defect was successful, although the patient died of cardiac failure after Norwood's operation for HLHS. To our knowledge, this is the first reported case with a combination of these three major anomalies: CDH, HLHS, and omphalocele.

Female↗

Capnometry during high-frequency oscillatory ventilation.

We used capnometry during high-frequency oscillatory ventilation (HFOV), and compared CO2 measurements at the distal and proximal ends of an endotracheal tube with arterial CO2 values. Ten white rabbits (mean weight, 2.00 +/- 0.2 [SD] kg) underwent tracheostomy under anesthesia with pentobarbital. The trachea was intubated with an endotracheal tube with a second lumen for sampling respiratory gas at the distal tip. Capnometry was performed through the lumen (CO2d) and the proximal end of the endotracheal tube (CO2p). The internal carotid artery was cannulated to sample blood for measuring arterial blood gases. The differences between CO2d, CO2p, and PaCO2 were measured. Only the relation between CO2d and PaCO2 was good (r = 0.915). We concluded that capnometry can be used during HFOV to estimate PaCO2 provided that respiratory gas is sampled from the distal tip of the endotracheal tube.

Animals↗

Paradoxical bradycardia during exercise and hypoxic exposure. The possible direct effect of hypoxia on sinoatrial node activity in humans.

We describe a patient with pulmonary emphysema who developed paradoxical cardiodeceleration not only during incremental exercise associated with hypoxemia but also during progressive hypoxic challenge. Since coronary angiogram revealed no abnormality, this unique phenomenon seemed to be due to the direct effect of hypoxia on the sinus node activity.

Bradycardia↗

Colliding malignant lymphoma and adenocarcinoma of the stomach: case report.

We report a case of malignant lymphoma presenting as the superior vena cava syndrome. This case is very interesting since both adenocarcinoma mucocellulare scirrhosum, Borrman type IV, and lymphoma were present in the stomach, forming colliding neoplasms. Rather than systemically disseminated, the lymphoma cells were localized in the stomach, the intestine, a few perigastric lymph nodes and in a mediastinal mass, which may have constituted a neoplastic thymus invaded by lymphoma cells from the stomach. The unique occurrence of the histological combination as gastric colliding neoplasms is discussed.

Adenocarcinoma↗

Platelet-derived growth factor gene expression in the kidney of malignant hypertension.

To examine the pathogenetic role of platelet-derived growth factor (PDGF) in hypertensive kidney damage, we studied the gene expression of PDGF A-chain and B-chain in an animal model of malignant hypertension. Experimental malignant hypertension induced by unilateral nephrectomy combined with deoxycorticosterone and salt loading in the spontaneously hypertensive rat resulted in severely elevated blood pressure and renal histological damage, characterized by necrotizing vasculitis. Using reverse transcription-polymerase chain reaction analysis followed by Southern blot analysis, we observed that PDGF B-chain gene expression was increased in the kidney of experimental malignant hypertension and was correlated with the severity of glomerular damage, while PDGF A-chain gene expression was unaffected. Antihypertensive treatment with manidipine reduced glomerular damage and a decreased gene expression of PDGF B-chain. These results suggest that PDGF B-chain may have a role in mediating hypertensive kidney damage.

Animals↗