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Biomedical subjects

M Kobayashi

Publications and source records attributed to M Kobayashi.

At least 559 records · Page 31Linked to original sources

Levels of beta-human chorionic gonadotropin in cerebrospinal fluid of patients with malignant germ cell tumor can be used to detect early recurrence and monitor the response to treatment.

BACKGROUND: Tumor marker-producing germ cell tumors of the central nervous system are malignant and require radiation and/or chemotherapy. Although serum beta-human chorionic gonadotropin (hCG) has been used to monitor the course of treatment, the levels of beta-hCG in the cerebrospinal fluid (CSF) have not been measured routinely in the clinic. To determine whether they can be used to evaluate parameters of tumor status, such as progression or response to therapy, levels of beta-hCG in the serum and CSF of patients with germ cell tumors were studied. METHODS: Fifty-four paired samples of CSF and serum were taken from seven patients with germ cell tumor and their beta-hCG levels were measured. Beta-hCG was negative in both serum and CSF in 11 instances and the levels in the other 43 paired samples were analyzed for any correlation or relationship to therapy. They were also compared with the clinical courses. RESULTS: The mean CSF beta-hCG level was 11.5 mIU/ml, which was significantly higher than the level in serum (3.5, p = 0.002). In all the paired samples except for one time point, the level in CSF was higher than that in serum. Out of 43 instances where the beta-hCG level in CSF was elevated, the level in serum was elevated in only 16 (37.2%). Among cases of recurrent malignant germ cell tumor, there were nine instances of recurrence or progression despite therapy. In all five instances where beta-hCG CSF levels were measured, the levels were elevated prior to any increase or detectability of the serum values. CONCLUSION: It seems likely that the level of beta-hCG in CSF is a good marker for monitoring tumor recurrence or evaluation of treatment results.

Adolescent↗

Prevalence of Japanese dialysis patients with an A-to-G mutation at nucleotide 3243 of the mitochondrial tRNA(Leu(UUR)) gene.

BACKGROUND: A high prevalence of an A-to-G mutation at nucleotide 3243 of the mitochondrial genome in patients with diabetes mellitus (DM) and/or deafness has been reported previously. We investigated the prevalence of this mutation in Japanese dialysis patients with associated DM and/or deafness. METHODS: We studied 106 dialysis patients with DM, 26 with DM and deafness, and 26 with deafness alone, using peripheral leucocytes to detect an A-to-G transition at nucleotide 3243 of the mitochondrial gene. RESULTS: We identified this transition in 1 of 26 patients with DM and deafness. None of the 106 DM or 26 dialysis patients with deafness but no DM was positive for this mutation. A 42-year-old male patient on continuous ambulatory peritoneal dialysis (CAPD) who carried this mutation had a 20-year history of sensory hearing loss as well as hypertrophic cardiomyopathy. CONCLUSION: We found that a mitochondrial gene mutation at nucleotide 3243 was present in one dialysis patient with NIDDM and deafness. The prevalence of this mutation was found to be below 1% in diabetic end-stage renal disease patients in Japan.

Adult↗

Cytokines and T-cell responses in superantigen-related glomerulonephritis following methicillin-resistant Staphylococcus aureus infection.

BACKGROUND: We have previously reported that 10 patients who developed glomerulonephritis (GN) in association with methicillin-resistant Staphylococcus aureus (MRSA) infection showed a marked increase in DR+CD4+ and DR+CD8+ subsets of T cells and in T cells expressing several T-cell receptor (TCR) V beta+cells, perhaps representing V beta-specific T-cell activation by MRSA-derived superantigens (Kidney Int 1995; 47: 207-216). In this study we examine cytokine levels, T-lymphocyte subsets, natural killer NK cells, memory T cells, and the expression of IL-2 receptors in order to better understand the role of bacterial superantigens and cytokines in the pathogenesis of MRSA-associated GN. METHODS: Twenty-two patients with MRSA infection who later developed GN caused by staphylococcal enterotoxin were evaluated immunologically in comparison with patients whose MRSA infection was not followed by GN (non-GN group) and normal individuals. RESULTS: Among peripheral lymphocytes, the frequency of T cells expressing several TCR V betas, especially V beta 5-family TCR, was higher in the GN group than in both the non-GN group and the normal healthy control group. GN patients also showed increased serum levels of several cytokines, including tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-2, IL-6, IL-8, and IL-10, which have been implicated in the onset of nephritis. Memory cells, and IL-2 receptors also were elevated in the GN group. CONCLUSION: These results suggest that T cells activated by MRSA-derived staphylococcal enterotoxins and subsequent production of cytokines may play an important role in the pathogenesis of MRSA-associated GN.

