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Biomedical subjects

M Hirata

Publications and source records attributed to M Hirata.

At least 469 records · Page 26Linked to original sources

Angioimmunoblastic lymphadenopathy. Review of 44 patients with emphasis on prognostic behavior.

In order to investigate the relationship between histologic findings and clinical behavior in angioimmunoblastic lymphadenopathy (AILD), 44 patients with AILD were reviewed. These patients comprised 24 men and 20 women with age range from 25 to 84 years of age (median, 64 years). Lymphadenopathy was observed in all patients, systemic in 37, and localized in seven. Polyclonal hypergammaglobulinemia was present in 64% of patients. Histologically clear cells or convoluted cells were observed in 36% and 48% of the patients, respectively. Univariate analysis (log-rank test) for prognostic factors revealed age, appetite, presence of clear cells, or convoluted cells were important factors. However, multivariate analysis revealed that there were no independent factors for prognosis. The presence of clear cells and/or convoluted cells were histologic signs for poor prognosis; autopsy showed that patients with the clear cells with or without convoluted cells mostly died of active disease of AILD with two cases progressing to non-Hodgkin's lymphomas and those with convoluted cells alone died of lung infection. From these findings, AILD could be divided into three groups: AILD with (1) clear cells with or without convoluted cells, (2) convoluted cells alone, or (3) neither cells. The first two groups showed poor prognosis, and the last a favorable prognosis.

Adult↗

Stimulatory effects of atrial natriuretic factor on phosphoinositide hydrolysis in cultured bovine aortic smooth muscle cells.

The effects of atrial natriuretic factor (ANF) on phosphoinositide hydrolysis were examined in preparations of cultured bovine aortic smooth muscle cells. In homogenates or particulate fractions from cultured bovine aortic smooth muscle cells, ANF and atriopeptin I increased the formation of inositol phosphates and GTPase activity. The effects on inositol phosphates were markedly enhanced with guanosine 5'[gamma-thio]triphosphate. Both atrial peptides also stimulated the formation of diacylglycerol in intact cultured cells. In these experiments, atriopeptin I was about 10-fold more potent than ANF. These studies indicate that atrial peptides have stimulatory effects on phosphoinositide hydrolysis which are mediated through a guanine nucleotide regulatory protein. The greater potency of atriopeptin I on GTPase activity and the accumulation of inositol phosphates suggests that the nonguanylate cyclase-coupled receptor for ANF (ANF-R2) mediates the stimulatory effects of ANF on phosphoinositide hydrolysis through a guanine nucleotide regulatory protein.

Animals↗

Metabolism of a thromboxane A2 antagonist in isolated rat hepatocytes.

Metabolism of a thromboxane A2 antagonist (+/-)-5-(Z)-7-(3-endo-phenylsulphonylaminobicyclo[2.2.1]hept-2- exoyl)- heptenoic acid (S-145) in isolated rat hepatocytes was examined by high-performance liquid chromatography and gas chromatography/mass spectrometry. As the hydrophobic metabolites, bis-nor S-145, tetra-nor S-145 and bis-nordihydro S-145 were identified, and two other products were estimated to be monohydroxylated S-145 and dehydrogenated S-145. On the basis of kinetics of S-145 metabolism, a metabolic pathway of S-145 in isolated hepatocytes is tentatively proposed.

Animals↗

Biological aspects and self-evaluation of shiftwork adaptation.

Two male truck drivers working in a Brazilian cellulose plant and classifying themselves as "well-" and "ill-adapted" to a shiftwork schedule of 4 days-on and 1 day-off, participated in an autorhythmometric study. Psychophysiological self-ratings (calmness, stress and alertness), oral temperature measurements and urine collections (detection of K+,Na+ and 17-OH concentrations) were performed regularly during the waking period for 15 consecutive days during the shift schedule--the midday shift (11:00 to 19:00 h), early-morning shift (03:00 to 11:00 h) and evening shift (18:00 to 02:00 h), including days-off. Cosine fitting of the data to a successive running one-day window revealed different individual temporal patterns, with the "well-adapted" subject showing a relatively stable phase relationship of the variables under study and the "ill-adapted" subject showing a less stable relationship. The different patterns could explain, at least partially, the fact that one subject feels "adapted" to shiftwork and the other not.

