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Biomedical subjects

S Hashimoto

Publications and source records attributed to S Hashimoto.

At least 955 records · Page 53Linked to original sources
PubMed1989

Mechanism of a lymphocyte abnormality associated with HLA-B8/DR3 in clinically healthy individuals.

An important unanswered question in clinical immunology is why the histocompatibility antigens HLA-B8/DR3 should be associated with at least nine quite different immune-mediated diseases. The purpose of this study was to examine the mechanism of an immunologic abnormality, commonly found in healthy individuals with HLA-DR3, that may reflect an immune defect predisposing to autoimmunity. Fourteen healthy subjects with HLA-DR3 had a proliferative response to a suboptimal concentration of PHA nearly eight-fold lower than that observed in 10 individuals without this HLA antigen. Impaired responsiveness to PHA was more strongly associated with HLA-DR3 than with HLA-B8. The IL-2 concentration in mitogen-stimulated cultures was similarly decreased in subjects with HLA-DR3 and was highly predictive of the proliferative response 24 h later (r = 0.82, P less than 0.0001). Inhibition of IL-2 utilization by anti-IL-2 receptor antibody indicated that the reduced IL-2 concentration reflects impaired lymphokine production rather than increased utilization. Expression of IL-2 receptors is decreased in these subjects, although the magnitude of their proliferative response is appropriate for the available lymphokine. These results indicate that impaired lymphocyte activation associated with HLA-DR3 reflects impaired IL-2 production and an abnormality of activation events preceding the production of this lymphokine.

Adult↗
PubMed1989

[Determination of CSF guanase activity in multiple sclerosis: a comparative study on various parameters to monitor the disease activity].

Forty two patients with multiple sclerosis (MS) were subjected to determination of CSF guanase activity, CSF IgG concentration, Tibbling's IgG index and Kurtzke's expanded disability status scale (EDSS) together with multimodal evoked potentials (MEPs), which consisted of somatosensory evoked potentials to arm and leg stimulation, visual evoked potential and auditory brainstem response. All patients were divided into active (n = 28) and inactive (n = 14) group, where an "active" was defined as a case revealing a relapse within one month prior to the study. The results were as follows: 1. CSF guanase activity was significantly high in active MS as compared with inactive MS (p less than 0.001), and the same trend was found in CSF IgG concentration (p less than 0.01), but not in IgG index. 2. Abnormal MEP was closely associated with elevated CSF guanase activity in active MS (p less than 0.05), but not in inactive MS. 3. In regard to the disease activity, EDSS was significantly high in active MS as compared with inactive MS (p less than 0.01), and EDSS was also significantly high in abnormal MEP group (p less than 0.001). 4. EDSS was closely correlated with CSF guanase activity in active MS (p less than 0.005), but not in inactive MS. 5. Judging from serial determinations of the parameters in 6 patients, CSF guanase activity, less susceptive to steroid hormone therapy than CSF immunoglobulin level, was found parallel to EDSS, however, both CSF IgG concentration and IgG index failed to correlated with EDSS. In summary, CSF guanase activity was thought to be a sensitive parameter in multiple sclerosis, reflecting not only the disease activity but also spatial involvement in the CNS.

Adult↗
PubMed1989

[Exercise-induced precordial ST depression in patients with prior inferior myocardial infarction with single vessel disease].

We investigated the mechanisms of exercise-induced precordial ST depression in prior inferior myocardial infarction in single vessel disease, and attempted to differentiate ST depression in single vessel from multivessel disease. Subjects were categorized as; Group I (n = 18), with inferior myocardial infarction and single vessel disease without (n = 11; Ia) and with (n = 7; Ib) exercise-induced precordial ST depression and group II (n = 10), inferior myocardial infarction with multivessel disease. The subjects were examined using 12-lead exercise ECG, stress T1-201 myocardial imaging and stress radionuclide ventriculography. Compared to group Ia, exercise-induced precordial ST depression in group Ib was associated with extensive infarction extending into the inferoseptal left ventricular wall by T1-201 myocardial imaging. Worsening of septal wall motion was also more frequently observed on stress radionuclide ventriculography. For detecting multivessel disease in prior inferior myocardial infarction, exercise ECG and radionuclide ventriculography had poor specificity and predictive value compared to stress T1-201 myocardial imaging. We conclude that exercise-induced precordial ST depression observed in patients with prior inferior myocardial infarction due to single vessel disease reflects a peri-infarction ischemia in the inferoseptal wall of the left ventricle. Great caution is necessary when predicting multivessel disease in prior inferior myocardial infarction using exercise ECG. Stress T1-201 myocardial imaging is the most accurate diagnostic means for this purpose.

Aged↗
PubMed1988

Characterization of cyclic GMP-binding sites of cyclic GMP-dependent protein kinase by rapid filtration assay.