Adult↗

Boron nutrition of cultured tobacco BY-2 cells. III. Characterization of the boron-rhamnogalacturonan II complex in cells acclimated to low levels of boron.

Cultured cells of tobacco (Nicotiana tabacum L.) BY-2 which could propagate at the same rate as the parent cells (1 mg B liter(-1)) under a lower level of boron (0.01 mg B liter(-1)) were obtained. The selected cells had swollen cell walls. In the parent cells, all the RG-II occurred as a B-RG-II complex, however, two-thirds of the RG-II occurred in a monomeric form in the selected cells.

Boron↗

Interleukin-4 inhibits interleukin-11 production by rheumatoid synovial cells.

OBJECTIVE: To examine the effect of interleukin-4 (IL-4) on IL-11 production by rheumatoid synovial cells. METHODS: Freshly isolated rheumatoid synovial cells (FRS) were obtained by collagenase digestion of rheumatoid arthritis (RA) synovial tissue specimens taken at the time of operation. Rheumatoid synovial cells at four to eight passages were used as cultured rheumatoid synovial fibroblasts (RSF). IL-11 concentration was measured by ELISA. RESULTS: IL-4 inhibited the production of IL-11 by FRS in a dose-dependent manner. This inhibition was observed in FRS obtained from six patients, and the mean inhibition was 46.5%. The inhibitory effect of IL-4 on IL-11 production was cancelled by the addition of anti-IL-4 antibody. IL-4 also inhibited IL-11 production by IL-1alpha-stimulated cultured RSF. CONCLUSION: IL-4 inhibited IL-11 production by rheumatoid synovial cells. IL-4 has a protective effect on bone resorption. On the contrary, IL-11 participates in bone resorption via osteoclastogenesis. Therefore, IL-4 may exert its protective effect on bone resorption, at least in part, via inhibition of IL-11 production in rheumatoid joints.

Arthritis, Rheumatoid↗

Trapezoid bone fracture.

Fractures of the carpal bones involve only a single bone or complex bones with or without ligament rupture. However, fractures of the trapezoid are rarely seen. Because the trapezoid is fastened to the trapezium, capitate, and scaphoid by strong ligaments, fracture or dislocation is limited by this rigid fixation. The authors present a single bone fracture of the trapezoid in a 40-year-old man. A tomogram of the carpal bone was useful in diagnosing the trapezoid fracture. The mechanism for development of fracture of the trapezoid alone is unknown. However, fracture of the trapezoid seemed to occur when the wrist joint was forced with excessive flexion stress that was placed on the trapezoid through the second metacarpal bone indirectly. This occurred in the same manner that a walnut is broken with nutcrackers.

Adult↗

Osteochondroma of the mandibular body.

We have treated four cases of osseous ostechondromas arising on the mandibular body, where this tumor rarely presents on the craniomaxillofacial bones. There were no recurrences after simple surgical resection of these tumors.

Adult↗

Recombinant human interleukin-11 decreases severity of acute necrotizing pancreatitis in mice.

Interleukin (IL)-11 has anti-inflammatory activity in animal models of gut inflammation, endotoxemia, and radiation-induced thoracic injury. The aim of the present study was to investigate the protective role of IL-11 in a model of acute necrotizing pancreatitis in mice. Acute pancreatitis was induced by administration of seven intraperitoneal injections of cerulein (50 microg/kg) at hourly intervals. Lipopolysaccharide (LPS) was injected 5 hours after the first cerulein injection. Treatment with recombinant human IL-11 (rhIL-11) was started 30 minutes before the first cerulein injection and repeated 4 hours later. Serum levels of amylase, lipase, and tumor necrosis factor (TNF)-alpha were measured at the end of the experiments. The severity of pancreatitis was evaluated by histological scoring using a semiquantitative analysis of hematoxylin and eosin-stained sections of the pancreas. Competitive reverse transcription-polymerase chain reaction (RT-PCR) was performed to quantify the intrapancreatic TNF-alpha mRNA levels. Serum amylase and lipase levels progressively increased with a maximum reached between 8 and 11 hours. Treatment with rhIL-11 significantly decreased amylase and lipase levels at 6 and 8 hours. Serum TNF-alpha peaked at 6 hours and rapidly decreased thereafter. The elevation of serum TNF-alpha was markedly inhibited by treatment with rhIL-11. Histologically, treatment of rhIL-11 reduced the severity of pancreatic injury including edema, inflammatory cell infiltration, and hemorrhage at 6 hours. Intrapancreatic TNF-alpha mRNA levels were reduced by >50% in the rhIL-11-treated group at 6 hours. In conclusion, rhIL-11 decreased the severity of experimental pancreatitis early on but not later and inhibited the intrapancreatic TNF mRNA expression in vivo, suggesting that the protective effect of IL-11 during the early stage of acute pancreatitis may be mediated, at least in part, through modulation of TNF production.

