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Biomedical subjects

R Kojima

Publications and source records attributed to R Kojima.

At least 73 records · Page 4Linked to original sources

Studies on the nephrotoxicity of aminoglycoside antibiotics and protection from these effects (6): A mechanism for the suppressive action of latamoxef on intrarenal tobramycin level.

The mechanism by which latamoxef (LMOX) reduces intrarenal tobramycin (TOB) levels was studied. When TOB (90 mg/kg/day, s.c.) and LMOX (500 or 2000 mg/kg/day, s.c.) were given simultaneously at separate sites to rats, 20 to 30% reductions in intrarenal TOB concentration were found on the 1st and 3rd days, as compared with the results from using TOB alone. The treatment with the reaction mixture of TOB and LMOX, which was preincubated for 3 hr at 37 degrees C to form the complex of TOB and LMOX, resulted in a greater suppression of TOB level in the kidney than administration of TOB and LMOX concomitantly at separate sites. When LMOX was given to rats 0.5 or 1.5 hr before s.c. injection of TOB, there were significant reductions in intrarenal TOB concentration. However, treatment with LMOX 5 hr before, as well as 1.5 or 5 hr after TOB injection, was ineffective in reducing the accumulation of TOB in the kidney. In the rats given both drugs simultaneously, the urinary excretion pattern of TOB almost overlapped with that of LMOX. Additionally, we detected a complex of TOB and LMOX in the urine of rats given both drugs simultaneously. These results suggest that the suppressive action of LMOX on intrarenal TOB level is due to the interaction of TOB and LMOX.

Animals↗

Studies on the nephrotoxicity of aminoglycoside antibiotics and protection from these effects (9): Protective effect of inositol hexasulfate against tobramycin-induced nephrotoxicity.

We examined the protective effect of inositol hexasulfate (IS6) against tobramycin (TOB)-induced nephrotoxicity. In the electrophoretic analysis, TOB alone and IS6 alone were observed as single spots on the cathode and anode sides, respectively. However, in the mixture of TOB and IS6 preincubated at 37 degrees C for 3 hr, the tailing of the spots of TOB and IS6 were observed from the origin to the cathode and the anode sides, respectively, and the overlapping of the spots of TOB and IS6 was recognized at the origin. These results indicated that TOB directly interacted with IS6 in vitro. Assay of TOB binding to rat kidney brush border membranes (BBMs) indicated that IS6 inhibited the binding of TOB to BBMs through an interaction of TOB and IS6. No significant reduction in intrarenal TOB level was observed in the rats given TOB (90 mg/kg, s.c.) and IS6 (153 or 610 mg/kg, s.c.). However, the treatment of rats with a combination of TOB and IS6 reduced the degree of necrosis of renal tubular cells and also suppressed the increases in urinary protein, urinary enzyme activities, blood urea nitrogen and plasma creatinine induced by TOB. Additionally, we detected a complex of TOB and IS6 in the urine of rats given both compounds simultaneously. These results indicate that IS6 protects against TOB-induced nephrotoxicity and that the protective action of IS6 may be due to the inhibition of TOB binding to BBMs through an interaction of TOB with IS6.

Animals↗

Mechanical properties of hydroxyapatite-reinforced gelatin as a model system of bone.

The elastic Young's modulus of hydroxyapatite-reinforced gelatin as a mechanical model system of bone was measured as a function of the volume fraction of hydroxyapatite, phi h. Initially, the Young's modulus gradually increased with an increase in phi h and then increased rapidly in the vicinity of phi h approximately 0.2. The phi h dependence of the Young's modulus was analysed by means of the theory of composite materials. It was found that with the increase in phi h the initial uniform stress deformation mode of the sample changed to the uniform strain deformation mode. The non-linear character in phi h dependence of the Young's modulus of this system was considered to reproduce well the novel behaviour of the mechanical properties of bone as a function of the mineral fraction. The situation was considered to be similar to a percolation problem. A preliminary analysis revealed that the critical exponent about the viscosity of the system accorded with the theoretically expected value. The result may present the evidence that the discontinuous point in mechanical properties of bone would be originated from an interaction such as a percolation of mineral particles on a matrix protein.

Biomechanical Phenomena↗

Preoperative computed tomography staging of rectal carcinoma.