The kinetics of cyclic [3H]GMP binding to the purified cyclic GMP-dependent protein kinase (cG kinase) were studied by using the rapid filtration assay method with polyethyleneimine-treated glass filters (method A), and the data were compared with those of the (NH4)2SO4 precipitation procedure (method B), which has been used for many previous studies on cyclic GMP binding to cG kinase. Each method gave a similar stoichiometry of approx. 2 mol of cyclic GMP/mol of cG kinase subunit; however, other binding kinetics obtained with these two methods were different. The dissociation of bound cyclic [3H]GMP from the kinase showed a single slow component when method A was used, whereas rapid and slow dissociation components were observed with method B. The Scatchard plot of cyclic [3H]GMP binding with method A was linear with a Kd value of 11 +/- 2 nM, suggesting that the two intrachain binding sites have similar high affinity for cyclic GMP. Results obtained on cyclic nucleotide analogue specificity of the two intrachain cyclic GMP-binding sites were also different between these two methods. These findings suggest that cG kinase has two high-affinity cyclic GMP-binding sites per subunit in the native state, and that when (NH4)2SO4 is added, ostensibly to stop the binding reaction, one low-affinity site is created from one high-affinity site.

Animals↗
PubMed1988

Activation of the adenovirus-2 E2a late promoter during inhibition of protein synthesis by cycloheximide.

The 5' termini of human adenovirus 2 (Ad2) E2a mRNA, which starts at two separate (early and late) promoter regions, were mapped on Ad2 nucleotide sequences with the aid of primer extension analysis and quantitated. In the early stage (6 h) of Ad2 infection of KB cells and 293 cells, E2a mRNA started mostly at the early (75.4 mp) promoter region. When these infected cells were cultured in the presence of cycloheximide from 1 to 6 h postinfection, the transcription from the late (72.2 mp) promoter region increased. Especially in 293 cells, approx. 50% of E2a mRNA started at the late promoter region. We conclude from the results that the activation of the late promoter during infection does not depend on viral DNA replication. Our results suggest the involvement of cellular protein(s) in this activation.

Adenoviruses, Human↗
PubMed1988

[Effects of o,p'-DDD on pituitary-gonadal function in patients with Cushing's disease].

O,p'-DDD has a cytotoxic action and inhibits the cholesterol side chain cleavage enzyme, 11 beta-hydroxylase, 3 beta-hydroxysteroid dehydrogenase coupled with delta 5 to 4 isomerase and 21-hydroxylase of the adrenal cells. However, the effects of o,p'-DDD on gonadal steroidogenesis are still unknown. In the present study, the effects of o,p'-DDD on Plasma cortisol, pregnenolone, 17 alpha-hydroxypregnenolone (17-OH-pregnenolone), progesterone, 17 alpha-hydroxyprogesterone (17-OH-progesterone), 11-deoxycorticosterone (DOC), corticosterone, dehydroepiandrosterone (DHEA), delta 4-androstenedione (androstenedione), estradiol, and LH and FSH were investigated in 3 patients with Cushing's disease before and after the administration of o,p'-DDD. The results are presented here. In Case 1 (18 yr old female) who had had secondary amenorrhea for 2 years, the plasma levels of cortisol, pregnenolone, 17-OH-pregnenolone, DHEA, androstenedione, testosterone, estradiol and corticosterone were elevated. The basal levels of plasma LH and FSH and the responses of both gonadotropins were lower than those of women with eumenorrhea. The plasma levels of progesterone, DHEA and testosterone decreased to normal 2 months after the beginning of the administration of o,p'-DDD. She restored menstrual cycles ranging from 40 to 50 days 3 months after the administration of o,p'-DDD, but with anovulatory bleeding. She showed a biphasic body temperature pattern with plasma progesterone and estradiol levels indicating corpus luteum formation 11 months after the start of the treatment, when plasma cortisol as well as progesterone and androgen were reduced to normal. The basal levels of FSH and LH and responses of these gonadotropins were slightly improved at that time. The plasma levels of cortisol, DHEA and androstenedione were high in Case 2 (38 yr old male) and Case 3 (45 yr old male), whereas plasma testosterone level was normal in Case 2 and low in Case 3. The plasma levels of these 3 steroids were normalized 28 days after the beginning of the o,p'-DDD administration. These results suggest that o,p'-DDD does not interfere with gonadal steroidogenesis in Cushing's disease.

Adolescent↗
PubMed1988

Adult T-cell leukemia with leukemia cell infiltration into the gastrointestinal tract.

