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Biomedical subjects

S Hashimoto

Publications and source records attributed to S Hashimoto.

At least 127 records · Page 7Linked to original sources

[Clinical efficacy of Z-100 for the treatment of leukopenia caused by radiotherapy--a multi-center double-blind comparative study with L-cysteine].

The clinical usefulness of Z-100 (Z group) for the treatment of leukopenia caused by radiotherapy for malignant tumors was evaluated by comparing it with that of L-cysteine (L group) by the double-blind method. For 178 complete cases, there were no significant differences in the time-course of the WBC during radiotherapy between the two group. However, for cases with a large field of irradiation (15 X 15 cm = 225 cm2), the mean WBC count in the L group decreased more than that in the Z group. The Z group showed comparable or superior efficacy for the treatment of leukopenia in the L group although there were no significant differences. Adverse reactions were observed in 5.66% and 2.94% in the Z and L groups, respectively, without any significant difference between the groups. The utility rate, useful or better, was 73.9% and 69.2% in the Z and L groups, respectively, showing a slightly higher rate in the Z group than in the L group, although the difference between the two groups was not significant. These results confirmed that Z-100 has comparable or superior efficacy to L-cysteine for the treatment of leukopenia caused by large field radiotherapy for malignant tumors.

Adjuvants, Immunologic

Biological and immunological properties of human hepatocyte growth factor from plasma of patients with fulminant hepatic failure.

We have recently purified human hepatocyte growth factor (hHGF), a heterodimer with molecular weight of about 83,000, from plasma of patients with fulminant hepatic failure (Gohda, E. et al., J. Clin. Invest. 81, 414-419, 1988). Biological and immunological properties of hHGF were examined. Out of the well-known growth factors tested, only epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) stimulated DNA synthesis of adult rat hepatocytes in primary culture. hHGF enhanced the DNA synthesis at less than one-tenth of the molar concentrations of EGF and TGF-alpha. Half-maximal stimulations by hHGF, EGF and TGF-alpha were observed at 30, 400 and 900 pM, respectively. Maximal stimulation by TGF-alpha, however, was greater than those caused by hHGF and EGF. The effect of hHGF was additive with the maximal effects of EGF and TGF-alpha. Anti-hHGF antiserum was prepared in a rabbit by injecting with purified hHGF. This antiserum recognized nonreduced hHGF, but not reduced hHGF. The antiserum for hHGF did not inhibit growth-promoting activity of EGF, that was neutralized by incubation with anti-EGF antiserum. The activity of hHGF was completely inhibited by anti-hHGF antiserum, but not by anti-EGF antiserum. hHGF did not show any cross-reactivity to anti-EGF antiserum as measured by enzyme immunoassay for EGF. Thus, biological and immunological properties of hHGF are different from those of EGF and TGF-alpha.

Animals

[Brachytherapy of prostatic carcinoma, 60Co high dose rate, remote after-loading methods].

Six patients with prostatic carcinoma, including 2 with Stage B, 2 with Stage C, 2 with Stage D1, received transurethral irradiation (TUI) using 60Co high dose rate, remote afterloading methods, in combination with external irradiation by 4 MV X-ray. Total tumor doses were 97.0 to 129.3 in TDF and needle biopsy performed 3 mo after the treatment proved to be free of cancer cell in 5 patients and almost no viable cancer cell in one patient. No adverse reactions were encountered in any patient. We believe that TUI is a useful treatment for prostatic carcinoma.

Aged

Bifurcation of P9 far-field potentials induced by changes in the shoulder position.

Somatosensory evoked potentials to stimulation of the left median nerve were recorded from normal adults with reference to the right knee in the usual shoulder position and in an elevated shoulder position. A single peak of the P9 potentials in the former position bifurcated into two peaks in the latter position without changing the onset latency. This waveform change can be accounted for by changes in the resistance of the volume conductor around the nerve trunk.

Adult

Pulmonary aspergillosis due to Aspergillus terreus combined with staphylococcal pneumonia and hepatic candidiasis.

