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Biomedical subjects

I Hashimoto

Publications and source records attributed to I Hashimoto.

At least 163 records · Page 9Linked to original sources

Ultrastructural studies on the pathogenesis of poliomyelitis in monkeys infected with poliovirus.

Poliovirus was inoculated intraspinally into cynomolgus monkeys to determine whether nerve cell damage in the central nervous system (CNS) is due primarily to virus multiplication in the neuron or to secondary effects of virus multiplication in the supporting cells. Electron-microscopically, the development of cytopathogenesis and of membrane-bound vesicles and virus particles in the neurons of the CNS in monkeys infected with poliovirus was compared with that of infected cultured cynomolgus monkey kidney (CMK) cells. The structure of membrane-bound vesicles in cytoplasm of damaged motoneuron was examined and found to be similar to the vesicles in infected cultured CMK cells. Virus-like particles were detected occasionally around or within membrane-bound vesicles in the cytoplasm of degenerating motoneurons as well as cultured CMK cells, although intracytoplasmic crystals were not detected in the neuron. No virus particles or membrane-bound vesicles were found in astrocyte foot plates, microglia, oligodendrocytes, axons, vascular endothelial, and inflammatory cells. In addition, poliovirus antigen was detected only in the nerve cells of the CNS by the immunoperoxidase technique, although specific staining was never found in the supporting tissues. From the present results we suggest that membrane-bound vesicles in the cytoplasm of the motoneuron are closely correlated with virus multiplication and that damage of the nerve cell is due to the direct action of the poliovirus.

Animals

Genetic and phenotypic characteristics of enterovirus 71 isolates from patients with encephalitis and with hand, foot and mouth disease.

Biological and biochemical characters of seven enterovirus 71 (E71) isolates were compared. Four isolates (two from patients with hand, foot and mouth disease [HFMD] and two from patients with encephalitis) grew in cynomolgus monkey kidney cells both at 39.5 and 35 degrees C. However, the remaining three strains (from patients with HFMD) grew at 35 degrees C, but not at 39.5 degrees C. Three temperature-resistant and two temperature-sensitive strains were tested for neurovirulence in monkeys. Temperature-resistant strains were shown to be neurovirulent, whereas temperature-sensitive strains were less neurovirulent. The results suggest correlation between temperature-sensitive growth and neurovirulence in monkeys of E71. Variation in the electrophoretic mobility of the viral polypeptides was detected in three out of seven strains. The fingerprinting of oligonucleotides generated from the viral genome showed similar patterns in two isolates from patients with HFMD and one from patient with encephalitis and variable patterns in each genomic map of remaining four strains. These variations of polypeptide patterns and of oligonucleotide maps could not be correlated with pathogenicity (encephalitis or HFMD), temperature-sensitive growth and neurovirulence in monkeys.

Animals

The role of the spleen in tumor bearing host: I. Characterization of spleen cells in tumor-bearing mice.

Morphologic changes of the spleen and dynamic changes of biologic activity of spleen cells from C3H/HeJ mice bearing methylcholanthrene induced fibrosarcoma (MCA-F) were investigated in different stages of tumor growth, using local adoptive transfer assay (LATA). The spleen size, weight and the number of spleen cells increased with the tumor growth. In early and late stages of tumor growth, tumor-bearing mice possessed non-specific tumor-enhancing cells which were radioresistant (700 rads), phagocytic and adherent, suggesting that they were macrophages. On the other hand, in middle stages of tumorgenesis, tumor-bearing mice possessed specific cytotoxic cells which were radiosensitive (700 rads) and anti-Thy 1.2 serum positive, suggesting that they were T-cells. Thus, the appearance of tumor-enhancing cells was earlier than cytotoxic cells in MCA-F bearing host, and the balance of tumor-enhancing and cytotoxic cells may influence the tumor outgrowth in different stages of tumorgenesis. The spleen serves as a reservoir of factors which either abrogate cell mediated resistance or stimulate neoplastic growth, or as the source of cytotoxic cells, at certain times of tumor burden.

Animals

The role of the spleen in tumor bearing host: II. The influence of splenectomy in mice.

The effect of splenectomy on neoplastic outgrowth was examined prior to and after implantation of methylcholanthrene-induced C3H/He murine tumors. Splenectomy performed 12 days before tumor inoculation did not affect the tumor outgrowth, however, both splenectomy and sham operation performed shortly before tumor inoculation resulted in significant tumor facilitation compared with the non-operated group, suggesting that this accelerated tumor was not related to the presence or absence of splenic tissue, but rather to systemically-induced immunosuppression. While splenectomy performed 6, 9, 12 days after tumor inoculation did not alter the tumor growth, splenectomy performed early (3 days) or late stage (20 days) after tumor cell challenge revealed a retarded neoplastic outgrowth, compared with the sham operated group. These results suggest that splenectomy in very early and late stages of tumor-bearing host may be effective for tumor treatment.

Animals

Somatosensory evoked potentials from the human brain-stem: origins of short latency potentials.