Pelvic computed tomography (CT) was analyzed in 48 patients with rectal carcinoma. Air was insufflated into the rectum before CT scanning. The areas of tumor (T) and rectosigmoid lumen (L) were determined for T/L ratio. Changes of the perirectal fatty tissues on CT were classified into five patterns: shaggy, granular, linear, clubbed, and wavy appearances. The T/L ratio and changes of the perirectal fatty tissue were correlated with transmural tumor extension. When the T/L ratio was above 1, tumors were frequently classified as Dukes' staging B and C, whereas a T/L ratio above 2 suggested Dukes' C classification. Clubbed or wavy appearance in the perirectal fatty tissues suggested that the tumor extended beyond the submucosa involving the muscularis propria. These findings were very useful for surgery.

Adipose Tissue↗

Chronic cervical cord compression: clinical significance of increased signal intensity on MR images.

Magnetic resonance (MR) imaging was performed in 668 patients with chronic compressive lesions of the cervical spinal canal. High signal intensity was observed within the spinal cord on T2-weighted or proton density spin-echo images in 99 patients (14.8%). Frequency of this finding was directly proportional to severity of clinical myelopathy and degree of spinal canal compression seen on MR images. Patients with a high-signal-intensity area responded less favorably than those without to surgical or medical treatment. More than 60% of the patients had this finding when grade of myelopathy or degree of canal compression was moderate to marked. Among 10 patients who received contrast material during MR imaging, one patient had definite enhancement and another had questionable enhancement in the high-signal-intensity area. The finding disappeared after decompressive surgery and medical treatment in some cases: Three of four of the patients who underwent surgery showed good clinical improvement. High signal intensity of the spinal cord produced by compressive lesions appears to be an important indicator for predicting prognosis.

Adolescent↗

Effect of dietary alpha-linolenate/linoleate balance on collagen-induced platelet aggregation and serotonin release in rats.

Male Sprague-Dawley rats at 3 weeks of age were weaned to a diet supplemented either with perilla seed oil [alpha-linolenic acid (alpha-LnA)/linoleic acid (LA) = 3.66] or with safflower seed oil (alpha-LnA/LA less than 0.01) for 5-6 weeks. The eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio in platelet phospholipids was much higher in the perilla oil group than in the safflower oil group. Platelet aggregability determined turbidometrically varied greatly among individual animals, and the difference in platelet aggregability between the two dietary groups was relatively small when higher concentrations (15 and 20 micrograms/ml) of collagen were used. However, when platelet aggregability was determined as an all-or-none phenomenon at lower concentrations (7.5 and 10 micrograms/ml) of collagen, a very distinct difference was observed between the two dietary groups; aggregability was much lower in the perilla oil group than in the safflower oil group. Collagen-induced serotonin release from platelets was significantly reduced in the perilla oil group as compared with the safflower oil group. These results emphasize the importance of estimating aggregability at threshold concentrations of collagen and confirm that dietary manipulation of the essential fatty acid balance could be useful in reducing the thrombotic tendency.

Animals↗

Studies on the nephrotoxicity of aminoglycoside antibiotics and protection from these effects (7): Effect of latamoxef on binding of tobramycin to brush border membranes isolated from rat kidney cortex.

We investigated the effect of latamoxef (LMOX) on the binding of tobramycin (TOB) to brush border membranes (BBMs) isolated from rat kidney cortex by calcium precipitation. The simultaneous treatment with TOB (0.2 mM) and LMOX (10 and 20 mM) to the BBMs fraction (about 250 micrograms protein) significantly inhibited the binding of TOB to BBMs. The addition of the reaction mixture of TOB (0.2 mM) and LMOX (4, 10 and 20 mM) which was preincubated for 3 hr at 37 degrees C, to the BBMs fraction resulted in less binding of TOB to the membranes than that observed in the case of simultaneous treatment with both drugs. Although [14C]-labeled LMOX was taken up by BBMs temperature- and time-dependently, the pretreatment with LMOX showed no obvious differences in inhibition of the TOB binding to BBMs, as compared with the result from simultaneous treatment with both drugs. Additionally, the binding of TOB to the LMOX-treated BBMs that were resuspended in fresh medium after the pretreatment with LMOX for 10 min at 37 degrees C was similar to that of TOB to the non-treated BBMs. These results indicate that LMOX inhibits the binding of TOB to BBMs not by binding to BBMs but by interacting with TOB.

Animals↗

[Studies on initiation and progression of focal glomerular sclerosis in rats].

