Search PubMed⌕ Search

Biomedical subjects

J Shimizu

Publications and source records attributed to J Shimizu.

At least 199 records · Page 11Linked to original sources
PubMed1992

[A case of progressive hemiatrophy with type 2 muscle atrophy in muscle biopsy].

We reported a case of progressive hemiatrophy, whose skeletal muscle biopsy revealed type 2 fiber atrophy. This patient, a 40-year-old woman, noticed left leg atrophy at the age of 39. She had a history of minor trauma of the left thigh at the age of 30. On admission, physical examination revealed atrophy of various parts of her left side of body, predominantly in the left leg. There was no dermatological or neurological abnormalities except these atrophies. Hematological and biochemical examinations were normal. EEG, EMG, nerve conduction studies and autonomic function tests were normal in either side of the body. MRI study showed reduced muscle bulk as well as subcutaneous fatty tissue especially in her left leg. Skeletal muscle biopsy of her left quadriceps femoris muscle revealed type 2 fiber atrophy and type 1 fiber predominance. However, no abnormality was found in the intramuscular nerves. We considered that type 2 muscle fiber atrophy was one of the cause of atrophy of this case.

Adult↗
PubMed1992

[Gerstmann-Sträussler-Scheinker disease with heterozygous codon change at prion protein codon 129].

A 53-year-old male was admitted to our hospital for progressive dementia and gait disturbance which had started at the age of 48. Examination indicated dementia, dysarthria, dysphagia, bilateral pyramidal signs, apraxia of the limbs, and extrapyramidal signs such as fine finger tremors, and rigidity of limbs. There were no cerebellar signs or myoclonus. His mother and elder brother showed similar symptoms and died at the ages of 53 and 50, respectively. EEG was normal. CT and MRI showed mild brain atrophy, but no cerebellar atrophy. T2 weighted image indicated low intensity areas covering bilateral caudate nuclei and putamina. A heterozygous amino acid change from methionine to valine was noted at codon 129 of the prion protein of the patient as well as in one of his son. The most likely diagnosis was Gerstmann-Sträussler-Scheinker (GSS) disease without cerebellar atrophy. GSS may include a broad spectrum of brain pathology. Whether the codon change is associated with pathology without cerebellar atrophy is a problem that awaits further investigation.

Atrophy↗
PubMed1992

[XYY syndrome associated with motor neuropathy].

We described a case of XYY syndrome associated with motor neuropathy. The case was a 27-year-old male, who had 47-XYY chromosome karyotype. His symptoms were distal dominant muscle weakness and muscle atrophy in his lower extremities without objective sensory disturbance. He had no mental retardation or family history of neurologic diseases. The electrophysiological and pathological examinations revealed that his symptoms were due to peripheral motor neuropathy (neuronal type). His motor neuropathy may be of sporadic type. There may be some relation in the pathogenesis between XYY syndrome and motor neuropathy, although in the literature, XYY syndrome with motor neuropathy had not been reported so far.

Adult↗
PubMed1991

Heterogenous graft rejection pathways in class I major histocompatibility complex-disparate combinations and their differential susceptibility to immunomodulation induced by intravenous presensitization with relevant alloantigens.

The present study investigates the heterogeneity of graft rejection pathways in class I major histocompatibility complex (MHC)-disparate combinations and the susceptibility of each pathway to immunomodulation induced by intravenous presensitization with alloantigens. Depletion of CD8+ T cells was induced by repeated administration of anti-CD8 monoclonal antibody. CD8+ T cell-depleted mice failed to generate anti-allo class I MHC cytotoxic T cell (CTL) responses but exhibited anti-allo class I MHC T cell responses, such as mixed lymphocyte reaction (MLR)/IL-2 production, that were induced by CD4+ T cells. In contrast, donor-specific intravenous presensitization (DSP), as a model of donor-specific transfusion, induced almost complete elimination of CD4+ and CD8+ T cell-mediated MLR/IL-2 production, whereas this regimen did not affect the generation of CTL responses induced by DSP-resistant elements (CD8+ CTL precursors and CD4+ CTL helpers). Prolongation of skin graft survival was not induced by either of the above two regimens alone, but by the combination of these. Prolonged graft survival was obtained irrespective of whether the administration of anti-CD8 antibody capable of eliminating CTL was started before or after DSP. The combination of DSP with injection of anti-CD4 antibody also effectively prolonged graft survival. However, this was the case only when the injection of antibody was started before DSP, because such antibody administration was capable of inhibiting the generation of CTL responses by eliminating DSP-resistant CD4+ CTL helpers. These results indicate that (a) the graft rejection in class I-disparate combinations is induced by CD8+ CTL-involved and -independent pathways that are resistant and susceptible to DSP, respectively; (b) DSP contributes to, but is not sufficient for, the prolongation of graft survival; and (c) the suppression of graft rejection requires an additional treatment for reducing DSP-resistant CTL responses. The results are discussed in the context of potential clinical application in attempts to inhibit the generation of DSP-resistant CTL responses upon the prospective DSP.