Five cases of untreated adult T-cell leukemia (ATL) with leukemia cell infiltration into the gastrointestinal (GI) tract were reported. X-ray findings of the GI tract showed diffuse abnormal mucosal patterns throughout the GI tract in all five patients. Endoscopic findings corresponded well with the x-ray findings. Pathologic examination of biopsied specimens from all five patients revealed diffuse and extensive leukemic infiltration into the stomach and/or the large intestine.

Adult↗
PubMed1988

Monoclonal antibody to rat brain actin antigenically enhanced with HVJ (Sendai virus) M protein.

Monoclonal antibody to rat brain actin was easily produced using HVJ (Sendai Virus) M protein to enhance the antigenicity of the actin. This monoclonal antibody was determined to be IgM with a kappa light chain. By immunoblot analysis the antibody was also shown to react with rat brain actin but not with HVJ M protein on nitrocellulose sheets. Utilizing the antibody, neuronal cytoplasm in the cerebral cortex, the anterior and posterior horns in the spinal cord, the spinal ganglion and astrocytes showed positive immunohistochemical staining by light microscopy. However, Purkinje cells showed variable staining, some staining intensely, while others were negative. All of neurons in specific anatomical locations showed always positive staining but variable intensities. Vascular walls were stained only faintly. By electron microscopy, neuronal cytoplasm showed diffuse positive staining. Other areas showed a positive reaction, including dendrites, the postsynaptic densities, and a few capillary endothelial cells and arterial smooth muscle cells. The results suggest that the HVJ M protein was effective for producing monoclonal antibody to brain actin, and that the antibody could be utilized for the immunohistochemical study of neuronal elements in both normal and pathological conditions.

Actins↗
PubMed1988

Ultrastructural study of chromatolytic neurons in an adult-onset sporadic case of amyotrophic lateral sclerosis.

Ultrastructural features of chromatolytic neurons observed in a sporadic case with amyotrophic lateral sclerosis (ALS) are reported. A 70-year-old woman died of weakness and atrophy of the four limbs, bulbar and facial muscles, and hyperreflexia, of 3 1/2 years' duration. Neuronal loss was marked in the anterior horn of the spinal cord, with degeneration of the pyramidal tracts. Most of the remaining neurons showed chromatolysis. Some of the chromatolytic neurons contained faintly eosinophilic inclusions with a halo. Few spheroids were observed. Hypoglossal nuclei, nucleus ambiguus, motor nuclei of N.VII and N.V were well populated, but contained several chromatolytic neurons. Ultrastructurally, the chromatolytic neurons contained aggregates of fibrils thicker than the 10-nm neurofilaments. These fibrils were arranged randomly, and were closely associated with granular materials as well as rough endoplasmic reticulum. Neurofilamentous accumulations reported to be common in sporadic ALS were rare in this case. No Bunina body was observed.

Actin Cytoskeleton↗
PubMed1988

Intraarterial digital subtraction angiography with carbon dioxide: superior detectability of arteriovenous shunting.

Intraarterial digital subtraction angiography (IADSA) with carbon dioxide (CO2) was performed on 41 patients with liver or renal diseases. CO2 produced no hypersensitivity reactions, and the pain or feeling of warmth was relatively mild compared with iodinated contrast media. Although the image quality of the arterial or capillary phase was inferior to that with iodinated contrast media, the detectability of arteriovenous shunting was excellent. IADSA with CO2 may become an effective method for detecting arteriovenous shunting which cannot be demonstrated with conventional angiography or DSA with iodinated contrast medium.

Adult↗
PubMed1988

Radioimmunodetection of human pancreatic tumor xenografts using DU-PAN II monoclonal antibody.

The potential of DU-PAN II, monoclonal antibody (IgM), which was raised against the human tumor cell line, was evaluated for radioimmunodetection of human pancreatic tumors (PAN-5-JCK and EXP-58) grown in nude mice. 125I-labeled DU-PAN II was accumulated into PAN-5-JCK producing DU-PAN II antigen with a tumor-to-blood ratio of 2.72 +/- 3.00, but it did not localize in EXP-58 because of insufficient DU-PAN II. There was no significant uptake of 125I-nonimmunized IgM in PAN-5-JCK. These facts indicated the specific tumor uptake of DU-PAN II. Excellent images of the tumor PAN-5-JCK were obtained 3 days after the injection of 125I-DU-PAN II. Gel chromatography was also investigated with respect to the plasma taken from mice injected with antibody, or incubated with antibody in vitro. The results indicate that circulating antigen affected the tumor uptake of DU-PAN II: The more the tumor grew, the higher the amount of antigen excreted into the blood, leading to the degradation of DU-PAN II before it reached the tumor sites. Consequently, the immunoscintigram of the small tumor was remarkably clear. The catabolism and the radiolysis of the labeled IgM injected are critical points in applying immunoscintigraphy.

Animals↗