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Biomedical subjects

S Ichikawa

Publications and source records attributed to S Ichikawa.

At least 217 records · Page 12Linked to original sources

[Clinical evaluation of imipenem/cilastatin sodium against severe infections complicating hematological disorders and solid tumors].

Imipenem/cilastatin sodium (IPM/CS) was administered to a total of 67 patients with severe infections complicating hematological disorders and solid tumors. Fifty patients are included in the present analysis of efficacy and 64 in that of safety. 1. Out of 31 patients with hematological disorders, responses were excellent in 10 patients, good in 10 patients, and the efficacy rate was 64.5%. Out of 19 patients with solid tumors, responses were excellent in 8 patients, good in 8 patients and the efficacy rate was 84.2%. 2. For patients whose responses to other antibiotics had been poor, the efficacy rate was 59.3% in the group with hematological disorders and 62.5% in the group with solid tumors. 3. The relationship between the neutrophil count and efficacy was studied in the patients with hematological disorders. The efficacy rate for 8 patients whose neutrophil counts were 500/mm3 or less was 75.0%. 4. For the patients with hematological disorders, the efficacy rate for patients from whom causative organisms were isolated was 70.0% and that for patients for whom they were unknown was 61.9%. 5. Adverse reactions were observed in 3 patients and abnormal laboratory test results in 2 patients. However, they were mild and disappeared after discontinuation of this drug. From these results, IPM/CS is considered to be a useful antibiotic for the treatment of severe infections complicating hematological disorders and solid tumors.

Adolescent↗

Multiple mRNAs of monkey tyrosine hydroxylase.

The multiplicity of tyrosine hydroxylase (TH) mRNA was examined in two species of primate, Macaca irus and Macaca fuscata, one species of insectivore, Sunkus murinus and one species of rodent, rat. To investigate the TH multiplicity, total RNAs from various species of animals were reverse transcribed and 5' portion of TH cDNAs were amplified by polymerase chain reaction. The resulted DNA fragments were analyzed by agarose gel electrophoresis. Two types of TH mRNA corresponding to type 1 and type 2 were detected in adrenal gland and brain of both species of primate. In contrast, only a single form of TH mRNA was detected in Sunkus murinus and rat.

Adrenal Glands↗

Time-related changes in plasma adrenal steroids during treatment with spironolactone in primary aldosteronism.

Time-related changes in plasma levels of aldosterone, deoxycorticosterone, corticosterone, and cortisol were studied during treatment with spironolactone in 8 patients with primary aldosteronism due to adenomas. Plasma renin activity (PRA), serum sodium and serum potassium were also measured. The patients were treated with spironolactone, 75 to 225 mg daily, and blood samples were withdrawn on days 7, 14, and 21 to 28 of drug administration. Plasma aldosterone concentrations (PAC) were not altered by spironolactone; however, significant increases were observed in plasma deoxycorticosterone on days 21 to 28 and in plasma corticosterone and cortisol on days 14 and 21 to 28. The suppressed PRA values were markedly increased on days 21 to 28 and low levels of serum potassium returned to the normal range on day 7. The lack of increase in PAC, despite a remarkable rise in PRA and serum potassium, suggests biosynthetic inhibition of spironolactone at the sites of 18-hydroxylation and/or 18-oxidation, because of the elevation of deoxycorticosterone and corticosterone.

Adenoma↗

Advantage of cine-MR imaging for the evaluation of valvular regurgitation.

It is well known that the regurgitant blood flow of valvular disease shows a low intensity signal (LS) in cine-MR imaging (cMRI). To determine the significance of cMRI in evaluation of valvular regurgitation, 104 patients who had been assessed by cineangiography also underwent oblique cMRI for mitral regurgitation (MR) and aortic regurgitation (AR), and transverse cMRI for tricuspid regurgitation (TR). In evaluating the accuracy of diagnosis of valvular regurgitation on the basis of the presence of LS in the recipient chamber, sensitivity was found to be 93.5% for MR, 100% for AR and 85.7% for TR; specificity was 76.9% for MR and 100% for AR. The length and area of LS were planimetered in any view with the largest area, and its ratios to the length and area of the recipient chamber of view were calculated. Each index was significantly higher than the degree calculated by cineangiography. The best correlation with angiography was the ratio of the area of LS to the recipient chamber, and a semiquantitative classification by the index was coincident with angiographic severity in 38 of 43 (88.4%) patients undergoing MR, and in 28 of 30 (93.3%) patients undergoing AR. Thus, cMRI is a clinically useful noninvasive method in the identification and semiquantitative assessment of regurgitation severity.