Animals↗
PubMed1991

Heterogeneity of CD4+ T cells involved in anti-allo-class I H-2 immune responses. Functional discrimination between the major proliferating cells and helper cells assisting cytotoxic T cell responses.

MLR in various combinations with class I H-2 disparity revealed that there are three patterns of MLR in the aspect of responding T subset (CD4 vs CD8) dominance. Irrespective of the CD8 vs CD4 dominance, a single i.v. administration of class I-disparate allogeneic spleen cells resulted in almost complete abrogation of anti-class I proliferative capacity of both CD4+ and CD8+ T cells in six combinations. The suppression of proliferative responses was correlated with the striking reduction in the ability to produce IL-2 upon stimulation with the relevant class I alloantigens. In contrast, i.v. presensitized recipient mice exhibiting only marginal MLR/Il-2 production could generate comparable magnitudes of anti-allo class I CTL as well as graft rejection responses to those induced by normal unpresensitized mice. The administration in vivo of anti-CD4 antibody along with the i.v. presensitization not only suppressed the generation of CTL responses by spleen cells but also induced appreciable prolongation of allo-class I-disparate skin grafts under conditions in which neither alone did it. These results demonstrate that 1) the suppression of graft rejection responses is not necessarily reflected on the reduction of MLR; 2) CD8+ CTL precursors responsible for graft rejection can be activated by either allo-class I-reactive CD8+ or CD4+ Th cells; 3) i.v. presensitization induces functional elimination of CD8+ and CD4+ proliferative/IL-2-producing T cells but not of CD8+ CTL precursors and CD4+ Th whose capacity is expressed by assistance of CTL induction but not by their own proliferation. Thus, this study illustrates the heterogeneity of class I alloantigen-reactive CD4+ T cells in the aspect of their capacity to proliferate themselves vs contribute to CTL induction as well as graft rejection.

Animals↗
PubMed1991

Evidence for the functional binding in vivo of tumor rejection antigens to antigen-presenting cells in tumor-bearing hosts.

Spleen cells of BALB/c mice bearing a syngeneic CSA1M fibrosarcoma were treated with anti-Thy-1.2 antibody plus C, yielding a T cell-depleted, APC-containing fraction. The APC-containing fraction was first tested for its capacity to present exogenous modified-self or another tumor (Meth A) Ag after in vitro pulsing. The results showed comparable Ag-presenting capacities to those obtained by APC-containing fraction from normal spleen cells, indicating that APC function is not affected in tumor-bearing mice. We next examined whether APC from CSA1M-bearing mice bind endogenously generated CSA1M tumor Ag onto its surfaces to stimulate tumor-specific T cells. Five rounds of inoculation of APC-containing fraction from CSA1M-bearing mice without further in vitro pulsing resulted in the induction of potent anti-CSA1M immune resistance. The involvement of anti-CSA1M T cells in the induction of anti-CSA1M immunity was excluded by the fact that the in vivo immunity was excluded by the fact that the in vivo immunity was delivered by Thy-1+ cell-depleted, but not by Thy-1+ cell-enriched fractions of spleen cells from CSA1M-bearing mice. Moreover, the failure of Sephadex G10-passed spleen cells to deliver anti-CSA1M resistance demonstrated the absolute requirement of APC for inducing the in vivo immunity. Finally, this in vivo resistance was found to be tumor specific, because APC fractions from CSA1M-bearing and Meth A-bearing BALB/c mice induced immune resistance selective against the corresponding tumor cell challenge. These results indicate that APC from tumor-bearing hosts can not only exert unaffected APC function against exogenous Ag, but also function to present tumor Ag generated endogenously in the tumor-bearing state and to produce tumor-specific immunity in vivo.

Animals↗
PubMed1991

Age-related decreases of the N-methyl-D-aspartate receptor complex in the rat cerebral cortex and hippocampus.