A female patient with systemic lupus erythematosus (SLE) developed pulmonary aspergillosis with staphylococcal pneumonia and hepatic candidiasis. Aspergillus terreus, which is a rare causative organism of pulmonary aspergillosis, was identified from a pulmonary lesion by culture. The aleurioconidium production, a characteristic of the genus Aspergillus sect. terrei, was demonstrated on short and irregular hyphal features in tissue sections. This report is the first of a combined case of pulmonary aspergillosis due to A. terreus with infections caused by other microorganisms.

Adult

Bone scanning in patients with pleural effusion--experience in 76 cases.

Seventy-six patients with malignant or benign pleural effusion were studied to determine the incidence of accumulation of 99mTc-MDP in relation to effusion, and reveal the mechanism. Of 76 patients, 46 (61%) were found to have diffuse uptake of 99mTc-MDP in the hemithorax, with almost the same positive rate in malignant and benign effusions, i.e. 62% and 57%, respectively. Of 46 patients, 32 (70%) showed diffuse, slight accumulation in the hemithorax, and the positive rate had a tendency to be higher with the increase in the effusion volume. We are convinced that the major mechanism of unilateral intrathoracic accumulation of 99mTc-MDP in pleural effusion is a passive transudation.

Adult

Effects of zinc oxide-eugenol on leucocyte number and lipoxygenase products in artificially inflamed rat dental pulp.

The number of leucocytes and level of endogenous LTC4 in the pulp tissue were measured by a histological method and radioimmunoassay, respectively. When the mandibular incisor pulp was irritated by drilling a hole in the dentine without using any coolant, the number of polymorphonuclear leucocytes and lymphocytes and the concentration of LTC4 increased to 3.2, 1.9 and 1.8 times their respective levels in normal pulp 6 h after the injury. The total leucocyte number in blood collected from these rats was also increased significantly. In contrast, when the cavities cut in dentine were filled with a zinc oxide-eugenol mixture (powder: liquid 100 mg/25 microliters), the increase in the number of cells was significantly curtailed, and the LTC4 level fell to 50% of that in normal pulp within 1 h after the filling. No decrease in the LTC4 level was observed after filling with a zinc oxide-water mixture, but the level decreased in response to an increase in eugenol content in the zinc oxide-eugenol placed in the cavity. Biosynthesis of [14C]-HETE and HPETE from [14C]-arachidonic acid was inhibited by the addition of 10 microM eugenol to the pulp homogenate. Thus eugenol released from zinc oxide-eugenol inhibited the biosynthesis of lipoxygenase products and the early chemotactic accumulation of leucocytes.

Animals

Clearance of argininosuccinate synthetase from the circulation in acute liver disease.

Argininosuccinate synthetase is an enzyme which has been found to be a specific marker for liver damage. In patients with acute hepatitis, the concentration in serum increases at the onset of the disease, but later decreases more quickly, so that the time required for normalization is shorter than that of alanine aminotransferase. This is probably caused by rapid clearance of argininosuccinate synthetase from the serum. Rapid clearance was demonstrated in experimental animals given purified enzymes intravenously. Argininosuccinate synthetase disappeared from the serum with a half life of about 15 min, while the half lives of alanine aminotransferase and aspartate aminotransferase were 4 and 5 h, respectively, under the same conditions.

Acute Disease

Subacute dementia with necrotising encephalitis selectively involving the fornix and splenium. Retrograde development of Alzheimer's neurofibrillar tangles in the subiculum.

