Search PubMed⌕ Search

Biomedical subjects

S Kondo

Publications and source records attributed to S Kondo.

At least 577 records · Page 32Linked to original sources

Structure-activity relationship of pamamycins: effects of alkyl substituents.

Nine new pamamycin homologues were isolated from the culture broth of Streptomyces alboniger IFO 12738 using a combination of ODS and NH2 HPLCs, and their structures determined by GC-MS. The structural differences in these homologues are in the numbers and positions of methyl and ethyl groups. The aerial mycelium-inducing and growth-inhibitory activities in S. alboniger of these homologues and their antibiotic activity against Bacillus subtilis were examined. The effects of the alkyl substituents on these activities are discussed.

Antifungal Agents↗

Isolation from Streptomyces of a novel naphthoquinone compound, naphthablin, that inhibits Abl oncogene functions.

In the course of our screening for inhibitors of abl oncogene function, a culture filtrate of Streptomyces aculeolatus, induced normal flat morphology in v-abl-expressing NIH3T3 cells. The active substance was isolated through ethyl acetate extraction, silica gel column chromatography, and reverse-phase HPLC. Mass and NMR spectroscopy including HMBC revealed that it had a novel naphthoquinone structure with a monoterpene, and we named it "naphthablin". Naphthablin inhibited Abl-induced morphological transformation in v-ablts-NIH3T3 cells at around 30 micrograms/ml, and specifically inhibited RNA synthesis.

Cells, Cultured↗

[The effects of fitness-type exercise on iron status and hematological status for female college students].

Forty-two female college students underwent fitness-type exercise over a 13 week period. The students exercised an average of two times a week for 30 minute periods at 50% levels of VO2 . max. Iron status and hematological laboratory data were monitored at three points in time; at the initiation of exercise, at the termination of exercise and 3 months later. Serum ferritin levels in a third of the students were lower than 12ng/ml. Red blood cell counts decreased during exercise, and returned to the pre-exercise levels 3 months later. The number of circulatory reticulocytes and mean corpuscular hemoglobin concentration were increased significantly after the exercise and the effects were still observed 3 months later, independent of the iron status. In the lower ferritin group, erythropoietin levels decreased significantly during the post-exercise period. The average serum ferritin levels while showing no significant changes during exercise, increased significantly during the post-exercise period, in the normal ferritin group. We discussed possible mechanisms, among them iron metabolism, by which physical training may facilitate erythropoiesis. However, no definite conclusions have been reached.

Adult↗

Pharmacokinetics of human activated protein C. 1st communication: plasma concentration and excretion of a lyophilized purified human activated protein C after intravenous administration in the mouse and the rabbit.

Pharmacokinetic studies of human activated protein C (CAS 42617-41-4, APC) were investigated in mice and rabbits with 125I-labeled compound. Plasma levels of APC were determined by three different assays: total radioactivity, APC antigenicity determined by sandwich enzyme-linked immunosorbent assay (ELISA), and the amidolytic activity which was performed by immunologically captured APC. APC concentration obtained from these assays were shown to be correlated well at early times post-dose. After intravenous administration, total radioactivity in the plasma declined tri-exponentially, but antigenicity and amidolytic activity in the plasma declined biexponentially. Plasma AUC increased proportionally with the dose, and the total body clearance and t1/2 did not change significantly. In addition, no significant difference was observed between the pharmacokinetics in male and female mice. In rabbit study, the profiles of times vs APC concentration in the plasma was similar to those in mice after single bolus injection. The plasma concentrations of APC during and after infusion in rabbits were also determined. APC concentration increased during infusion and reached almost steady state at the end of infusion. The profiles of the APC concentration in benzamidine citrate plasma corresponded to the simulated curves which were characterized by the parameters obtained from the single bolus experiment. Plasma disposition profiles of the protein were studied with high performance gel chromatography method. The radioactivity in the unchanged APC was observed at 15 min after administration. At 1 h, most of the radioactivity was observed in larger molecule fraction than the intact APC. These results corresponded to the decrease of amidolytic activity in the plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pharmacokinetics of human activated protein C. 2nd communication: tissue distribution study of a lyophilized purified human activated protein C after single or repeated intravenous administration in male mice and placental transfer and milk passage study after intravenous administration in pregnant and lactating mice.