Binding activities of central excitatory amino acid receptors were examined in Triton-treated membrane preparations of the cerebral cortex and hippocampus from brains of rats at 2, 7 and 29 months after birth. Aged rats exhibited a significant reduction of [3H]glutamate (Glu) binding displaceable by N-methyl-D-aspartate (NMDA), as well as strychnine-insensitive [3H]glycine binding in both central structures, as compared with those in young rats. Binding of [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne maleate (MK-801), a non-competitive NMDA antagonist used to label the activated state of ion channels linked to NMDA-sensitive receptors, also decreased with aging irrespective of the experimental conditions employed. Scatchard analysis revealed that reduction of both [3H]Glu binding and [3H]MK-801 binding were due to a significant decrease in the densities of binding sites with aging, with their affinities being unaltered. Binding of [3H]D,L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), which is a specific agonist for quisqualate-sensitive receptors, was unchanged with aging when determined in the absence of 100 mM potassium thiocyanate (KSCN). However, AMPA binding determined in the presence of added KSCN was about 25% reduced in both brain regions of aged rats. Binding of [3H]kainate to kainate-sensitive receptors was unchanged with aging. These results suggest that glutaminergic neurotransmission mediated by NMDA-sensitive receptors may be selectively impaired with aging in the hippocampus and cerebral cortex among 3 different subclasses of excitatory amino acid receptors in the brain.

Aging↗
PubMed1991

Transforming growth factor-beta-induced inhibition of T cell function. Susceptibility difference in T cells of various phenotypes and functions and its relevance to immunosuppression in the tumor-bearing state.

The present study investigates the nature of humoral component(s) generated in tumor-bearing hosts to induce immune dysfunction of T cells. Cell-free ascitic fluid and culture supernatant (SN) were obtained from the ascites and cultures allowing MH134 hepatoma cells to grow. These ascites and SN samples were tested for their abilities to influence the generation of CTL responses to TNP and alloantigens. The generation of the anti-TNP CTL responses that require self H-2-restricted CD4+ Th cells was markedly suppressed by addition of the ascites or SN under conditions in which these samples did not inhibit anti-allo CTL responses capable of using alternate pathways of allo-restricted CD4+ and CD8+ Th. The activation of CD8+ CTL precursors and CTL activity were also resistant to the ascites or SN. The ascites- or SN-induced suppressive effect to which CD4+ Th were most susceptible was found to be mediated by transforming growth factor-beta (TGF-beta) activity, because: 1) the TGF-beta activity was detected in the MH134 ascites and culture SN; 2) the suppression of CD4+ Th function required for anti-TNP CTL responses was almost completely prevented by addition of anti-TGF-beta antibody to cultures and; 3) rTGF-beta also induced similar patterns of immunosuppression to those observed by ascites or SN. These results indicate that TGF-beta produced by tumor cells induces deleterious effects on T cell, especially on the CD4+ Th subset, and provide an explanation for the molecular mechanism underlying the previously observed CD4+ Th-selective suppression in the tumor-bearing state.

Animals↗
PubMed1991

Early hilar lung cancer: its clinical aspect.

Early hilar lung cancers are rare, but are curable if they are properly diagnosed and treated. In the past 14 years, we have treated 27 patients with early hilar cancers that fulfilled the criteria proposed by the Japanese Lung Cancer Society (JLCS). Eighteen patients presented with symptoms and 9 were detected by the mass screening examination of sputum cytology. All lesions in both groups were finally diagnosed by bronchoscopy. Twenty patients (74%) had positive sputum cytology, whereas only 7 (26%) had positive chest X-ray findings. All the patients underwent surgery, and bronchoplasty was the most frequent operative procedure. The 5-year survival rate was 100%, and the 10-year survival rate was 91.7%, as one patient died of a second primary lung cancer in the 6th postoperative year. In conclusion, the definition of early hilar lung cancer proposed by the JLCS is thought to be reasonable, and early hilar lung cancer is a curable disease, if it is properly diagnosed and treated.

Bronchoscopy↗
PubMed1991

Aggressive surgical intervention in N2 non-small cell cancer of the lung.

An aggressive attitude toward surgical treatment was taken in patients with N2 non-small cell lung cancer in the past 10 years. Computed tomographic scanning was employed in the diagnosis of N2 disease, and had a true-positive rate of 57%. Among patients with N2 disease detected by computed tomographic scanning, surgical intervention was attempted except for those with unresectable disease. Of 190 patients with clinical N2 disease, 115 underwent surgical exploration: 9 patients had only an exploratory thoracotomy, 53 patients underwent a curative operation, and 53 had a noncurative operation. The overall 5-year survival rate of these patients was 16% and that of curatively resected patients was 20%. There were 47 patients whose N2 disease was not recognized before operation. The 5-year survival rate of this group was 20% overall and 33% in curatively resected cases. The overall 5-year survival rate of patients with N2 disease who underwent resection (106 with clinical N2 disease and 47 with clinically unrecognized N2 disease) was 17%, and that of the 84 patients undergoing curative operations was 24%. An aggressive attitude toward surgical intervention can be advocated for patients with N2 disease on the basis of our present results.