An elderly woman developed subacute progressive dementia with predominant impairment in recent memory and CT findings indicating an enhancing lesion near the splenium of the corpus callosum. Autopsy four months after the onset of the symptoms revealed necrotising encephalitis selectively involving the bilateral fornices and the adjacent splenium. Degeneration was marked in the contiguous right fimbria hippocampi. Particularly numerous Alzheimer's neurofibrillar tangles (NFTs) were present in the right subiculum, while they were scattered in Sommer's sectors and parahippocampal gyri and were practically nonexistent elsewhere. Senile plaques were rare. Electron microscopy disclosed that the right subicular tangles were composed mostly of 15-nm straight tubules which were also frequently observed in the myelinated axons. Since the major projection fibers to the fornix originate in the subiculum, the distinctive pattern of NFT distribution might be derived from the retrograde neuronal changes secondary to the fornix-fimbria lesion. This case represents a rare form of amnesia-dementia confirmed anatomically to have been caused by fornix lesions.

Aged

A radioimmunoassay of bile acids.

A radioimmunoassay for beta-muricholic acid was developed using an antiserum which was prepared by injecting beta-muricholic acid conjugated with bovine serum albumin into rabbits. The antiserum reacted with glyco-beta-muricholic, tauro-beta-muricholic and beta-muricholic acids, but not with other bile acids. The radioimmunoassay showed good reproducibility with inter- and intra-assay coefficients of variations of 6% to 15%. When the validity of the method was examined by comparing it with a gas-liquid chromatography method, a linear correlation was obtained.

Animals

Effects of circulating antigen on monoclonal antibody localization.

The potential effects of free circulating antigen on the ability of monoclonal antibodies to target tumors in vivo were investigated. Tumor models consisted of HCC, NuE and PLC cell lines producing AFP xenografted in nude mice, and the NuE-treated mouse designated as the NuE-bearing mouse injected with AFP prior to the administration of antibody. Immunoscintigraphy and biodistribution were evaluated by using 125I-labeled monoclonal antibody 19F12 raised against AFP. Gel chromatography analysis of plasma from the PLC-bearing mouse which excreted 400 ng AFP/ml in blood injected with 125I-19F12 indicated that all injected antibody 19F12 formed an immune complex in plasma. No immune complex was present in plasma from the NuE-bearing mice, where blood AFP levels were 7 ng/ml, while the intact antibody was found to remain partly in plasma from the NuE-treated mouse. Radioactivities in the whole body of NuE-bearing and NuE-treated mice eventually cleared at the same rate. Our experimental results indicated that the endogeneous circulating antigen retained the antibody in the whole body for a longer period. The ability of monoclonal antibodies to target tumors was influenced not only by how much antigen was present but also by how rapid the antigen was cleared in the blood.

Animals

Volume conduction of the parietal N20 potential to the prerolandic frontal area.

Somatosensory evoked potentials were recorded from the frontal and parietal areas in patients with various lesions in the central nervous system on stimulation of the median nerve. Five representative cases who showed a selective loss of the positive potential from the frontal area are reported. In each case, the parietal N20 potential was relatively well preserved, and the midposition between the frontal and central areas (FC area) showed a negative potential following P14. The peak of this negative potential was synchronous with that of the parietal N20 potential. This negativity on the FC area is considered to be a volume conducted potential from the parietal N20 to the prerolandic frontal area. Such an anterior volume conduction of the parietal N20 would not be explained by the concept of a tangentially oriented dipole generated in the posterior bank of the central sulcus. Instead, for the generator of the parietal N20 potential, a radically oriented dipole generated mainly in the parietal area is postulated.

Adolescent

Mechanism of a lymphocyte abnormality associated with HLA-B8/DR3: role of interleukin-1.