Amylases↗

A stress-inducible gene for 9-cis-epoxycarotenoid dioxygenase involved in abscisic acid biosynthesis under water stress in drought-tolerant cowpea.

Four cDNA clones named CPRD (cowpea responsive to dehydration) corresponding to genes that are responsive to dehydration were isolated using differential screening of a cDNA library prepared from 10-h dehydrated drought-tolerant cowpea (Vigna unguiculata) plants. One of the cDNA clones has a homology to 9-cis-epoxycarotenoid dioxygenase (named VuNCED1), which is supposed to be involved in abscisic acid (ABA) biosynthesis. The GST (glutathione S-transferase)-fused protein indicates a 9-cis-epoxycarotenoid dioxygenase activity, which catalyzes the cleavage of 9-cis-epoxycarotenoid. The N-terminal region of the VuNCED1 protein directed the fused sGFP (synthetic green-fluorescent protein) into the plastids of the protoplasts, indicating that the N-terminal sequence acts as a transit peptide. Both the accumulation of ABA and expression of VuNCED1 were strongly induced by drought stress in the 8-d-old cowpea plant, whereas drought stress did not trigger the expression of VuABA1 (accession no. AB030295) gene that encodes zeaxanthin epoxidase. These results indicate that the VuNCED1 cDNA encodes a 9-cis-epoxycarotenoid dioxygenase and that its product has a key role in the synthesis of ABA under drought stress.

Abscisic Acid↗

Crystallization and preliminary crystallographic analysis of the high-potential iron-sulfur protein from Thermochromatium tepidum.

The high-potential iron-sulfur protein (HiPIP) is an electron carrier between the photosynthetic reaction centre and the cytochrome bc(1) complex in the electron-transfer chain of photosynthesis. The purified HiPIP from Thermochromatium tepidum (formerly Chromatium tepidum) was crystallized in a solution of 1.4 M ammonium sulfate and 0.1 M sodium citrate pH 3.5. The crystals diffract X-rays beyond 1.4 A resolution and belong to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 47.12 (6), b = 59.59 (10), c = 23.62 (3) A. The structure was preliminarily solved by the molecular-replacement method. The crystal structure of HiPIP from T. tepidum showed that the proteins exist as monomers, although HiPIPs from several other species can form dimers.

Bacterial Proteins↗

Crystallization of retinol dehydratase from Spodoptera frugiperda: improvement of crystal quality by modification by ethylmercurythiosalicylate.

Retinol dehydratase is a sulfotransferase which is presumed to catalyze the dehydration of its substrate via a transient retinyl sulfate intermediate. Crystals (space group P2(1), unit-cell parameters a = 82.05, b = 66.61, c = 84.90 A, beta = 111.29 degrees ) are significantly improved by covalent modification of the protein with ethylmercury.

Animals↗

A case of toxic epidermal necrolysis-type drug eruption induced by oral lysozyme chloride.

We report a case of toxic epidermal necrolysis-type drug eruption. A 23-year-old man took an oral over-the-counter preparation for the common cold. A few days later, generalized erythema developed with systemic malaise and pain. A multiple blister formation followed, and Nikolsky's sign was noted on each blister. A lymphocyte stimulation test (LST) with the patient's peripheral lymphocytes strongly suggested that the eruption was attributable to lysozyme chloride which was included in the preparation taken. Following an intravenous drip of betamethasone for two weeks, the eruptions improved favorably.

Acetaminophen↗

Electron microscopic study of Langerhans cell histiocytosis.

Among the several forms of Langerhans cell histocytosis (LCH), Letterer-Siwe disease is the most acute disseminated multisystemic variant. The course of Letterer-Siwe disease is usually rapid and fatal. We report here a cases of Letterer-Siwe disease which showed a good response to chemotherapy. We also describe the unusual ultrastructural findings in the histiocyte-like cells in this case.

Antineoplastic Combined Chemotherapy Protocols↗

Characterization of the interaction of TZT-1027, a potent antitumor agent, with tubulin.

