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Biomedical subjects

M Yoshimura

Publications and source records attributed to M Yoshimura.

At least 37 records · Page 2Linked to original sources

Thyroid stimulating antibody in sera of Graves' ophthalmopathy patients as a possible marker for predicting the efficacy of methylprednisolone pulse therapy.

Nine patients with Graves' ophthalmopathy (GO) were treated with intravenous methylprednisolone pulse therapy and followed up by ophthalmological assessment, magnetic resonance imaging, and thyroid-associated autoantibody (thyroid stimulating antibody (TSAb), TSH binding inhibitor immunoglobulins (TBII), and anti-eye muscle antibody (EMAb)). Ophthalmological assessment was performed by the ophthalmopathy index (OI) which was made on the basis of the system recommended by the American Thyroid Association Committee. EMAb was expressed as the ratio of density of the 64 kDa band of eye muscle membrane to that of 92 kDa non-specific band found with all normal sera when assessed by western blotting. Five patients with mild ophthalmopathy (OI < 4) did not show progressive improvement in OI. Three of 4 patients with severe eye disease (OI > 4) showed a progressive and distinct improvement in OI. These 3 patients had high TSAb levels before methylprednisolone pulse therapy. One patient with severe ophthalmopathy did not respond to this pulse therapy; this patient's TSAb was negative. A significant positive correlation was observed between the activity of TSAb before treatment and the improvement in OI (delta OI) (r = 0.86, P < 0.01, n = 9). The relationship between delta OI and EMAb did not reach significance. These results suggest that TSAb in sera of GO patients can be a useful marker for predicting the efficacy of methylprednisolone pulse therapy.

Adolescent

[Renal arterial disease-induced tubulo-interstitial lesions].

Renal arterial disease-induced tubulo-interstitial lesions described in this chapter include benign arterio- and/or arteriolo-sclerotic and malignant nephrosclerosis, renal infarction and renal cortical necrosis. In these conditions renal glomeruli as well as tubules are always involved, and consequent loss of nephrons, or renal parenchyma results in interstitial fibrotic changes. The parenchymal lesions have a spectrum from slowly progressive atrophy and loss to necrosis of abrupt onset and disappearance of glomeruli and tubules. As for glomerular reactions to the ischemia, the intermediate type consisted of mesangial degeneration and epithelial cell proliferation described as "alterative glomerulitis" is noteworthy. Briefly, in renal arterial diseases, glomeruli are rather variably involved than tubules and loss of the parenchyma results in interstitial fibrosis.

Arteriosclerosis

Estimation of age from image processing of soft X-ray findings in Japanese male thyroid cartilages.

A method was developed for estimating the age at death based on image processing of soft X-ray pictures of thyroid cartilage from Japanese males. Data for 501 individuals were used to derive equations for this determination. Prior to image processing, gross morphological findings were used for estimation. Soft X-ray pictures indicated ossification with age and one index for image processing was introduced. The exponential function was applied to age estimation.

Adult

Estimation of age from soft X-ray findings of Japanese females thyroid cartilages.

A method for estimating the age at death using the image processing of soft X-ray pictures of the thyroid cartilages of Japanese females was examined. The soft X-ray pictures showed increasing ossification with age. One index for image processing was introduced. It is ossification rate (OSFR). Corresponding to this index, one age estimation equation was obtained. This age estimation equation showed accuracies of 60% or more for the age range of +/- 5 years and about 80% for the age range of +/- 8 years.

Adult

Autopsy cases of giant heart during the past ten years in Osaka (1985-1994).

We collected data from 30 autopsied cases, in which the heart weight were 800 g or more (maximum 1,300 g), at the Osaka Medical Examiner's office, for past 10 years. Among these cases, the cause of death was cardiac failure in 17 cases (56.7%), followed by pulmonary diseases (3 cases, 10.0%), cerebral infarction (3 cases, 10.0%), and aortic rupture (2 cases, 6.6%). The mean weight of the giant hearts was 880 g (about 77% of the cases) and 4 cases (13%) had 1,000 g or more. The mean height of the giant heart victims was close to the standard level, and thus the mean level of the ratio of heart weight to height were about 2.5 times higher than the standard levels. The liver weights were also greater by 500-1,000 g than the standard levels.

Adult

[Combination therapy of doxifluridine, pirarubicin and cisplatin for human gastric cancers implanted in nude mice].

In the preclinical study of a new combination therapy for gastric cancer, dFTP, consisting of doxifluridine (5'-DFUR), pirarubicin (THP) and cisplatin (DDP) as a modification of conventional FAP regimen (5-fluorouracil+Adriamycin+DDP), we compared antitumor and toxic effects of two sequential treatment schedules, single injection of DDP before or after 4 daily administrations of 5'-DFUR, on 5 strains of human gastric cancer bearing nude mice. Results indicated that both schedules of the dFTP regimen had potent antitumor effects. There was no significant difference between them. On the other hand, in terms of the host toxicity as observed by body weight loss, the post-DDP schedule was significantly less toxic than pre-DDP. These results suggest that dFTP regimen (post-DDP schedule) may be useful for clinical treatment of gastric cancers.