Adaptation, Physiological↗

A new HPLC fluorimetric method to monitor urinary delta-aminolevulinic acid (ALA-U) levels in workers exposed to lead.

A new sensitive HPLC method for the determination of urinary delta-aminolevulinic acid (ALA-U) was used to evaluate the relationship between blood-lead (Pb-B) and ALA-U levels in male workers exposed to lead. The differences between the ALA-U levels determined by this method (ALA-U-HP) and by a colorimetric method (ALA-U-CL) are discussed. The HPLC method gave values similar to the ALA-U-CL values at high ALA-U level. However, at low blood-lead levels (58 +/- 22 micrograms/l, n = 23), the mean ALA-U-HP level corrected by urinary creatinine level was one-third of the corrected ALA-U-CL level (0.83 +/- 0.14 and 2.4 +/- 0.5 mg/g creatinine, respectively). A significant increase of the mean corrected ALA-U-HP level was observed at 162 +/- 22 micrograms/l Pb-B (P less than 0.05, n = 26), while that of ALA-U-CL was observed at 245 +/- 30 micrograms/l Pb-B (P less than 0.01, n = 37). The regression equation based on the logistic model fitted well to the relationship data between the Pb-B level and the percentage of the subjects with corrected ALA-U-HP above the cut-off point (1.12 mg/g creatinine) and the expected Pb-B level for 50% response was 270 micrograms/l Pb-B, while it did not fit well to the relationship data between Pb-B level and the percentage of the subjects with corrected ALA-U-CL above the cut-off point (3.5 mg/g creatinine).(ABSTRACT TRUNCATED AT 250 WORDS)

Aminolevulinic Acid↗

Synergism between interleukin-1 beta and tumor necrosis factor-alpha in production by 3T3 cells of a chemotactic factor for rat polymorphonuclear leukocytes.

Recombinant human interleukin-1 beta (IL-1) and tumor necrosis factor-alpha (TNF) synergistically stimulated BALB/c 3T3 cells to produce a chemotactic factor for rat polymorphonuclear leukocytes (PMNs), whereas an addition of 10(-11)-10(-8) M IL-1 or TNF alone to the cell culture resulted in a slight increase in the production of chemotactic factor. The partially purified factor was not a chemokinetic but chemotactic factor for PMNs when analyzed by checkerboard analysis. The partially purified factor was trypsin sensitive and heat stable; its isoelectric point was 8.5-10, and its molecular weight was about 10 kDa as estimated by gel filtration. These results suggest that fibroblasts may participate in PMN migration to the inflammatory site where both IL-1 and TNF are released by activated inflammatory cells, including macrophages.

Animals↗

Variation of trace metals in ancient and contemporary Japanese bones.

Excavated and contemporary bones (rib cortexes) of a mature age (40-60 yr) were analyzed by atomic absorption spectrometry for the concentration of seven elements, including Ca, Cd, Cu, Fe, Mn, Ni, and Pb, with a view to historically evaluating the chemical composition of the bones. Fifty-two well-preserved specimens, obtained from western Japan, were classified into six groups according to Japanese prehistoric and historic eras (Jomon, Yayoi, Kofun, Muromachi, Edo, and Contemporary). Average concentrations of Ca were 0.20-0.33 g/g in the excavated bones and 0.17 g/g in the contemporary bones. Among the trace metals, such as Cu, Fe, Mn, and Pb, which showed remarkably elevated concentrations in the Edo era bones, Cu, Fe, and Mn were found to be strongly associated with soil contamination. Lead levels only slightly increased between the Jomon and Kofun eras, but became abruptly elevated following the Edo era. In contrast, the concentrations of Cd increased abruptly in the Yayoi era to a level with an order of magnitude higher than the Edo era, and they have recently decreased to rather low contemporary levels. This tendency becomes clearer when comparing the molar ratio of trace metals to Ca. The cause of elevated Cd concentrations in early excavated bones is discussed in relation to the mineralization of bones and the surrounding environment.