Carcinoma, Non-Small-Cell Lung↗
PubMed1991

Effects of fetal treatment with methylazoxymethanol acetate on radial maze performance in rats.

Pregnant rats (Wistar-Imamichi strain) were treated with 15 mg/kg/d of methylazoxymethanol acetate (MAM) on days 13-15 of gestation. Nine male rats, which were randomly selected from the MAM-treated offspring (MAM rats), were examined for their spatial recognition ability by the radial maze technique and compared with control offspring. Although the performances of MAM rats were inferior to the control, they could reach the predetermined criterion within 15 trials. Subsequent retention tests revealed the drastic impairment of performance in MAM rats when the retention interval was over 15 min. The total activity of choline acetyltransferase showed a significant decrease in the hippocampus and cerebral cortex of MAM rats. These results suggest that working memory disorders of MAM rats on radial maze tasks may be due to the lowering of cholinergic functions in their hippocampus and cerebral cortex.

Animals↗
PubMed1991

Results of surgical treatment in patients with stage IIIA non-small-cell lung cancer.

From 1973 to 1989, surgical resection was performed in 235 stage IIIA non-small-cell lung cancer patients (78% of all admitted stage IIIA patients). Complete resection was accomplished in 155 patients and 80 underwent incomplete resection. The rate of incomplete resection was higher in patients with adenocarcinoma than in those with squamous cell carcinoma. There were 7 operative deaths (2.8%) among the patients undergoing operation. The five-year survival rate of the group having complete resection was 32%, whereas that of the incomplete resection group was 5% (p less than 0.05). The five-year survival rate of T3NO-1MO patients with complete resection was 50% and that of T1-2N2MO patients was 30%. However, the five-year survival rate of patients with T3N2MO disease was significantly poorer at 10% (p less than 0.05). The five-year survival rates of patients undergoing complete resection including the combined resection of an adjacent organ were: pericardium 43%; chest wall 43%; pleura 34%; and bronchus 46%. Forty-nine patients survived over three years and 10 of them died between three and five years after surgery, but five-year, four-year, and three-year survivors numbered 29, 4, and 6, respectively. Surgical resection appears to be the treatment of choice for stage IIIA non-small-cell lung cancer whenever complete resection is feasible.

Carcinoma, Non-Small-Cell Lung↗
PubMed1991

Results of surgical treatment in patients with stage IIIB non-small-cell lung cancer.

From 1973 to March 1989, surgical resection was performed in 83 stage IIIB non-small-cell lung cancer patients (81% of all admitted stage IIIB patients). There were 2 operative deaths (2.3%), and complete resection was accomplished in 33 patients. The five-year survival rate of the patients undergoing complete resection was 25%, whereas that of the incomplete resection group was nil (p less than 0.05). Among the 26 patients with invasion of mediastinal structures who underwent complete resection, 3 patients survived for over five years. Two had squamous-cell carcinoma and one had adenocarcinoma, and their tumors involved the left atrium, pulmonary arterial trunk, and superior vena cava, respectively. Among the 6 patients with T4 lesions due to carinal invasion, two patients (one with mucoepidermoid carcinoma and one with squamous-cell carcinoma) have survived for over 8 and 4 years, respectively, after complete resection. There were no long-term survivors among the patients with malignant pleural effusion. Pleuropneumonectomy did not improve survival. Extended lymph-node dissection for N3 disease was only commenced in recent years, so it is not yet clear whether it will affect the survival rate or not. However, 6 out of 19 patients who underwent extended lymph-node dissection including the contralateral lymph-node compartments are still alive, with 23 months being the longest survival. To date, there are 6 three-year survivors among our present series of stage IIIB patients who underwent operative treatment. From these results, it can be concluded that stage IIIB patients should not be uniformly excluded from consideration for surgery, but rather should be evaluated with regard to the possibility of performing complete resection.

Carcinoma, Non-Small-Cell Lung↗
PubMed1991

Improved survival in left non-small-cell N2 lung cancer after more extensive operative procedure.