Aortic Valve Insufficiency↗

Experimental studies of the load reducing effects of nitroglycerin in heart failure.

The load-reducing effect of nitroglycerin (NTG), a vasodilator, was studied in dogs with heart failure. The chordae tendineae of the mitral valve were transected to induce acute mitral regurgitation (MR) for hemodynamic evaluation. By such surgical treatment, preload indices such as left ventricular end-diastolic pressure (LVEDP) and left atrial pressure (LAP) increased significantly, and subsequent cardiac dysfunction and heart failure were indicated by another decrease in stroke volume, myocardial contractility, forward flow, and myocardial oxygen consumption. To dogs with artificially established acute MR, 3 micrograms/kg/min of NTG was administered intra-arterially by means of a continuous infusion, that resulted in decrease of LVEDP, LAP and central venous pressure (CVP). Thus, a reduction of preload was determined. Simultaneously, afterload indices such as aortic systolic pressure (Aos), aortic mean pressure (Aom) and total peripheral resistance (TPR) decreased remarkably. Afterload reduction depended on the amount of venous return; therefore, an extra-corporeal circulation system was applied in order to supply a constant venous return before NTG administration. This caused a significant decrease in aortic diastolic pressure (Aod), Aos, Aom, left ventricular systolic pressure (LVSP) and TPR, and an increase in myocardial contractility and cardiac output. This suggested that afterload reduction might be realized by the vasodilatory effect of NTG on the resistance vessels.

Animals↗

Effects of insulin on plasma renin activity, plasma atrial natriuretic peptide and body fluid volume in diabetes mellitus.

The effects of insulin treatment on plasma renin activity (PRA), plasma atrial natriuretic peptide (ANP) and body fluid volume were studied in 16 hospitalized patients with insulin-independent diabetes mellitus. Parameters were recorded for 2 days during treatment by diet alone and for 3 weeks after starting insulin. Blood samples were obtained weekly from 9 patients for the measurement of fasting plasma glucose, hematocrit, PRA and plasma ANP. A 24-hr urine sample was collected to determine the urinary excretion of glucose and sodium. In a separate group of 7 patients, plasma volume and extracellular fluid volume were determined by the Evans blue and sodium thiocyanate dilution tests, respectively. In the group of 9 diabetic patients, significant (p less than 0.05) reductions in fasting plasma glucose, hematocrit and the urinary excretion of sodium and glucose were seen with insulin treatment. PRA fell significantly (p less than 0.05) from 5.2 +/- 1.2 ng/ml/hr (mean +/- SEM) on the control days to 2.3 +/- 0.5 on the 21st day after starting treatment. Plasma levels of ANP averaged 35 +/- 5 pg/ml on the control days and these did not change significantly. In the other group of 7 patients, both plasma volume and extracellular fluid volume increased significantly (p less than 0.05) with insulin treatment. A sodium-retaining effect of insulin and a decrease in osmotic diuresis may have increased the body fluid volume and caused the fall in PRA. Thus, a vasodilatory action of insulin may assist in compensation for the increase in body fluid volume, preventing a rise in plasma ANP levels.

Atrial Natriuretic Factor↗

Increase in hematocrit by nifedipine in hypertensive patients.

The hematocrit, hemoglobin, serum total protein and serum albumin concentration increased significantly following sublingual administration of nifedipine in patients with essential hypertension (p less than 0.05). The mean increase in hematocrit at 60 min after administration was 1.5%. The results suggest a decrease in plasma volume, perhaps due to diuresis and a shift of fluid from the intravascular to the extravascular space.

Adult↗

The intimate association of nerve terminals with the lacteal endothelium in the canine duodenal villi observed by transmission electron microscopy of serial sections.