Adult↗

Stereoselective glutathione conjugation of a uricosuric diuretic.

A reduction of cellular glutathione (GSH) content was observed when isolated rat hepatocytes were incubated with a stereoisomer of a uricosuric diuretic (S-8666) at a high concentration. Subsequent studies have revealed it was due to conjugation of GSH and S-8666 (-)-enantiomer in the liver cytosol. The (+)-enantiomer strongly inhibited the conjugation reaction, therefore, GSH depletion did not take place when a racemic form of S-8666 was incubated with the liver cells. A possible chemical structure of the GSH-conjugate is tentatively proposed.

Animals↗

Glutathione conjugation of synthetic steroids in isolated rat hepatocytes.

When designing steroid drugs with multiple double bonds, the influence of glutathione conjugation on the pharmacodynamics of drug action should be considered. We have examined the effect of canrenone, a mineralocorticoid receptor antagonist, on isolated rat hepatocytes and found that 1 mM canrenone injured the hepatocytes during shortterm incubation at 37 C, while an analogue of canrenone which bears 4 double bonds (delta 1,11-CAN) did not manifest such toxicity. To further pursue this, we prepared testosterone analogues comprising multiple double bonds as model compounds, and incubated them with freshly isolated rat hepatocytes. The viability of the hepatocytes was not influenced by any of the steroids, but some of them having a double bond at the C6-C7 position reduced the cellular glutathione levels. This was found to be due to conjugation of glutathione to the C7 position of the steroid molecule, and the rate of conjugation was accelerated when an additional double bond was introduced at C1-C2 or C11-C12 positions. The finding is interesting as glucuronidation or sulfation are common as conjugation processes of steroids.

Animals↗

Ca2+ dependence of inositol 1,4,5-trisphosphate 3-kinase activity in the cytosol fraction of pig coronary artery.

1. The activity of inositol 1,4,5-trisphosphate 3-kinase in subcellular fractions of smooth muscles of the pig coronary artery was examined. 2. Incubation of [3H]inositol 1,4,5-trisphosphate (IP3) with muscle homogenates produced more polar 3H-radioactivity (probably as inositol 1,3,4,5-tetrakisphosphate, IP4) than IP3, in the Mg2+- and ATP-dependent manner, thereby indicating the presence of IP3 3-kinase activity in homogenates of the muscle. 3. Most of the kinase activity was present in the cytosol fraction. The enzyme activity was reversibly activated by Ca2+ with a half-maximal effective concentration of 2.5 x 10(-7) M. 4. The calmodulin antagonists, W-7 and chlorpromazine inhibited the Ca2+-activated enzyme activity.

Animals↗

Immunocytochemical localization of beta II subspecies of protein kinase C in rat brain.

The distribution of a subspecies of protein kinase C (PKC) encoded by the beta II sequence in rat central nervous tissue was demonstrated immunocytochemically by using antibodies raised against an oligopeptide having a partial sequence specific for the beta II PKC. The beta II PKC immunoreactivity was widely but discretely distributed in the brain. The distribution of the beta II PKC immunoreactivity differed from that of the beta I and gamma PKC subspecies. The beta II PKC immunoreactivity was found in the perikarya, dendrites, and axons of neuronal cells. Few if any glial cells were stained. Immunoreactive neurons were present in the anterior olfactory nucleus, olfactory tubercle, amygdaloid complex, caudate-putamen, accumbens nucleus, claustrum, dorsal part of the lateral septal nucleus, CA1 region of the hippocampus, subiculum, medial habenular nucleus, cerebral cortex, nucleus of the spinal tract of the trigeminal nerve, nucleus of the solitary tract, and substantia gelatinosa of the spinal cord. In these neurons, the beta II PKC immunoreactivity was seen mainly in the form of cytoplasmic dots and, in some cases, diffusely in the cytoplasm. Under electron microscopy, these immunoreactive large dots appeared to be associated with the Golgi complex, suggesting that the beta II PKC plays a specialized function at the Golgi complex in certain neuronal cell types.