Lymphocytes from normal individuals with the histocompatibility antigens HLA-B8 and DR3 have impaired proliferative responses when stimulated with suboptimal concentrations of mitogens. We have previously shown that an important factor in the impaired response is a failure to produce normal quantities of interleukin-2 (IL-2). To examine the mechanism of decreased responsiveness further, we measured interleukin-1 (IL-1) production of low responder subjects compared with controls. The peripheral blood mononuclear cells of five low responder individuals with HLA-B8/DR3 stimulated with 0.05 micrograms/ml of phytohaemagglutinin (PHA) accumulated only 0.036 U/ml of IL-1 compared with 0.32 U/ml for normal responders. There was a highly significant correlation between the PHA-stimulated IL-1 concentration at 12 h and the subsequent IL-2 concentration at 48 h(r = 0.89, P less than 0.0001) suggesting a role of decreased IL-1 production in the impaired response. A study of unfractionated or column-fractionated culture supernatants revealed no evidence that the decreased IL-1 activity in the supernatants of low responder subjects was related to increased IL-1 inhibitor concentrations. These results suggest that impaired IL-2 production and lymphocyte proliferation in healthy subjects with HLA-B8/DR3 may be mediated at least in part by decreased IL-1 production, and implicates a defect of a very early event in lymphocyte activation.

Adult

Morphological estimation of brain extracellular fluid dynamics in cold-induced edema from the aspect of cerebrospinal fluid-extracellular fluid communication.

Following the induction of cold injury in the parietal cortex of rats, the brain extracellular fluid dynamics under conditions of cryogenic edema were investigated morphologically from the aspect of extracellular fluid (ECF)-cerebrospinal fluid (CSF) communication using horseradish peroxidase (HRP) injected into the cisterna magna as a marker. About 24 h after the induction of cold injury, HRP was distributed in the subjacent white matter of the lesion and around the ventricle. Forty-eight hours after injury, the distribution of HRP around the lesion became distinctive. This distribution of HRP became more concentrated at the same location on day 3-4 after injury. At this time, HRP was observed to be distributed along the walls of small vessels, in the cytoplasm of a few neurons and in the neuropil around the lesion by light microscopy. At small vessels around the lesion, a dense deposit of HRP at the basement membrane and many abluminal vesicles were evident by electron microscopy. These findings indicate that ECF-CSF communication changes drastically under the influence of edema fluid dynamics. In particular, the dense distribution of HRP around the lesion on day 3-4 after injury can be attributed to active retrograde transport by vessels in this area, a phenomenon considered important for edema resolution.

Animals

Nerve growth factor-induced transient increase in the phosphorylation of ribosomal protein S6 mediated through a mechanism independent of cyclic AMP-dependent protein kinase and protein kinase C.

Treatment of PC12h cells with nerve growth factor (NGF) induced a transient increase in the phosphorylation of a 35,000-dalton protein. This transient increase was observed also when extracts of NGF-treated cells were incubated with [gamma-32P]ATP. In the intact-cell phosphorylation system, treatment with N,2'-dibutyryladenosine 3',5'-cyclic monophosphate (dBcAMP) or 12-O-tetradecanoylphorbol 13-acetate (TPA) also induced a transient increase in the phosphorylation of the 35,000-dalton protein, but the effect was less than that of NGF. An effect comparable to that of NGF was obtained by the combination of dBcAMP and TPA. Pretreatment of PC12h cells with dBcAMP plus TPA for 3 days, which deprived the cells of their ability to respond to a rechallenge with dBcAMP, TPA, or dBcAMP plus TPA by increasing the rate of 35,000-dalton protein phosphorylation, caused only a slight attenuation of the NGF effect, directly indicating a minimal role of cyclic AMP (cAMP)-dependent protein kinase and protein kinase C in the mechanism of the NGF action. Pretreatment of the cells with K-252a, a protein kinase inhibitor, at a concentration of 300 nM almost completely blocked the action of NGF, but scarcely affected the action of dBcAMP, TPA, or dBcAMP plus TPA in intact-cell phosphorylation experiments. This NGF-sensitive 35,000-dalton protein was a ribosomal protein and identified as ribosomal protein S6. The results lead us to conclude that NGF activates some NGF-sensitive component(s), probably some specific protein kinase(s) other than cAMP-dependent protein kinase or protein kinase C, which is suppressed by K-252a and directly or indirectly activates a 35,000-dalton protein kinase(s) [S6 kinase(s)] to increase the rate of phosphorylation of the 35,000-dalton ribosomal protein (S6).

Adenosine Triphosphate