Tissue distribution studies of human activated protein C (CAS 42617-41-4, APC) were performed in mice after single or repeated administration, and placental transfer and milk passage study were investigated. At 15 min after a single intravenous administration of 125I-APC, radioactivity was mainly distributed to the blood and blood rich organ, such as liver, and then rapidly eliminated. The radioactivity distributed to tissues was almost negligible at 24 h after administration except for the thyroid. The qualitative study of the distribution of radioactivity to tissues by whole body autoradiography demonstrated the correspondence to the result of the quantitative assay of distribution of radioactivity after single administration of 125I-APC. The influence of repeated administration of APC on its pharmacokinetic disposition was studied by administering 125I-APC once a day to mice for 14 days. Though plasma radioactivity at 15 min in mice during repeated administration of 125I-APC was almost similar to that at 15 min after a single administration, the radioactivity at 24 h after administration was 2 times higher than that after a single administration. The profile of plasma radioactivity during and after repeated administration corresponded to the simulation curve which was described with the pharmacokinetic parameters obtained previously after the single administration. Distribution profile after repeated administration at 15 min after the 4th, 7th, 10th and 14th administration was almost similar to that at 15 min after a single administration except for the thyroid and spleen. In the thyroid, the radioactivity was 500 times higher than that after a single administration, and HPLC analysis demonstrated that the radioactivity was attributed to thyroglobulin. As to the spleen, the radioactivity was about 52% of that after a single administration. During the repeated administration, the spleen became larger than that after a single administration and the final weight was 2 times heavier than that of the non-treated animal. The decrease in radioactivity of the spleen during repeated administration was attributed to the hypertrophy of the organ. Placental transfer of 125I-APC was studied with pregnant mice quantitatively and qualitatively. Radioactivity distributed in fetuses was low at every point examined, and the result corresponded to the autoradiography. During lactation, radioactivity transferred to milk and milk to plasma ratio reached 5.7 after intravenous administration of 125I-APC. HPLC analysis of the milk radioactivity demonstrated that most of the radioactivity was present in the macromolecules produced by the lactating mother.

Animals↗

Natural history of renal lesions in spontaneously hypercholesterolemic (SHC) male rats.

Spontaneously hypercholesterolemic (SHC) rats become hypercholesterolemic on normal diets. SHC rats, especially males, exhibit renal lesions similar to those found in focal segmental hyalinosis/sclerosis (FGS). We presented here a detailed natural history of serum lipid, renal function and pathological changes in male SHC rats from 5 to 40 weeks of age. Increased urinary protein excretion and glomerular injury were apparent before the detection of lipid or immune deposits, indicating that the renal lesions were not caused by these deposits. Serum total cholesterol levels, already high at 5 weeks, abruptly increased in concurrence with increased urinary protein excretion, suggesting that the severe hyperlipidemia of this strain is modified by a nephrotic syndrome. By 30 weeks of age, glomerular sclerosis was evident in more than half of the glomeruli and tubular dilatation was prominent, with an abrupt increase of BUN, SCr, and urinary volume; these findings indicate a rapid progression to renal failure. Our results suggest that SHC rats would be a very useful model to investigate the process leading to glomerular sclerotic lesion and renal failure, as well as the effect of hyperlipidemia on glomerular injury.

Animals↗

Coenzyme A-dependent modification of fatty acyl chains of rat liver membrane phospholipids: possible involvement of ATP-independent acyl-CoA synthesis.

Certain species of fatty acyl chains of microsomal lipids from rat hepatocytes underwent desaturation when the microsomal fraction was incubated with CoA and NADH. For instance, 18:0, 18:2(n-6), and 20:3(n-6) incorporated into membrane lipids were gradually converted to 18:1(n-9), 18:3(n-6), and 20:4(n-6), respectively. Further, 20:5(n-3) and 18:3(n-6) were metabolized to 22:5(n-3) and 20:4(n-6) respectively, through chain elongation or chain elongation plus subsequent desaturation when malonyl-CoA was present. In contrast to esterified fatty acids, negligible change was observed for fre fatty acids under the same experimental conditions. It is apparent that ATP-independent acyl-CoA synthesis is implicated in such enzymatic modification of fatty acyl chains. The presence of either gel-filtered cytosol or bovine serum albumin markedly potentiated the reaction. However, the addition of ATP and Mg2+ did not accelerate the overall reaction induced in the presence of CoA alone. These results suggest that the pathway of CoA-dependent/ATP-independent modification of fatty acyl chains is sufficiently active to account for the desaturation and chain elongation of fatty acids esterified in membrane lipids, especially phospholipids, of living cells.

Acyl Coenzyme A↗

Changes in hepatic lobe volume in biliary tract cancer patients after right portal vein embolization.