In order to clarify the mechanisms of the initiation and progression of focal glomerular sclerosis (FGS), we investigated changes in the mesangial function or qualitative changes in the extracellular matrix of mesangium in puromycin aminonucleoside (PAN)-induced FGS in rats. At first, we investigated that the relationship between the progression of FGS and mesangial function. In order to evaluate the mesangial function, rats received the i.v. injection of colloidal carbon (C. C.) (20 or 30 mg/100 g). Results obtained from this experiment suggest that the progression of glomerular sclerosis may be related to changes in mesangial function. Furthermore, results suggest that the abnormality of the extracellular matrix may lead to changes in mesangial function and the progression of glomerular sclerosis. Therefore, in the next experiment, the proteoglycans (PGs), one of the components of extracellular matrix, were analyzed by the column chromatography to clarify qualitative changes in the PGs such as the molecular size and charge density. Results obtained from this experiment indicate that the sclerotic glomeruli synthesize the PGs with different molecular size and charge density from normal glomeruli. It is concluded from these experiments that the abnormality of the mesangial function and the synthesis of PGs, the components of the extracellular matrix, may lead to the progression of FGS. Namely, the qualitatively altered PGs may cause abnormal interactions with other components of matrix, which lead to changes in mesangial function, death of mesangial cell and the progression of FGS.

Animals↗

[Localization of spinal tumors by MRI].

Exact localization of the spinal tumors is particularly important for differential diagnosis and surgery. Therefore, it was attempted to evaluate the diagnostic accuracy of MRI in localizing the spinal tumors exactly. Nineteen cases of spinal cord tumors, being localized in the intradural extramedullary, extradural and both intradural and extradural spaces, were studied with MRI. Intradural extramedullary tumors showed small CSF spaces just below and above the tumor which were demonstrated as CSF intensity on T1 and T2 weighted images. Although extradural tumors did not show CSF spaces, there was extradural sign or dural density between the tumor and the spinal cord. Intradural and extradural tumors were outlined as having both characteristics. Signal intensities of the spinal tumors were not characteristic for specific histology. Gd-DTPA was quite useful for accurate localization of the tumors. In comparison with myelography, MRI was superior to myelography in extradural tumors and equally useful for intradural and extradural tumors, but it was less diagnostic in intradural extramedullary tumors. In general, MRI was quite useful in localizing the spinal tumors exactly and the accuracy of MRI was quite high. In the near future this technique will replace myelography and other radiologic methods.

Adult↗

Studies on the nephrotoxicity of aminoglycoside antibiotics and protection from these effects. (5). Interaction of tobramycin with latamoxef in vitro.

Interaction of tobramycin (TOB) with latamoxef (LMOX) was studied in vitro. Solutions containing TOB alone, LMOX alone or both of these compounds in varying molar ratios (TOB:LMOX = 1:1, 1:2, 1:4 and 2:1) were incubated at 37 degrees C for 0.5, 1, 3 and 5 h after adjusting to pH 7.4. Aliquots sampled at a suitable time were subjected to paper electrophoresis (PE) and thin layer chromatography (TLC). In PE, the spots of TOB and LMOX were observed as single spots on the cathode and anode sides, respectively. However, the spot associated with TOB overlapped with that associated with LMOX on the cathode side when aliquots of the solution containing both TOB and LMOX were analyzed. It seemed that the degree of overlapping became stronger with an increase in incubation time, and there were no spots corresponding to TOB alone in the mixture of TOB-LMOX (1:4). TLC analysis showed that the spot of LMOX radiated fluorescence with Rf value 0.38. On the other hand, in the mixtures, there was a definite decrease in fluorescence of LMOX at the position of Rf value 0.38, compared with that of LMOX alone. Furthermore, the spot associated with LMOX, which overlapped with that associated with TOB, also appeared at the origin on the TLC plate. The ultraviolet spectrum of the mixture of TOB-LMOX (1:2) showed a decrease in the intensity of absorption of LMOX at 268 nm. These interactions between TOB and LMOX were also observed in rat serum and its filtrate in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Diagnosis of cancer with magnetic resonance imaging (MRI)].

Following a brief review of the history of magnetic resonance imaging (MRI), advantages and disadvantages of MRI are discussed in the diagnosis of malignant tumors of the various parts of the body. The advantages include high contrast resolution, no artifacts from the bones, and arbitrary imaging planes obtainable in multiple slices, whereas disadvantages include no signals from calcifications and prolonged imaging time. The roles of MRI were discussed in relation to detection of early cancers, extent of the lesions, histologic diagnosis and monitoring of treatments. Early diagnosis of tumors is successful in the central nervous system, whereas it is not accomplished in other parts of the body. Extent of the tumors or staging of the tumors can be accomplished to excellent advantage, but signal intensity is often not useful for differential diagnosis.

Bone Neoplasms↗

The clinical evaluation of the late potentials in patients with ventricular arrhythmias.