Animals↗

Paraventricular nucleus lesions attenuate the development of hypertension in DOCA/salt-treated rats.

To determine whether paraventricular nucleus (PVN) can play a role in the hypertension in DOCA/salt-treated rats, DOCA/salt hypertension was produced in PVN lesions and sham-operated rats. In lesioned rats, the development of hypertension was significantly attenuated (day 7: 132 +/- 3 v 157 +/- 5 mm Hg, P less than 0.01; day 14: 132 +/- 3 v 157 +/- 5 mm Hg, P less than 0.01; day 21: 189 +/- 2 v 224 +2- 6 mm Hg, P less than 0.01). Lesions lowered systolic blood pressure in even control rats. Mean blood pressure (mBP) from awake free moving rats was also significantly lower in lesioned DOCA/salt-treated rats than those of sham-operated DOCA/salt-treated rats (155 +/- 14 mm Hg v 193 +/- 13, P less than 0.01), while mBP was not different between lesioned and sham-operated control rats. The reduction of mBP by hexamethonium injections was significantly larger in sham-operated DOCA/salt-treated rats than those of lesioned DOCA/salt rats. (-53 +/- 3% v -45 +/- 2, P less than 0.05). Plasma norepinephrine and epinephrine were significantly elevated in DOCA/salt-treated rats, however, PVN lesions inhibited significantly those elevations. 1-Deaminopenicillamine, 4-valine, 8-D-arginine Vasopressin (dPVDAVP) injections did not affect BP and heart rate in all rats. Body weight, water intake, urine volume, urine Na, K, and vasopressin excretion, and urine osmorality were not altered by lesions. These findings suggest that PVN contributes to development of hypertension in DOCA/salt-treated rats with sympathetic nervous activations.

Animals↗

Transection of aortic depressor nerve fails to raise blood pressure in spontaneously hypertensive rats.

Although central resetting via the aortic depressor nerve (ADN) has been known to occur in spontaneously hypertensive rats, the function of the ADN is not yet clear in these animals. To determine whether a baroreflex via the ADN can act to regulate blood pressure during hypertension, blood pressures were measured following ADN transection in spontaneously hypertensive and normotensive rats, and the reflex changes of heart rate and the sympathetic nerve activity were recorded during the pressor response to phenylephrine infusions. Blood pressures were significantly raised 1 day after ADN transections in normotensive rats and continued so for 7 d. Blood pressures were not changed in sham operated rats. In spontaneously hypertensive rats, ADN transections did not alter blood pressures in comparison with sham operated controls. On the seventh day after transections, all rats were anaesthetised with urethane and pressor responses to phenylephrine were examined. Bradycardic and sympathoinhibitory responses to the elevation of blood pressure caused by phenylephrine infusions were significantly smaller in ADN transectioned normotensive rats than in sham operated controls. In spontaneously hypertensive rats, the bradycardic and sympatho-inhibitory responses were not reduced by ADN transections. These findings suggest that the impaired baroreflex via the ADN can contribute to the development of hypertension in the spontaneously hypertensive rat.

Animals↗

Endotoxic properties of chemically synthesized lipid A analogs. Studies on six inflammatory reactions in vivo, and one reaction in vitro.

