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Biomedical subjects

J Kato

Publications and source records attributed to J Kato.

At least 181 records · Page 10Linked to original sources

Abrogation of autoimmune disease in Lyn-deficient mice by the mutation of the Btk gene.

Lyn and Btk play a critical role in B cell development and intracellular signaling. Lyn-deficient mice exhibit splenomegaly, elevated serum levels of IgM, production of autoantibody and glomerulonephritis with age. On the other hand, xid mice, which carry a point mutation in the btk gene, show a decrease in numbers of peripheral mature B cells, reduced serum levels of IgM and IgG3, disappearance of CD5+ B-1 cells, and low proliferative response to anti-IgM or LPS stimulation in vitro. In order to investigate the interaction between Lyn and Btk during B cell development, we established lyn-deficient xid mice. Lyn-deficient xid mice exhibited greatly reduced numbers of peripheral mature B cells, disappearance of CD5+ B-1 cells, markedly reduced serum levels of IgM and IgG3, low proliferative response to anti-IgM or lipopolysaccharide stimulation and no evidence for autoimmune disease. In addition, splenomegaly in lyn-deficient mice, which was mainly due to the accumulation of Mac-1+, cytoplasmic IgM+ lymphoblast-like cells, was also diminished in lyn-deficient xid mice. Thus, immunological abnormalities found in lyn-deficient mice were strongly affected by the absence of Btk. The present results suggest that the autoimmune symptoms in lyn-deficient mice may be caused by not only the abnormal response of B-2 cells but also that of B-1 cells, and that the interaction between Lyn and Btk is partly in tandem at the signaling pathway in B cells.

Agammaglobulinaemia Tyrosine Kinase↗

Home blood pressure measurement has a stronger predictive power for mortality than does screening blood pressure measurement: a population-based observation in Ohasama, Japan.

OBJECTIVE: To compare the predictive powers of self-measurement of blood pressure at home (home blood pressure measurement) and casual (screening) blood pressure measurement for mortality. DESIGN: A prospective cohort study. SUBJECTS AND METHODS: We obtained home and screening blood pressure measurements for 1789 subjects aged > or = 40 years who were followed up for a mean of 6.6 years. The prognostic significance of blood pressure for mortality was determined by the Cox proportional hazards regression model adjusted for age, sex, smoking status, past history of cardiovascular disease, and the use of antihypertensive medication. RESULTS: When the home blood pressure values and the screening blood pressure values were simultaneously incorporated into the Cox model as continuous variables, only the average of multiple (taken more than three times) home systolic blood pressure values was significantly and strongly related to the cardiovascular mortality risk. The average of the two initial home blood pressure values was also better related to the mortality risk than were the screening blood pressure values. CONCLUSIONS: Home blood pressure measurement had a stronger predictive power for mortality than did screening blood pressure measurement for a general population. This appears to be the first study in which the prognostic significances of home and screening blood pressure measurements have been compared.

Adult↗

[Evaluation of a new method for susceptibility testing against fastidious and unusual bacteria].

The susceptibilities of 154 clinical isolates of fastidious and unusual bacteria were determined by the Etest, and were compared with the MICs for these strains obtained by the agar dilution method. Antimicrobial agents; benzylpenicillin, ampicillin, cefotaxime, imipenem, erythromycin, clindamycin and minocycline were used in this study. In general, the Etest MICs were rapidly and easily interpreted. The Etest MICs agreed within +/- 1 log2 and +/- 2 log2 dilution, 87.6% and 98.2% respectively in all strains tested. MICs of vancomycin with the Etest for S. pneumoniae and other Streptococci tended to be 1 to 2 log2 dilution higher than those of the agar dilution method. MICs of erythromycin for the other Streptococci also tended to be 1 to 2 log2 dilution higher. However, there were no significant differences for H. influenzae, Campylobacter spp., H. pylori, Capnocytophaga spp., E. corrodens, M. catarrhalis, N. gonorrhoeae, Corynebacterium spp., L. monocytogenes and Anaerobic bacteria. As mentioned above, the Etest represent a potential method for antimicrobial susceptibility testing of these fastidious and unusual bacteria.

Bacteria↗

[Immunoglobulin production by human peripheral B cells against Staphylococcus aureus].