We investigated the recognition of late potentials in patients with and without organic heart diseases and spontaneous ventricular arrhythmias. None of the normal subjects had late potentials and patients with ventricular arrhythmias but no organic heart diseases, also had no late potentials as well as patients with idiopathic ventricular tachycardias. Late potentials in patients with idiopathic cardiomyopathy were noted more frequently in the dilated type than in the hypertrophic type, especially in those with high grades of ventricular arrhythmias. Patients with old myocardial infarctions had a higher rate of late potentials recognition in cases of sudden death or ventricular tachycardias. On the other hand, we observed lower rates in patients during early stage of acute myocardial infarction in spite of the evidence of a higher rate of ventricular electrical instability. There was no association between ejection fractions, wall motion scores and late potentials. However, a higher recognition of late potentials was found in patients with inferior or posterior myocardial infarction and ventricular aneurysm. We concluded that the late potential must be evaluated in each of the different groups of organic heart diseases in order to estimate the clinical value of ventricular arrhythmias.

Adolescent↗

Studies on the nephrotoxicity of aminoglycoside antibiotics and protection from these effects (4). Effects of tobramycin alone and in combination with latamoxef on the stability of rat kidney lysosomal membranes.

Effects of tobramycin (TOB) alone and in combination with latamoxef (LMOX) on the stability of rat kidney lysosomal membranes were investigated. Rats were injected with doses of TOB (90 mg/kg/day, s.c.) alone. LMOX (2,000 mg/kg/day, s.c.) alone or TOB (90 mg/kg/day, s.c.) and LMOX (2,000 mg/kg/day, s.c.) for 5 consecutive days. The rat kidney lysosomes were isolated on the 1st, 3rd and 5th days and incubated in a 0.25 M sucrose solution containing 1 mM EDTA (pH 7.0) at 37 degrees C for 20 min. After incubation, the activity of N-acetyl-beta-D-glucosaminidase (NAG) released from lysosomes was measured, and the percent NAG release was calculated as an index of the stability of lysosomal membranes. The percent releases of NAG from lysosomes of TOB alone-treated rats were 40 and 50% greater than those of normal rats on the 1st and 3rd days, respectively. On the other hand, treatment with TOB and LMOX suppressed the NAG release from lysosomes with TOB alone by about 80 to 100%. There were insignificant slight increases in the percent NAG release in LMOX alone-treated rats on the 3rd and 5th days. In addition, the in vitro study indicated that incubation of the lysosomal fraction from kidneys of normal rats with TOB (30 micrograms/ml) significantly increased the NAG release, compared with that of the non-treated lysosomal fraction. However, the preincubated mixture of TOB (30 micrograms/ml) and LMOX (50 micrograms/ml) in vitro significantly suppressed the release of NAG from lysosomes by 85%. These results suggest that the suppression of the releases of NAG from lysosomes by the combination of TOB with LMOX may contribute to the protective effect of LMOX against TOB nephrotoxicity.

Acetylglucosaminidase↗

Studies on the nephrotoxicity of aminoglycoside antibiotics and protection from these effects (3). Protective effect of latamoxef against tobramycin nephrotoxicity and its protective mechanism.

Effect of latamoxef (LMOX) against tobramycin (TOB)-induced nephrotoxicity was studied in rats. Treatment with TOB (90 mg/kg/day, s.c.) alone resulted in marked increases in the activities of urinary enzymes such as lactate dehydrogenase, N-acetyl-beta-D-glucosaminidase and lysozyme, urinary protein content and blood urea nitrogen, which peaked on the 7th or 10th day. The combination with LMOX (500, 1000 or 2000 mg/kg/day, s.c.) significantly suppressed increases in the parameters with TOB alone. The extent of this suppression roughly depended on the LMOX dosage. Although TOB alone caused pronounced histological changes such as extensive cortical proximal tubular cell necrosis, residual tubular basement membrane and cast formations in the renal cortex and medulla on the 7th day, these changes were apparently suppressed by combination with LMOX. In addition, intrarenal TOB concentrations in the rat given TOB alone were about 350, 500 and 1000 micrograms/g tissue wet weight at 3 hr, on day 3 and on day 5, respectively. On the other hand, there was a significant reduction (30-60%) in intrarenal TOB concentration by combination with LMOX. These results indicate that combination with LMOX obviously protects the rat kidney from TOB nephrotoxicity, and the protective effect may be partially due to suppression of intrarenal accumulation of TOB by LMOX.

Acetylglucosaminidase↗