Biological activities of two groups of synthesized lipid A analogs, the counterpart of biosynthetic precursor, Lehmann's Ia type, 406, and E. coli lipid A type, 506, as well as their non-phosphorylated, and mono-phosphorylated analogs were investigated. The activities employed included four bone marrow cell reactions in mice, mice skin reaction, leukocytes migration in rabbits' cornea, and hemagglutination. Compound 406 and 506 elicited bone marrow reactions in mice and hemagglutination of mouse RBC, although 406 failed to elicit hemorrhage and necrosis also in mice skin. Compound 406 did not elicit corneal reaction in rabbits. The results suggest that for elicitation of this reaction and mice skin reaction, acyloxyacyl structure is required. Cytotoxicity and thromboplastin production of four bone marrow reactions had been reported by us to be endotoxic reactions, since these had not been elicited by peptidoglycan of Lactobacillus and Staphylococcus (1981) and 300 series synthesized analogs (1984) which did not have endotoxic structures. From these results, it seems that these two marrow reactions and hemagglutination require, as does the limulus test, the lipid A part structure as is present in 406.

Animals↗

Chemical structure and toxicity of diuretics in isolated hepatocytes.

The effects of several diuretics, including tienilic acid and indacrinone, on isolated rat heaptocytes were examined. Addition of tienilic acid and indacrinone at 1 mM to a suspension of freshly isolated cells caused dose-dependent loss of cell viability as judged by the LDH-latency test. Survey of 19 structurally related compounds revealed that the extent of cell injury and chemical structure were correlated, and an intense adverse effect was attributed to the 2-thienylcarbonyl moiety. Several other factors influencing cell viability are also disclosed. Further study revealed that tienilic acid and indacrinone were toxic to the primary culture of hepatocytes at a lower dose than that a freshly isolated hepatocytes. Thus, an isolated hepatocyte system can be used to select compounds displaying low hepatotoxicity, as for example is needed when screening diuretics.

Animals↗

Immunocytochemical localization of creatine kinase M in canine myocardial cells: most creatine kinase M is distributed in the A-band.

The localization of creatine kinase (CK) M in canine myocardium was immunocytochemically studied by a direct immunoperoxidase method. Specific antiserum against CK-M was produced in rabbits immunized with canine CK-MM. An anti-CK-M Fab'-horseradish peroxidase conjugate was prepared by the maleimide method. Frozen sections prepared from fixed canine myocardium were stained with the conjugate and observed by light and electron microscopy. In light microscopy of longitudinal sections, CK-M showed a cross-striated pattern consisting of distinct broad and narrow brown bands. Immunoelectron microscopy revealed that the regions of the broad and narrow brown bands corresponded to the A-band and the Z-line, respectively. Most CK-M in the A-band was associated with the thick fibers, and a small amount of CK-M was found in the M-line. These findings suggest that ATP regeneration from the ADP produced by myosin ATPase is related to the participation of this CK associated with the thick fibers rather than that of the M-line-bound CK. Creatine kinase M was also found in the sarcolemmal membrane, the membranes of the sarcoplasmic reticulum, and the mitochondrial outer and inner membranes. This report provides new information for understanding the physiological role of the phosphorylcreatine shuttle in the myocardial energy transport system.

Animals↗

Central baroreflex regulation by the renal nerves in anesthetized rats.

To determine whether the renal nerves affect central baroreflex regulation, the aortic depressor nerve (ADN) was stimulated electrically, while blood pressure, heart rate, and splanchnic nerve activity were recorded in renal denervated and sham-operated rats anesthetized with urethane. Tail cuff systolic pressure fell 6 days after renal denervation, but mean blood pressure recorded after anesthetizing with urethane did not differ between renal denervated and sham-operated rats. Urinary sodium excretion was greater in renal denervated than in sham-operated rats. ADN stimulation produced frequency-dependent falls in blood pressure accompanied by inhibitions of sympathetic nerve activity and heart rate. Depressor and sympathetic inhibitory responses to ADN stimulation were significantly smaller in renal denervated than in sham-operated rats. These findings suggest that the renal nerves can regulate baroreflexes centrally.

Anesthesia↗