Immunoglobulin (Ig) production by human B cells in thymus-independent (TI) and -dependent (TD) immune response against Staphylococcus aureus was investigated in vitro. Highly purified human peripheral B cells were cultured either in the presence of formalinized Cowan I strain Staphylococcus aureus (SAC) or with anti-CD3 stimulated T cells, and Ig content in supernatants was analyzed after 10 days of culture by specific sandwich ELISA. When activated with SAC in the absence of T cells, B cells produced minimal amounts of Ig. In the presence of interleukin-2 (IL-2) or supplemental recombinant CD40 ligand plus IL-2, Ig production by SAC-induced B cells was dramatically enhanced. When cultured with T cells stimulated with low concentrations of anti-CD3 or when cultured with smaller numbers of T cells, B cells produced large amounts of Ig, whereas T cells stimulated with higher concentrations of anti-CD3 or large numbers of T cells failed to induce effective Ig secretion by B cells. These findings suggest that TI immune response against Staphylococcus aureus is strongly enhanced in the presence of activated T cells in an antigen non-specific manner, indicating its critical role in the local humoral immune defense. Moreover, it is indicated that the secretion of Ig induced by TD antigens participates in the immune defense against Staphyloccocus aureus dependent on activated T cell/B cell ratio or an impact of CD3 stimulation on T cells.

Antibodies, Bacterial↗

Enhanced utilization of phosphonate and phosphite by Klebsiella aerogenes.

Klebsiella aerogenes ATCC 9621 was able to utilize phosphonates (Pn), including aminoethylphosphonate, ethylphosphonate, methylphosphonate (MPn), and phosphonoacetate, and inorganic phosphite (Pt) as sole sources of phosphorus (P). The products of the phn gene cluster were absolutely required for Pn breakdown and Pt oxidation to inorganic phosphate (Pi) in this organism. To determine if K. aerogenes ATCC 9621 could be engineered to enhance the utilization of Pn and Pt, a multicopy plasmid, pBI05, which carried the entire phn gene cluster, was introduced into this strain. Despite the increased dosage of the phn genes, K. aerogenes ATCC 9621(pBI05) could utilize only up to 1.1-fold more Pn and Pt than did the control strain with the parent vector alone. These results suggested that Pi, which was generated from Pn and Pt, might limit further utilization of these P compounds. Consequently, to convert the resulting Pi to polyphosphate (polyP), the plasmid pKP28, which carried the K. aerogenes ppk gene (which encodes polyP kinase), was introduced into K. aerogenes ATCC 9621(pBI05). Overexpression of the ppk gene in K. aerogenes ATCC 9621(pBI05, pKP28) resulted in a 2.5-fold increase in Pt utilization over that of the control strain. This recombinant strain also accumulated approximately sixfold more P than did the control strain when the cells were grown with MPn as a sole source of P.

Biotransformation↗

Development of a genetic transformation system for an alga-lysing bacterium.

Four marine bacteria, Alteromonas sp. strains A27, A28, A29, and A30, that lyse the diatom Skeletonema costatum NIES-324 were isolated from coastal seawater samples. They were also able to lyse the diatoms Thalassiosira sp. and Eucampia zodiacs and the raphidophycean flagellate Chattonella antiqua. Cryptic indigenous plasmids, designated pAS28 and pAS29, were detected in Alteromonas sp. strains A28 and A29, respectively. These plasmids appeared to be similar based on size and restriction site analysis. A shuttle vector that replicates in Escherichia coli and Alteromonas sp. strain A28 was constructed by fusing pAS28 and E. coli vector pCRIIc. The 16-kbp chimeric plasmid, designated pASS1, had the ability to transform strain A28 at a frequency of 10(6) transformants per microg of DNA. Deletion analysis of pASS1 showed that the 4.7-kb EcoRI-HindIII region of pAS28 was essential for plasmid maintenance in strain A28. This EcoRI-HindIII fragment contained an open reading frame which appeared to encode a 708-amino-acid protein.

Animals↗

Immunohistochemical study of the innervation of the boundary area of the hard and soft palates of the rat.