Short latency somatosensory evoked potentials (SEPs) were recorded in man from an array of electrodes within the IVth (the pons) and IIIrd ventricles (the thalamus) and the aqueduct of Sylvius (the midbrain). The slow negative (N15 and N20) and positive (P22) waves were preceded by 4 small positive (P9, P11, P13, and P14) waves by approximately 1 msec duration in scalp recordings. The sources of these waves have been differentiated on the basis of their timing and spatial gradients of corresponding intracranial potentials. While P11 is identified as volume conducted from below the brain-stem, P13 and P14 reflect synchronized volleys of the medial lemniscus and its branches to the various pontine and mesencephalic nuclei. In contrast to these earlier positive wavelets arising from fiber tracts, N15 may represent postsynaptic activities within these pontine and midbrain nuclei. N20 and P22 are the initial responses of the juxtarolandic cortex.

Brain Stem

Completely thrombosed giant aneurysm of the angular artery.

An unusual case of a completely thrombosed giant aneurysm arising from the angular artery is reported. A 69-year-old women developed a subarachnoid hemorrhage with a large intracranial hematoma. Computed tomography scans and cerebral angiography could not detect the aneurysm. The rarity of aneurysms in this position is stressed and the difficulty of diagnosis in this case is discussed.

Aged

Effect of exercise training on plasma high-density lipoprotein cholesterol level at constant weight.

Previous investigations have demonstrated an increase of plasma high-density lipoprotein cholesterol (HDL-Chol) and a decrease in the ratio of low density lipoprotein (LDL)-Chol/HDL-Chol (Atherogenic Index; AI) as a result of exercise training. The question of whether elevation of HDL-Chol was a consequence of weight reduction or physical training itself was unsolved. The present study was designed to prevent the weight reduction that is associated with exercise training. Five healthy and mildly active male volunteers, aged 28-31 years, participated in a 4-week training programme. They ran on a treadmill at 140-160 m/min at 0% grade for 50 min, 5 times a week, equivalent to an energy expenditure of 9 kcal/kg body weight/day. Subjects maintained their body weights by increasing calorie intake to match increased energy expenditure. No changes were observed in mean body weight, skinfold thickness, basal metabolism, and maximal oxygen uptake after the training programme. The HDL-Chol level increased from 54 to 73 mg/dl (P less than 0.05), and the reduction of AI was 30.8% (P less than 0.05) in response to the exercise training. However, the exercise training did not induce changes in plasma total cholesterol and triglyceride (TG) levels. The results of this experiment suggested that moderate physical training itself can be a potent factor for the regulation of HDL-Chol level and improvement of the AI in the absence of alterations in body weight.

Adult

[Effect of anabolic steroid on immune response].

Using lymphocyte, monocyte and eosinophil counts of the peripheral blood, PHA-blastoid transformation, immunoglobulin and beta 2-microglobulin, the influence of anabolic steroid on the immune reactivity of the host was dissected by administration of Deca-Durabolin ( nandrolone decanoate) to both tumor-bearing host and tumor-free host after operation for alimentary tract. The number of peripheral lymphocytes and monocytes, the PHA-blastoid transformation of peripheral lymphocytes and the IgG level were increased, and the beta 2-microglobulin level showed the tendency of decrease after the administration of Deca-Durabolin.

Female

[5-Fluorouracil concentration in various tissues from cancer patients after oral administration of 5-fluorouracil].

5-Fluorouracil(5-FU)is a widely used antitumor agent for treating patients with adenocarcinoma of gastroenterial tract and breast following intravenous or oral administration. The blood level of 5-FU peaked rapidly after intravenous bolus injection and then decreased in a short time, disappearing 90 minutes after injection. But the blood level of 5-FU peaked from 15 to 30 minutes after oral administration of 5-FU tablets or dry syrup and decreased slowly, frequently showing 0.02 microgram/ml at 120 minutes after oral administration. In cancer chemotherapy, a tissue drug concentration is represented by its serum level in practice, generally because of the difficulty in determining the tissue drug level of the patients. This study was performed to determine the tissue 5-FU level after oral administration of 5-FU. Before surgery, 400 to 600 mg of 5-FU tablets was orally administered to 13 patients including 5 cases of gastric, 5 of breast, 1 of colon and 2 of other types of cancer. Tissue specimens of different sites and serum samples were obtained during the operation: cancer tissues, normal gastric or colon wall, normal breast, lymph nodes and subcutaneous fatty tissues, etc. The materials were frozen immediately at -20 degrees C and sent to Pharmaceutical Research Laboratories, Fuji Plant, Kyowa Hakko Kogyo Co., Ltd. ( Nagaizumimachi , Shuntogun , Shizuoka , Japan). The materials were assayed for 5-FU by bioassay method using Staphylococcus aureus 209P or Micrococcus flavus ATCC 10240 as the test organisms. The 5-FU concentration in mastopathy tissue was traced to all of the agents at 20 to 180 minutes after 400 mg of 5-FU was administered orally in tablet form. 5-FU concentrations in gastric cancer tissues ranged from 0.30 to 1.30 micrograms/g at 163 to 235 minutes after administering 600 mg of 5-FU tablets, whereas in normal gastric wall were much lower than in gastric cancer tissues. That in the breast cancer tissues was 0.042 to 0.12 microgram/g at 100 to 240 minutes after oral administration. 5-FU was maintained at a higher concentration in cancer tissues for a long time, while the serum concentration decreased to trace amounts. 5-FU in non-cancerous tissues was invariably traced in most patients as mastopathy tumors. From the above results, 5-FU tablets proved to be a useful drug in cancer chemotherapy.