TZT-1027, a derivative of dolastatin 10 isolated from the Indian Ocean sea hare Dolabella auricularia in 1987 by Pettit et al., is a potent antimicrotubule agent. We have compared the activity of TZT-1027 with that of dolastatin 10 as well as the vinca alkaloids vinblastine (VLB), vincristine (VCR) and vindesine (VDS). TZT-1027 and dolastatin 10 inhibited microtubule polymerization concentration-dependently at 1 - 100 microM with IC50 values of 2.2 +/- 0.6 and 2.3 +/- 0.7 microM, respectively. VLB, VCR and VDS inhibited microtubule polymerization at 1 - 3 microM with IC50 values of 2.7 +/- 0.6, 1.6 +/- 0.4 and 1.6 +/- 0.2 microM, respectively, but showed a slight decrease in inhibitory effect at concentrations of 10 microM or more. TZT-1027 also inhibited monosodium glutamate-induced tubulin polymerization concentration-dependently at 0.3 - 10 microM, with an IC50 of 1.2 microM, whereas VLB was only effective at 0.3 - 3 microM, with an IC50 of 0.6 microM, and caused so-called "aggregation" of tubulin at 10 microM. Scatchard analysis of the binding data for [(3)H]VLB suggested one binding site (Kd 0.2 +/- 0.04 microM and Bmax 6.0 +/- 0.26 nM / mg protein), while that for [(3)H]TZT-1027 suggested two binding sites, one of high affinity (Kd 0.2 +/- 0.01 microM and Bmax 1.7 +/- 0.012 nM / mg protein) and the other of low affinity (Kd 10. 3 +/- 1.46 microM and Bmax 11.6 +/- 0.83 nM / mg protein). [(3)H]TZT-1027 was completely displaced by dolastatin 10 but only incompletely by VLB. [(3)H]VLB was completely displaced by dolastatin 10 and TZT-1027. Furthermore, TZT-1027 prevented [(3)H]VLB from binding to tubulin in a non-competitive manner according to Lineweaver-Burk analysis. TZT-1027 concentration-dependently inhibited both [(3)H]guanosine 5'-triphosphate (GTP) binding to and GTP hydrolysis on tubulin. VLB inhibited the hydrolysis of GTP on tubulin concentration-dependently to a lesser extent than TZT-1027, but no inhibitory effect of VLB on [(3)H]GTP binding to tubulin was evident even at 100 microM. Thus, TZT-1027 affected the binding of VLB to tubulin, but its binding site was not completely identical to that of VLB. TZT-1027 had a potent inhibitory effect on tubulin polymerization and differed from vinca alkaloids in its mode of action against tubulin polymerization.

Animals↗

TZT-1027, an antimicrotubule agent, attacks tumor vasculature and induces tumor cell death.

TZT-1027, a dolastatin 10 derivative, is an antimicrotubule agent with potent antitumor activity both in vitro and in vivo. In this study, we performed biochemical and histopathological examinations, and evaluated TZT-1027-induced tumoral vascular collapse and tumor cell death in an advanced tumor model, murine colon 26 adenocarcinoma. In addition, we studied the effects of TZT-1027 on cultured human umbilical vein endothelial cells (HUVEC). Tolerable doses of TZT-1027 induced tumor-selective hemorrhage within 1 h. This hemorrhage occurred mainly in the peripheral area of the tumor mass. Measurements of tumoral hemoglobin content and dye permeation revealed that the hemorrhage occurred firstly and tumor blood flow stopped secondarily. The vascular damage was followed by continuous induction of apoptosis of the tumor cells, tumor tissue necrosis, and tumor regression. In cultured HUVEC, TZT-1027 induced marked cell contraction with membrane blebbing in 30 min. These cell changes were completely inhibited by K252a, a broad-spectrum inhibitor of protein kinases. These effects of TZT-1027 on both tumor vasculature and HUVEC were greater than those of vincristine. In conclusion, TZT-1027 quickly attacked the well-developed vascular system of advanced tumors by a putative protein kinase-dependent mechanism, and then blocked tumor blood flow. Therefore, TZT-1027 has both a conventional antitumor activity and a unique anti-tumoral vascular activity, making it a potentially powerful tool for clinical cancer therapy.

Animals↗

Regulation of granulocyte colony-stimulating factor and parathyroid hormone-related protein production in lung carcinoma cell line OKa-C-1.