The palatal mucosa plays an important role for patients using full dentures. The posterior ridge of the denture is designed to fit on the border between the hard and soft palates; accordingly, this boundary area is of importance when the outline of the denture is designed. In the present study, a rich supply of nerve fibers was found in the mucosa of the boundary area of the hard and soft palates of the rat. An immunocytochemical examination revealed nerve fibers containing protein gene product 9.5 (PGP 9.5), calcitonin gene-related peptide (CGRP), substance P (SP), pituitary adenylate cyclase-activating peptide, vasoactive intestinal polypeptide (VIP), C-terminal flanking peptide of neuropeptide Y (c-PON), or nitric oxide synthase (NOS). Thin nerve fibers with PGP 9.5, CGRP, or SP penetrated into the epithelium, reaching beneath the cornified layer and terminated as free nerve endings. VIP-, c-PON- and NOS-containing nerve fibers were distributed in the connective tissue. Many of the VIP- and c-PON-containing nerve fibers were associated with blood vessels. In addition, nerve fibers containing PGP 9.5, CGRP, SP and c-PON were observed around, and penetrating into, the taste buds in the boundary area.

Animals↗

Adrenomedullin: a possible autocrine or paracrine inhibitor of hypertrophy of cardiomyocytes.

Adrenomedullin (AM), a potent vasodilator peptide, exists in the cardiac ventricle; however, the role of AM in the ventricular tissue remains unknown. In the present study, we investigated the production and secretion of AM in cultured neonatal rat cardiomyocytes, and we examined the effect of AM on de novo protein synthesis in these cells by measuring [14C]phenylalanine incorporation. The cardiomyocytes cultured with serum-free media secreted AM into the media in a time-dependent manner at the rate of 12.2+/-0.5 fmol/10(5) cells/48 hours (mean+/-SEM). Angiotensin II (1 micromol/L) or 10% fetal bovine serum significantly (P<.01) increased the AM secretion by 115% and 305%, respectively. In addition, Northern blot analysis of total RNA extracted from the myocytes disclosed the expression of prepro-AM mRNA of 1.6 kb. Synthetic AM at 1 micromol/L significantly reduced the 10(-6) mol/L angiotensin II- and 10% fetal bovine serum-stimulated [14C]phenylalanine incorporation into the cells, by 16% (P<.05) and 20% (P<.01), respectively. The inhibitory effect of AM on the angiotensin II-stimulated [14C]phenylalanine incorporation was abolished dose-dependently by a calcitonin gene-related peptide receptor antagonist, CGRP(8-37). Furthermore, blockade of the action of endogenous AM by either 10(-6) mol/L CGRP(8-37) or anti-AM monoclonal antibody significantly enhanced the basal and 10(-6) mol/L angiotensin II-stimulated [14C]phenylalanine incorporation. In summary, cultured neonatal rat cardiomyocytes produce and secrete AM, and the secreted AM inhibits the protein synthesis of these cells. Thus, AM may act on cardiomyocytes as an autocrine or a paracrine factor modulating the cardiac growth.

Adrenomedullin↗

Cyclic AMP delays G2 progression and prevents efficient accumulation of cyclin B1 proteins in mouse macrophage cells.

In mouse macrophage cells, the increase of the intracellular cAMP level activates protein kinase A (PKA) and results in inhibition of cell cycle progression in both G1 and G2/M phases. G1 arrest is mediated by a cdk inhibitor, p27Kip1, which prevents G1 cyclin/cdk complexes from being activated in response to colony stimulating factor-1, whereas inhibition of G2/M progression has not been fully elucidated. In this report we analyzed the effect of cAMP on G2/M progression in a mouse macrophage cell line, BAC1.2F5A. Flow cytometric analysis and mitotic index measurement using both synchronized and asynchronized cells revealed that addition of cAMP-elevating agents (8-bromoadenosine 3':5'-cyclic monophosphate and 3-isobutyl-methyl-xanthine), although they did not affect S phase progression or M/G1 transition, temporarily arrested cells in G2 but eventually the cells proceeded to M phase, resulting in about 4 hours delay of G2 progression. Timing of cyclin B1/Cdc2 kinase activation was also retarded by about 4 hours, which was accompanied by inhibition of efficient accumulation of cyclin B1 proteins. Initial induction and accumulation of cyclin B1 mRNA were not hampered, but the half life of cyclin B1 proteins was significantly shorter during G2 phase in the presence of cAMP-elevating agents compared with that of the cells blocked from progressing through M phase by nocodazole. These results imply that the cAMP/PKA pathway regulates G2 phase progression by altering the stability of a crucial cell cycle regulator.

Animals↗

Evaluation of spray cycle bioreactor using L-alanine degradation by Candida maltosa.