Adenocarcinoma

Comparative studies on the neurovirulence of temperature-sensitive and temperature-resistant viruses of enterovirus 71 in monkeys.

The neurovirulence of strain BrCr of enterovirus 71 (E71) was compared in monkeys between temperature-sensitive (ts) and temperature-resistant (tr) viruses. Comparisons are made relative to clinical disease, pathologic findings, serum neutralizing antibody titers, CNS virus replication as measured by infectivity titrations and immunofluorescence. Clinically, ts virus did not produce a clinical disease. The tr virus, however, produced paralysis. Pathologically, little or no nerve cell damage was found in the CNS of monkeys inoculated with ts virus, although mild to moderate interstitial changes occurred. In monkeys inoculated with tr virus, marked nerve cell damage and inflammatory reaction were found in the CNS. Serum neutralizing antibody titers in monkeys inoculated with ts virus rose on day 25. No virus was detected in the CNS of monkeys inoculated with ts virus, while a high virus titer was detected in the CNS of monkeys inoculated with tr virus. No specific immunofluorescence was detected in the nerve cells of the CNS in monkeys inoculated with ts virus, but specific fluorescence was detected in the nerve cells of the CNS in monkeys inoculated with tr virus. Virus growth in the CNS correlated well with the severity of clinical and pathologic findings, and immunofluorescent studies. The results show that ts virus was much less neurovirulent than tr virus, indicating that ts virus resembles the attenuated poliovirus which could not grow at a higher temperature. It is inferred that the genetic factors which influence the reproductive capacity of E71 at a higher temperature are very closely correlated with the neurovirulence.

Animals

Spontaneous blastogenesis assay for detection of renal allograft rejection in man.

In attempts to assess the possibility of allograft rejection, serial assays of spontaneous blastogenesis (SB) by uptake of tritium thymidine in 50 microliters whole blood were performed in 72 consecutive renal allograft recipients. Of 79 clinically diagnosed rejection episodes, 65 (82 per cent) had an associated elevation of SB values, and 14 (18 per cent) showed false negative results. In 38 (59 per cent) of 65 episodes in which the elevations of SB values were observed, the elevations preceded the clinical diagnosis by 1-7 days. Although large doses of steroids did not affect the values of SB, false positive elevations which were mainly caused by systemic infections occurred in 12 cases. There was no significant association between severity of rejection crisis and the maximum value of SB in the course. The SB assay requiring only a small amount of blood can be accomplished within 4-5 hours and provides a simple means of assessing and predicting host's immune responsiveness to the histocompatibility antigens.

Graft Rejection

Analysis of data on 170 consecutive patients transplanted with kidneys from living relatives.

Graft survival, mortality, histocompatibility and rehabilitation were studied in 170 consecutive patients receiving kidneys from living relatives. Average follow-up was 5 years and one month with a minimum post-transplant evaluation of 6 months. Overall patient survival was 93 per cent at one year and there was a remarkable decline thereafter. Overall graft survival was 84 per cent at one year, 73 per cent at three, and 67 per cent at five years. Among the 76 patients treated since 1979, both patients and graft survival have improved: 93 per cent and 80 per cent at three years, respectively, because of a decrease in serious complications. Although no correlation was found between HLA-A and B loci matching and graft survival in patients with no mismatch in the HLA-DR locus, there was a significantly higher graft survival. Infection, the leading cause of death especially in the early post-transplant period, has been brought under control. Aseptic necrosis of the femoral head which occurred in 27 (16 per cent) patients proved to be the most difficult problem. The majority of patients are functioning well socially and vocationally and reproductive functions have been restored. Transplantation offers a better quality of life for patients with chronic renal failure, as compared to hemodialysis. The increased procurement of cadaver kidneys must be given attention.

Adolescent

Isolation of a temperature-sensitive strain of enterovirus 71 with reduced neurovirulence for monkeys.

Small- and large-plaque-producing viruses were selected from the enterovirus 71 (E71) prototype, BrCr. The small-plaque virus was a temperature-resistant (tr) strain which could multiply at 39.5 degrees C as well as 35 degrees C. The large-plaque virus was temperature-sensitive (ts) and could not grow at 39.5 degrees C. It was shown that the ts strain was much less neurovirulent for monkeys than the tr strain. Both tr and ts strains reacted with homologous and heterologous antibodies in cross-neutralization tests. While no difference was found between tr and ts strains in the size of virion polypeptides, the VP1 polypeptide could be differentiated by isoelectric focusing. Genomic differences between the two strains were found by oligonucleotide mapping.

Animals