A hitherto undescribed intimate association of the nerve fibers with the central lacteal endothelium in the canine duodenum was demonstrated by transmission electron microscopy of ultrathin serial sections. Around the proximal half of the entire extent of the central lacteal, there exist three to ten unmyelinated nerve fibers 0.1-0.15 microns in diameter. Some of these exhibit bulbar swellings (0.7-1.0 microns in diameter) which contain small clear vesicles (30-35 nm in diameter) and/or rather large vesicles (60-90 nm) with electron-dense cores (40-60 nm). Most of the bulbar structures of the nerve fibers are in contact with or surrounded by the central lacteal endothelial cells. These results suggest the existence of a neuronal control over the activity of the lacteal endothelial cells.

Animals↗

Azidothymidine inhibition of thymidine kinase and synergistic cytotoxicity with methotrexate and 5-fluorouracil in rat hepatoma and human colon cancer cells.

Azidothymidine (AZT, 3'-azido-3'-deoxythymidine, zidovudine) competitively inhibited the activity of thymidine kinase (EC 2.7.1.21) in extracts of rat hepatoma and sarcoma cells; Dixon plots yielded a Ki = 1-2 microM. Azidothymidine (100 microM) exerted synergistic cytotoxicity with methotrexate (0.05 microM) in hepatoma cells in culture in clonogenic assay. Thymidine (50 microM) counteracted the effect of azidothymidine and prevented synergistic action. Azidothymidine (10 microM) was synergistically cytotoxic with 5-fluorouracil (0.3 and 0.5 microM) in HT-29 human colon carcinoma cells. Thymidine (10 microM) abolished synergism. These studies suggest a new role for azidothymidine which, as an inhibitor of thymidine salvage, should enhance synergistically the clinical anticancer impact of blockers of de novo biosynthesis of thymidylates (methotrexate, 5-fluorouracil).

Animals↗

[Studies on acetylspiramycin. II. Biological activities of spiramycin components].

Acetylspiramycin (ASPM) was fractionated using high performance liquid chromatography (HPLC). The peak fractions were named F1 to F7 successively in order of increasing retention times (Rt), i.e., increasing hydrophobicity, and studied for 1) antibacterial activities (MIC), 2) antibacterial potency against Bacillus subtilis ATCC 6633, 3) therapeutic effect on mice infected with Streptococcus pneumoniae III, Staphylococcus aureus Smith, 4) acute toxicity by i.p. administration to mice (LD50) and 5) cytotoxicities to fibroblasts derived from Chinese-hamster lung (CHL), cow pulmonary artery endothelial cells (CPAE) and rat hepatic cells. The results obtained are summarized below. 1. Components F1 and 4'-acetylspiramycin F2 had significantly different biological activities from those of other components: F1 showed the lowest antibacterial potency of 492 micrograms (potency)/mg, F2 showed the highest antibacterial potency of 2,040 micrograms (potency)/mg and correspondingly the lowest LD50 value of 692 mg/kg (the highest toxicity). The therapeutic effect of F2 on infections in mice was found to be the second smallest and was superior only to that of F1. The LD50 value of F1 was 1,200 mg/kg and similar to that of ASPM. 2. Antibacterial potencies of F3, F4, F5 and F6 were 1,165, 1,266, 1,374 and 1,530 micrograms (potency)/mg, respectively; fraction with the higher antibacterial activities corresponded to the longer retention times, i.e., the greater hydrophobicities. The most hydrophobic component, F7, 3-propionyl-3",4"-diacetylspiramycin, however, showed a low antibacterial potency of 1,085 micrograms (potency)/mg, next to the lowest one, F1, a fact which was in contradiction to with the sequential relation between hydrophobicities and potencies from F3 to F6.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Studies on so-called "postoperative erythroderma": report of four cases].

"Postoperative erythroderma", the pathogenesis of this disease have solved as graft-versus-host disease (GVHD) due to blood transfusion, is fatal and impossible to cure for the time being. Therefore the prevention against the disease is very important. One woman and three men who underwent an operation and blood transfusion at our department died of this disease. They fell into high fever on 11-13 days, erythroderma on 12-16 days, liver dysfunction on 14 days, and leukocytopenia on 17-19 days, after surgery and transfusion. Eventually, they all suffered from thrombocytopenia, diarrhea, renal dysfunction, and sepsis which led to death. The clinical course, macroscopic and microscopic findings of them coincided with those of GVHD. Since 1989, we have tried following methods for prevention of postoperative erythroderma: Reducing blood transfusion, especially fresh blood and fresh thrombocyte plasma, by using predeposited autologous blood, autologous washed erythrocytes collected from the operative area before and after extracorporeal circulation (ECC), concentrated residual blood from the ECC using a hemoconcentrater, and 1,500 rad of cobalt-irradiation of fresh blood, fresh thrombocyte plasma, and blood collected within 7 days prior to the transfusion. Postoperative erythroderma has not been experienced by introduction of these methods since 1989.