The oxygen-supply capability of a spray cycle reactor was evaluated by using it for oxidative degradation of L-alanine. The volumetric oxygen transfer coefficient, kLa, was evaluated as a parameter for the oxygen supply. The liquid circulation rate in the spray cycle reactor was represented in terms of the number of circulations. The kLa increased with the number of circulations, especially by stirring in the reservoir vessel, reaching 272/h at 4.4/min of circulation numbers. This value was 1.4 times higher than that without stirring. The L-alanine degradation rate increased as the cell growth was promoted, and as the circulation numbers increased. Finally, the spray cycle reactor was evaluated by the specific degradation rate. This rate increased in proportion to the kLa, and was 8.8 times higher than that in the jar fermentor, suggesting that the spray cycle reactor is superior for oxygen-demanding fermentation.

Alanine↗

Discrepancy between screening blood pressure and ambulatory blood pressure: a community-based study in Ohasama.

We investigated factors underlying discrepancy between screening blood pressure and daytime ambulatory blood pressure (the difference) in a community-based population in northeastern Japan. Screening and ambulatory pressures were measured in 706 untreated subjects aged 20 yr or older. We analyzed the effects of age and blood pressure on the difference and then performed multivariate stepwise linear regression analysis using the difference as the dependent variable. The systolic difference positively correlated with age in men. Women in their 40s exhibited a large difference, disturbing the linear relationship between the difference and age. The difference positively correlated with the screening pressure in men and women. A positive difference (screening pressure > ambulatory pressure) was observed at screening pressures above 130/75 mmHg. The difference inversely correlated with the ambulatory pressure. Multivariate analysis demonstrated that body mass index and male sex were positively associated with the systolic and diastolic blood pressure differences. The daytime pulse rate was negatively associated with the systolic difference, and the standard deviation of daytime diastolic ambulatory blood pressure was positively associated with the diastolic difference. The diastolic difference in subjects with isolated systolic hypertension based on the screening pressure was significantly smaller than that in subjects with systolic/diastolic hypertension. The difference in subjects with isolated systolic hypertension based on ambulatory pressure was significantly higher than that in systolic/diastolic hypertension. When white-coal (isolated screening) hypertension was defined as a screening systolic pressure > or = 140 mmHg, a diastolic pressure > or = 90 mmHg, or both, and a 24-h ambulatory pressure < 136/87 mmHg in men and < 131/86 mmHg in women, white-coat (isolated screening) hypertension was present in 79 (56.8%) of 139 subjects with screening hypertension. The results confirm that the discrepancy between screening and ambulatory blood pressure is due to a variety of factors, including age, sex, blood pressure levels, and baroreflex function. Our results indicate that screening blood pressure in elderly hypertensive patients should be evaluated carefully.

Adult↗

Dissociation of adrenomedullin concentrations in plasma and cerebrospinal fluid in pregnant and non-pregnant women.

Adrenomedullin (AM), a potent vasodilator peptide, has been shown to act within the central nervous system to modulate fluid and electrolyte balance. AM-immunoreactive cells have been found in the anterior pituitary gland and the choroid plexus of humans. In addition, AM activity has been implicated in the regulation of maternal circulation during pregnancy. To determine the relationship between AM concentration in the cerebrospinal fluid (CSF) and plasma, we measured AM levels in CSF and plasma of pregnant (group P, n = 12) and non-pregnant (group NP, n = 10) women scheduled to undergo gynecologic or obstetric surgery. In both groups, the concentration of AM in the plasma exceeded that in the CSF. Plasma AM concentration was significantly higher in pregnant than non-pregnant women (17.3+/-5.8 vs 5.1+/-1.4 pmol/l, mean +/- S.D.; P<0.01), whereas CSF AM concentration did not differ between the two groups (1.3+/-0.9 and 0.9+/-0.4 pmol/l in groups P and NP respectively). No significant correlation was found between AM concentrations in the CSF and plasma. The present findings suggest that AM is present in the CSF and that its concentration in the CSF is regulated independently from that in the plasma.

Adrenomedullin↗

[Effect of bisoprolol, a beta 1-selective beta-blocker, on lipid and glucose metabolism and quality of life in elderly patients with essential hypertension].