Changes in lobar volume of the liver and in total hepatic function were studied in 19 patients with biliary tract cancer who underwent right portal vein embolization as preoperative management for extensive liver resection. Computed tomography (CT) was performed to estimate liver volume before and approximately 11 days after embolization. An indocyanine green (ICG) test was performed before and 11 to 13 days after embolization. The calculated volume of the right lobe decreased from 761 +/- 181 cm3 to 625 +/- 110 cm3 11 days after embolization (P < .0001), whereas the volume of the left lobe increased from 420 +/- 94 cm3 to 555 +/- 110 cm3 (P < .0001). Thus, portal embolization produced a gain in left lobe volume of 136 +/- 62 cm3 and an almost equivalent loss in right lobe volume. The hypertrophy ratio of the left lobe, expressed as percentage of postembolization volume of the left lobe to preembolization size, of the 5 patients with diabetes mellitus (DM) was lower than that of the 14 patients without diabetes (116.7 +/- 6.3% vs. 140.4 +/- 18.4%; P < .005). The ICG disappearance rate in 16 patients improved from 0.163 +/- 0.034 to 0.177 +/- 0.027 (P < .05). The improvement was especially evident in 9 of 14 post-jaundice patients, although the rate decreased slightly in 2 patients without jaundice. We conclude that right portal vein embolization can produce a compensatory hypertrophy of the left lobe within 11 days without seriously affecting hepatic function. In diabetic patients, however, a longer interval between embolization and operation may be needed to achieve sufficient hypertrophy of the left lobe.

Adult↗

[Cervical flexion myelopathy: clinical, morphological and biochemical studies on the soft tissues of the cervical spine in young-age operated cases].

To investigate the pathology of cervical flexion myelopathy among younger people, clinical, morphological and biochemical studies were performed in six cases (four males and two females) treated by posterior fusion. X-ray films showed, in all cases, scoliosis in the cervical spine as well as a reduction in the sagittal diameter and an anterior deviation in the spinal cord at the time of flexion. Spinal atrophy in the sagittal plane and crescent-shaped high contrast areas posterior to the dural tube were also observed on MRI images. Surgical findings, showed substantial expansion by the veins posterior to the dural tube in five cases with four showing accompanying organization. Morphological studies showed that in the musculus splenius capitis, the type 1 fibers were slightly more than in normal tissues. Moreover in one case, we observed neurogenic lesions such as the predominance and atrophy of type 2 fibers. Biochemical analyses of the collagen from muscles and skin showed immature collagen fibers, which was marked particularly in skin. The above results suggested that abnormalities in the collagen fibers in the soft tissues were related to the pathogenesis of cervical flexion myelopathy.

Adolescent↗

[A diabetic patient with bilateral carotid stenosis who developed neovascular glaucoma following cataract surgery].

A 67-year-old diabetic man suffered from right neovascular glaucoma following the ipsilateral cataract surgery. Three years later, he underwent left cataract surgery and again developed left neovascular glaucoma after the operation. Fluorescein angiogram showed a marked delay in retinal circulation. Moreover, severe stenosis of bilateral carotid origins and reflux of bilateral ophthalmic arteries were ascertained by neurosonographical examination such as duplex cervical echography and transcranial Doppler, as well as an angiogram. Brain imaging demonstrated asymptomatic watershed infarction in the left parieto-occipital cortex. Chronic ocular ischemia caused by carotid stenosis is one of the decisive risk factors for secondary glaucoma after cataract surgery. Preoperative neurosonographical screening tests are required to decrease ocular surgery complications, especially in the aged, and diabetic patients.

Aged↗

Binding affinity of N3-substituted uridine for synaptic membrane and their CNS depressant effects.

The binding affinity for synaptic membrane from bovine thalamus of N3-phenacyl substituted pyrimidine nucleosides having CNS depressant activity was examined by radio receptor assay. N3-Phenacyl derivatives of uridine, thymidine, deoxyuridine, 6-azauridine and arabinofuranosyluracil inhibited specific [3H]uridine binding and exhibited hypnotic activity. However, N3-phenacyl-2',3'-O-isopropylideneuridine, of which structure was different from sugar moiety of N3-phenacyluridine, showed neither the binding affinity nor the hypnotic activity. The results indicated that CNS depressant effect of pyrimidine nucleoside derivatives might relate to uridine binding affinity, so called uridine receptor.

Animals↗

Vascular endothelial growth factor and platelet-derived endothelial cell growth factor are frequently coexpressed in highly vascularized human breast cancer.

Vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) are known to be angiogenic growth factors in vitro and in vivo. In this study, we have investigated the relationship between VEGF expression and PD-ECGF expression in human breast cancer tissues using immunocytochemical methods. Of 152 primary breast cancers, 84 (55.3%) and 71 (46.7%) were positive for VEGF and PD-ECGF, respectively. Fifty-three (63. 1%) of 84 VEGF-positive tumors had a PD-ECGF-positive phenotype, whereas only 18 (26.5%) of 68 VEGF-negative tumors had a PD-ECGF-positive phenotype. There was a significant correlation between the VEGF expression and PD-ECGF expression (P < 0.01). As a single factor, VEGF expression and PD-ECGF expression were significantly associated with an increase in the microvessel density assessed by the immunocytochemical analysis using antifactor VIII-related antigen mAb. Interestingly, in addition, of 53 tumors with more than 100 microvessel counts/1 mm2, 40 (75.5%) had both VEGF- and PD-ECGF-positive phenotypes. It was found that VEGF and PD-ECGF were frequently coexpressed in highly vascularized tumors with high microvessel counts. It is suggested that VEGF and PD-ECGF might cooperatively function in the neovascularization of human breast cancer.