Aged↗

[The effect of smoking and drinking habit on the process from liver cirrhosis to liver cancer].

A retrospective cohort study of liver cirrhosis cases was carried out. 270 cases of liver cirrhosis which were confirmed histologically from 1972 to 1981 at Juntendo University Hospital, were followed up until the end of 1988. The average observation period for these cases was 74 months or 6.2 years, and we found 141 death cases including 46 of primary liver cancer (PLC). The analysis of survival rate revealed that the smoking group had a slightly higher death rate of PLC than non-smokers, and the ex-smoker group had a much higher survival rate than the continuous smoking group. On the other hand, it was found that the alcohol-drinking group had a much lower death rate of PLC than the non-drinkers group, and that there was no difference of the survival rate among drinkers, non-drinkers and ex-drinkers.

Adult↗

Molecular cloning and expression of ribosome releasing factor.

Ribosome releasing factor (RRF) is responsible for the release of ribosomes from messenger RNA at the termination of Escherichia coli protein biosynthesis (Hirashima, A., and Kaji, A. (1972) Biochemistry 11, 4037-4044). RRF has been partially analyzed by Edman degradation to obtain its amino acid sequence. Based on this analysis, a 47-nucleotide probe was synthesized and used to screen clones from the Clarke and Carbon Gene Bank which carry sequences within the 0-10 min region of the E. coli gene map. The entire RRF cistron was detected on the plasmid pLC6-32. The DNA sequence of RRF was determined, and it was deduced that RRF consists of 185 amino acids with a calculated molecular weight of 20,639. A rho-independent transcriptional termination sequence was found immediately downstream of the RRF cistron. The RRF gene was subcloned into the vector pUC19, and the resulting plasmid was named pRR1. E. coli harboring this plasmid expressed much more RRF than cells containing pUC19, and it was biologically active.

Amino Acid Sequence↗

Localization of the ribosome-releasing factor gene in the Escherichia coli chromosome.

The ribosome-releasing factor (RRF) gene was localized at a position between 2 and 6 min on the Escherichia coli chromosome by measuring the gene-dosage-dependent production of RRF in various E. coli F' merozygotes. This position was confirmed and refined by using a nucleotide probe corresponding to a 16-amino-acid sequence in RRF. It was found that the RRF gene was contained in pLC 6-32 of the Clark-Carbon Gene Bank. Restriction enzyme mapping of E. coli genomic DNA with the above probe led us to conclude that the RRF gene is situated in the 4-min region, somewhere downstream (clockwise) of the elongation factor Ts gene, tsf. A pLC 6-32-derived DNA fragment which carries the RRF gene was found to contain a partial sequence of tsf. The exact location of the translational initiation site of the RRF gene was determined to be 1.1 kilobases downstream from the translational termination site of tsf. The RRF gene is designated frr.

Amino Acid Sequence↗

[Effect of partial nephrectomy on calyceal and pelvic peristalsis in the isolated pig kidney].

Ureteral peristalsis begins at the border between the major calyces and their minor calyces in the multicalyceal kidneys like those in the pig and human. The urologists often perform partial nephrectomy. But there has been no report on the impairment of calyceal and pelvic peristalsic function after partial nephrectomy. Therefore the objective of this study was to explore experimentally the effect of partial nephrectomy on the calyceal and pelvic peristalsis by electroomyographic tracing from the renal calyces, pelvis and ureter in isolated pig kidneys after successive resection of major calyces. Calyceal and pelvic peristalsis remained normal under the control of calyceal pacemaker as long as at least one of the upper, middle and lower major calyces of isolated pig kidney is intact. The observed facts suggest importance of the calyceal system as a pacemaker for maintaining normal ureteral peristalsis.

Animals↗