The present study investigated the effect of bisoprolol, a beta 1-selective beta-blocker without intrinsic sympathomimetic activity (ISA), on lipid and glucose metabolism and quality of life (QOL) in elderly patients with essential hypertention. Bisoprolol at doses of 5-10 mg was administered once daily for 12 weeks to 60 non-elderly and 21 elderly outpatients with mild to moderate essential hypertension. In both groups bisoprolol significantly decreased both systolic and diastolic blood pressures and significantly reduced pulse rates to the same extent. The levels of serum cholesterol, HDL-cholesterol and triglyceride, and the response of plasma glucose and insulin to 75 g oral glucose load, were not changed in either group by the bisoprolol treatment. Bisoprolol significantly improved QOL in both groups. Bradycardia, a side effect attributable to bisoprolol, was noted in only one patient in the elderly group. These results suggest that bisoprolol is a safe and useful antihypertensive drug in elderly and non-elderly patients with essential hypertension.

Adrenergic beta-Antagonists↗

[Surgery and multidisciplinary treatment for colorectal cancer].

Evaluation of surgery and multidisciplinary treatment for colorectal cancer was performed based on the review of the results of clinical trials. Although most improvement in prognosis for colorectal cancer patients was obtained by the development of surgical techniques until the mid-70's, further extended surgery could not have demonstrated the obvious improvement in survival after the 80's. In this regard, various multidisciplinary treatments were evaluated by a meta-analysis of clinical trials. Among those modalities, preoperative irradiation for rectal cancer, postoperative adjuvant chemotherapy for resected colorectal cancer and biochemical modulation of 5-fluorouracil by methotrexate or leucovorin for advanced colorectal cancers proved to be significantly effective for improvement of prognosis. Clinical trials of immunochemotherapy using either levamisole or PSK for resected colorectal cancers, a trial of hepatic artery infusion for liver metastasis, and a trial of an adjuvant monoclonal antibody treatment, were also reported to demonstrate significant effects. For further progress in multidisciplinary treatment for colorectal cancers, standardization of the appropriate surgical technique for each stage of the disease is much anticipated.

Antineoplastic Combined Chemotherapy Protocols↗

[Suppressive effect of isoflurane on somato-sympathetic reflexes in cats].

Effects of isoflurane on the reflex activity of the sympathetic nervous system were investigated in 35 cats by observing alteration of the amplitudes of somato-sympathetic medullary reflex potentials. A and C-reflex potentials, which are induced from lumbar sympathetic trunk by electric stimulation of ipsilateral femoral nerve are known to arise from A-fiber group and C-fiber group, respectively. One or two percent isoflurane in oxygen was administered for 30 minutes, because it is known that I MAC of isoflurane in cats is 1.61%. The amplitude and latency of the potentials were measured during and after inhalation of the test drug, and the results were presented as percentage change from that at prior levels of inhalation as control. The results were as follows. (1) The amplitudes of A- and C-reflex potentials were suppressed dose-dependently in rats with intact brain. (2) The amplitudes of both potentials increased by decerebration at midbrain level. (3) In decerebrate cats, the amplitudes of both potentials at each inhaled concentration were suppressed to the similar levels at inhalation of 2% isoflurane in intact cats, although a slight difference between intact and decerebrated cats was observed with A-potentials during inhalation of 1% isoflurane. (4) The latencies were prolonged slightly in A-reflex potentials, only in intact cats at both concentrations. (5) Blood pressure decreased during inhalation of the test drug in every condition, but their dose-dependencies were evident only in intact cats. (6) Selective suppression of C-reflex potential by inhalation of isoflurane could not be demonstrated. These results suggest that isoflurane has a strong suppressive effect on sympathetic reflex center in medulla oblongata with was demonstrated by greater degree of suppression of the reflex responses in decerebrate cats than that in intact animals. It was concluded that the effect of isoflurane on sympathetic nervous system is similar to that of halothane.

Anesthetics, Inhalation↗

[Two cases of functioning parathyroid cysts].

Two cases of functioning cysts are reported. The first patient was a 48-year-old man who underwent percutaneous cyst puncture for a palpable mass in the neck at another hospital. Hypercalcemic crisis brought the patient to Koga General Hospital. The second patient was a 69-year-old woman with the complaint of discomfort in the right neck of several years duration and with a palpable mass identified on physical examination at a local hospital. Both patients had high serum calcium and parathyroid hormone (PTH) levels and were diagnosed as having functioning parathyroid cysts by imaging studies including ultrasonography, computed tomographic scan, magnetic resonance imaging and scintigraphy. After parathyroidectomy, their serum calcium and PTH levels became normal, but calcium supplement was necessary in the first patient. To our knowledge, these are the 40th and 41st cases reported in the Japanese literature.

Aged↗