The five-year survival rate of lung-cancer patients with left-sided N2 non-small-cell disease is worse than that for those with right-sided lesions and this is partly caused by inadequate nodal dissection due to anatomical limitations. To overcome the problem of performing nodal dissection in the left mediastinum, several modifications of the operative technique have been tried in the past 18 years. The survival rates of the patients treated by each procedure were retrospectively compared in this study. The dissection method for mediastinal nodes was modified at three periods (1973-1980, 1981-1985, and 1986-1990). The first period involved less extensive node dissection, in the second period more extensive dissection was enabled by mobilization of the aortic arch, and in the most recent systematic and extensive dissection was made possible by the use of a median sternotomy. The five-year survival rates of the left-sided N2 patients undergoing complete resection in the first and second period were 8.3%, and 15.4%, respectively. The three-year survival rate in the most recent period has risen to 30.8%. Complete and extensive dissection of the mediastinal nodes after performing a median sternotomy is the procedure of choice for lung-cancer patients with left-sided N2 disease.

Adult↗
PubMed1991

Antigen-presenting cells constitutively bind tumor antigens in the tumor-bearing state in vivo to construct an effective immunogenic unit.

Antigen-presenting cells (APC) constitutively process endogenous (self) proteins to bind the processed peptides to Ia molecules. In the present study, we investigated whether the same associative recognition also holds true for tumor-associated antigens (TAA) that are regarded as "self" molecules in tumor-bearing hosts. The following results were obtained: (i) an APC-depleted splenic T cell population from CSA1M tumor-immunized hosts was stimulated to produce interleukin 2 in vitro when co-cultured with APC from CSA1M-bearing mice, but not from normal mice; and (ii) a Thy-1+ cell-depleted APC population from CSA1M-bearing mice could produce CSA1M tumor-specific protection in vivo when inoculated into naive syngeneic mice. These results provide evidence for the functional binding in vivo of TAA to APC in the tumor-bearing state. The results are discussed in the context of the paradox that tumor-bearers fail to reject their own malignancy despite the formation on APC of an effective immunogenic unit which is capable of stimulating tumor-specific T cells.

Animals↗
PubMed1991

Effect of a new hyperosmotic agent, NIK-242 injection, on brain water content, metabolites and cerebral blood flow in cerebral ischemia in the spontaneously hypertensive rat.

We examined the effects of a new hyperosmotic agent (NIK-242inj.) on brain edema, energy metabolites and regional cerebral blood flow (r-CBF) during acute cerebral ischemia. Cerebral ischemia was induced by bilateral common carotid artery ligation (BLCL) using spontaneously hypertensive rats (SHR). The experimental animals were divided into 4 groups, A:20% NIK-242inj., B:20% mannitol, C:10% glycerol in 5% fructose, D:normal saline. All the animals were administered the agent or saline intravenously beginning at 1h after BLCL and continuing for 2h for a total dose of 6.8 ml/kg body weight. Brain water content and metabolites (ATP, lactate, pyruvate) were determined 3h after BLCL. Regional cerebral blood flow (r-CBF) in thalamus was also measured by the hydrogen clearance technique. The brain water content in the NIK-242inj. group was significantly lower than that of saline group. The concentration of brain ATP in the NIK-242inj. group remained higher than those of saline group. Accumulation of lactate in the NIK-242inj. group was less than in the mannitol and saline groups. The lactate/pyruvate ratio of the NIK-242 inj. group was significantly lower than that of the saline and mannitol groups. At 3h after BLCL, the reduction of r-CBF in the NIK-242inj. group was smaller than that of saline group. The present study suggests that NIK-242inj. as well as glycerol could ameliorate brain edema, disruption of brain energy metabolism and reduction of r-CBF in acutely induced cerebral ischemia.

Animals↗
PubMed1991

Mediastinal nodal involvement and the prognosis of non-small cell lung cancer.

We evaluated the effect of mediastinal lymph node metastasis on survival in 233 non-small cell lung cancer patients (N2 disease in 199 patients and N3 disease in 34 patients). Of the 199 patients with N2 disease, 144 underwent curative resection. The five-year survival rate of these 144 patients was 20.3 percent, which was significantly better than that of either the noncuratively resected N2 group or the N3 group. Nodal metastases in the curatively resected patients involved superior and inferior mediastinum irrespective of the location of the primary tumor. Patients with right-sided N2 lesions and metastases to the superior mediastinum had a worse survival than those with metastases to the inferior mediastinum. In contrast, patients with left-sided N2 lesions metastasizing to the inferior mediastinum had a significantly worse survival than those with lesions metastasizing to the superior mediastinum. Patients with single-level metastases had a significantly better survival rate than those with multilevel metastases. Subcarinal nodal involvement had an unfavorable effect in case of single-level metastasis, but did not affect the survival in cases of multilevel metastases. Our present study indicated that the survival of patients with N2 disease was affected by the operative radicality, by the number of levels of metastases, and also by the location of the nodal involvement. It seems appropriate that extensive mediastinal dissection should be performed irrespective of the location of the primary tumor.

Adenocarcinoma↗