Breast Neoplasms↗

Fluid shear stress increases the expression of thrombomodulin by cultured human endothelial cells.

Endothelial cells (ECs) cultured from human umbilical vein were exposed to medium flow in a flow-loading chamber, and changes in thrombomodulin (TM) expression were examined by flow cytometry and enzyme linked immunosorbent assay with monoclonal antibody. The expression of TM antigen was increased time- and shear stress-dependently by flow, and when exposed to a shear stress of 15 dynes/cm2 for 24 hr, it increased to approximately 200% of the stationary control level. Reverse transcriptase-polymerase chain reaction showed that TM mRNA levels in ECs also increased in response to flow. TM mRNA began to increase one hour after the application of shear stress of 15 dynes/cm2 and reached a maximum (approximately 330% of stationary control) after eight hours. These results, demonstrating an up-regulating effect of flow on TM expression in ECs, suggest that shear stress may be an important modulator of intravascular blood coagulation.

Antibodies, Monoclonal↗

[High-speed/high resolution teleradiology system based on university microwave network].

A high-speed, high-resolution teleradiology system with full duplexing based on the Shinshu University Video and Communication Network System (SUNS) using Giga-Herz microwaves is described. The LAN at Nagano Red-Cross Hospital and The Radiology Department of Shinshu University Hospital are interfaced to a personal computer with a laser film digitizer, interactive display, and network interface. The throughput per digitized high-resolution radiographic image was 65 sec, and the mean transmission rate was 805 kilobit per sec. Teleradiology conferencing is also possible with this system. Radiologists at both hospitals interactively observe the same high-resolution images on the CRT screen using mouse cursor synchronization.

Computer Communication Networks↗

Acidification is essential for maintaining the structure and function of lytic granules of CTL. Effect of concanamycin A, an inhibitor of vacuolar type H(+)-ATPase, on CTL-mediated cytotoxicity.

An inhibitor of vacuolar type H(+)-ATPase, concanamycin A (CMA), inhibited the specific cytolytic activity of a CD8+ CTL clone, OE4. The inhibitory effect was observed when the effector cells, and not the target cells, were pretreated with CMA. CMA did not seem to inhibit early events, inasmuch as effector/target conjugate formation remained unaffected. Although CMA treatment of OE4 resulted in a slight decrease in the efficiency of granule exocytosis in response to anti-CD3 stimulation, the most prominent effect was a marked reduction of perforin activity and DNA degradation activity in lytic granules. Western blotting analysis indicated a drastic decrease in the amount of perforin in CMA-treated cells. Fluorescent microscopic observation of OE4 stained with acridine orange indicated that CMA raised the pH of the lytic granules. Under transmission electron microscopy, striking morphologic changes in cytoplasmic granular structures were observed after CMA treatment of OE4. The lytic granules of OE4 had homogeneously stained large cores and numerous small vesicles that filled peripheral areas. In contrast, the lytic granules of CMA-treated OE4 showed irregular shapes with no small vesicles, but with cores that became rough and loose. Vacuoles with no structure in them were seen occasionally. These results suggest that acidification through vacuolar type H(+)-ATPase is essential to maintain the structure and function of lytic granules.

Acid-Base Equilibrium↗

[Micro-wave local area network for radiological image transmission].

Shinshu University consists of five campuses in different locations, a situation that presents some problems in communication. To solve this problem, the Shinshu University Video and Data Network System (SUNS), which includes a high-speed audio-visual transfer function, has been developed and utilized for pre- and postgraduate education, administrative teleconferences, and local telephone (PBX) and Fax services. In 1988, a cooperative group for the study of radiographic image processing was organized, consisting of staff members of Shinshu University Hospital in Matsumoto, the Faculty of Engineering in Nagano (75 km from Matsumoto) and the Faculty of Textile Science and Technology in Ueda (45 km from Matsumoto). The system has been developed with a pair of personal computer (PC)-based interactive image workstations and high-speed digital telecommunication interfaces to the SUNS. A transmission time of 878 kbps has been attained, including the time needed for read/write onto the PC hard disk. Image data thus transferred from the hospital have been utilized for the study of image processing by researchers in the Faculty of Engineering, and the processed images have been sent back to the hospital for evaluation of clinical efficacy of the processing by diagnostic radiologists. This kind of microwave network is a promising alternative for high-speed data transmission for radiological images and their processing.

Computer Communication Networks↗