Previously we have established a clonal squamous cell carcinoma cell line OKa-C-1 derived from lung cancer of a patient with marked leukocytosis and hypercalcemia. OKa-C-1 cells simultaneously produce granulocyte colony-stimulating factor (G-CSF) and parathyroid hormone-related protein (PTHrP) at the single cell level and cause paraneoplastic syndromes in nude mice bearing the tumor. It is known that the production of G-CSF and PTHrP is individually regulated by inflammatory cytokines in various malignant cells. To investigate the common factors in the regulation of G-CSF and PTHrP production in OKa-C-1 cells, we examined the effects of some inflammatory agents [lipopolysaccharide (LPS), phorbol-12-myristate-13-acetate (PMA), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) beta and IL-6] on G-CSF and PTHrP production, by means of enzyme-linked immunosorbent assay (ELISA), immunoradiometric assay (IRMA) and quantitative reverse transcription-polymerase chain reaction (RT-PCR). TNF-alpha or IL-1beta induced both G-CSF and PTHrP production in the conditioned medium. TNF-alpha synergized with IL-1beta to significantly increase G-CSF production. In addition, TNF-alpha and IL-1beta strongly induced G-CSF mRNA with peaks at 2 and 6 h respectively. Although PTHrP production was also strongly induced by TNF-a PTHrP mRNA expression was more strongly induced by PMA than by TNF-alpha. Thus, TNF-alpha and IL-1beta could be common factors that individually and synergistically regulate G-CSF and PTHrP production in OKa-C-1 cells. Moreover, G-CSF and PTHrP production could be not only transcriptionally, but also posttranscriptionally regulated by other factors.

Animals↗

Mean corpuscular volume may be a useful index of risk for colorectal adenoma in middle-aged Japanese men.

OBJECTIVE: It has been reported that alcohol intake and folate deficiency are associated with an increased risk of colorectal adenomas and carcinomas. Mean corpuscular volume (MCV) of red blood cells has been reported to be increased in these conditions. The purpose of this study was to assess the association between MCV and risk of colorectal adenoma. METHODS: The subjects were 497 middle-aged (45-65 yr old) men who underwent both barium enema examination and total colonoscopy. The subjects answered a questionnaire regarding their alcohol consumption history, and their blood samples were analyzed. The subjects were divided into four groups three times: with or without alcoholism, and with or without adenoma according to alcohol intake, and according to the MCV value. Various variables were compared among the groups, and the odds ratios of adenoma were calculated. RESULTS: The MCV was higher in the alcoholic group than in the nonalcoholic group (p < 0.01) and in patients with adenoma than in those without adenoma (p < 0.0001). When the subjects were stratified by alcohol intake, the MCV value had a higher significant difference than alcohol intake, between patients with adenoma and those without adenoma. As for the MCV value, the odds ratio (95% confidence interval) of adenoma was 1.00 (referent); (<92), 1.20 (0.71-1.69); (> or =92 but <95), 2.61 (2.07-3.15); (> or =95 but <98); and 3.62 (2.99-4.25); (> or =98). CONCLUSION: A high MCV value may be used as a simple index of the risk of colorectal adenomas, regardless of alcohol consumption.

Adenoma↗

Mutations in interferon sensitivity-determining region of hepatitis C virus: its relation to change in viral load.

OBJECTIVE: Interferon sensitivity-determining region (ISDR) in nonstructural region 5A of hepatitis C virus (HCV) genotype-1b has been reported to be associated with viral load. Viral load is usually small in the patients with mutant type (four or more amino acid substitutions, compared with HCV-J) and large in those with wild (identical to HCV-J) or intermediate type (from one to three amino acid substitutions). A possible correlation was investigated between mutations in ISDR and alterations of viral load during the course of disease. METHODS: The sequences of ISDR were determined in eight patients with significant changes of viral load and in 11 patients without changes. RESULTS: In two of the eight patients with significant alterations of viral load, ISDR sequences changed significantly. In one patient whose viral load increased after a course of interferon therapy, the number of substitutions, compared with HCV-J, decreased from five to zero or one; the type of ISDR converted from mutant type to wild or intermediate type. In one patient whose viral load decreased significantly after two courses of interferon therapy, the number of substitutions increased from one to six; ISDR changed from intermediate type to mutant type. In the remaining six patients with changes of viral load and in the other 11 patients without changes, the sequences of ISDR did not change significantly. CONCLUSIONS: The mutations in ISDR are one of the viral factors involved in the changes in viral load during the course of disease, although the majority of other factors involved are still unknown.

Adult↗