Adenocarcinoma

[Short somatosensory evoked potentials in patients with Fukuyama type congenital muscular dystrophy--a comparison with CT and MRI findings].

Seven patients with Fukuyama type congenital muscular dystrophy were studied. Low density areas (LDs) in the cerebral white matter on cranial CT were present in all 4 patients younger than 13 years of age and in 1 of 3 adult patients. LDs corresponded to low signals on T1 weighted MRI image and high signals on T2 weighted MRI image. The follow-up MRI showed a decreased tendency of the abnormal signals in 2 patients. Short somatosensory evoked potentials (SSEPs) in two infants, aged 4 months and 8 months, showed absent or depressed N1 amplitudes and delayed interpeak latencies from P3 to N1. N1 amplitudes increased on follow-up studies. SSEPs of five patients, who were older than 2 years of age, showed normal N1-P3 latencies. Amplitude of N1 was low in 2 patients with LD. Since the absent or depressed amplitude and delayed latency of N1 improved with the decrease of abnormal signals on MRI, we considered that N1 abnormalities show delayed myelination.

Adolescent

[Postoperative interstitial pneumonia in primary lung cancer patients--its causes and management].

Eight patients who developed interstitial pneumonia after surgery for primary lung cancer were reviewed to investigate its causes and the key points in treatment. These patients accounted for 1.8% of 633 operated lung cancer patients at our institution over the last 9 years. Risk factors such as bilateral recurrent laryngeal nerve palsy, preoperative chemoradiotherapy, and extensive mediastinal involvement were present in all of them. Pneumonia developed on the nonoperated side in all patients between the 2nd and 45th postoperative day (mean: 18 days). In most of the patients, faint reticular shadows initially appeared in the lower lobe of the nonoperated lung, rapidly spread to the upper lobe, and finally affected the whole lung. Among these eight patients, the initial five patients died because steroids were only administered after the pneumonia had become widespread, whereas the last three patients received early steroid therapy and were saved. The findings that 1) this pneumonia originated from the lower lobe of the nonoperated lung where blood flow is highest postoperatively, 2) the eosinophil count increased just before the onset of pneumonia, and 3) early steroid therapy and immunosuppressive therapy were effective suggest that an allergic or autoimmune mechanism may play some role in its development. When characteristic reticular shadows appear in the lower lobe on the nonoperated side in a lung cancer patient, even if not associated with any symptoms, an early diagnosis of interstitial pneumonia and initiation of steroid therapy is mandatory to ensure survival.

Aged

[Suppression of lung metastasis of B16 mouse melanoma cells by introduction of N-acetylglucosaminyltransferase III gene].

The beta 1-6 structure of N-oligosaccharides, formed by beta 1-6 N-acetylglucosaminyltransferase (GnT-V), is associated with metastatic potential. We established a highly metastatic subclone, B16-hm, from low metastatic B16-F1 murine melanoma cells. Introduction of the gene for beta 1-4 N-acetylglucosaminyltransferase (GnT-III) into B16-hm murine melanoma cells reduced the level of beta 1-6 structure by competing for the substrate, resulting in the suppression of lung metastasis in both syngeneic and nude mice, decreased invasiveness into the matrigel, and inhibition of cell attachment to collagen and laminin without affecting cell growth. The gene transfection altered the N-oligosaccharides of membrane glycoproteins, as measured by L-PHA and E-PHA binding. Our results demonstrated a causative role for beta 1-6 branches in the metastasis by gene transfection.

Animals

Assessment of urinary beta-core fragment of human chorionic gonadotropin as a new tumor marker of lung cancer.

BACKGROUND: Some patients with lung cancer have been found to have elevated levels of serum immunoreactive human chorionic gonadotropin (hCG)/hCG beta (IR-beta), but it is uncertain whether it would be valuable as a tumor marker. Recently, IR-beta has been demonstrated to consist of at least three different molecules, intact hCG, free hCG beta, and hCG beta-core fragment (beta-CF), in body fluids. In this study, the authors qualitatively analyzed IR-beta in the serum and urine of patients with lung cancer and assessed its clinical usefulness as a tumor marker. METHODS: Highly sensitive and specific enzyme immunoassays were established to measure intact hCG, free hCG beta, and beta-CF in the serum and urine of patients with lung cancer. RESULTS: Of 99 patients with lung cancer, almost half of the patients achieved positive values of IR-beta in the urine, although only 12 had elevated values of IR-beta in the serum. The greater part of the elevated urinary IR-beta was identified to be beta-CF by gel chromatography on Sephadex G-100 (Pharmacia LKB Biotechnology, Tokyo, Japan), leading the authors to assess its usefulness as a tumor marker for lung cancer. Based on the cutoff value (0.2 ng/mg of creatinine) from healthy subjects, the overall positive rate of urinary beta-CF for lung cancer was 48.5% (48 of 99 patients). The incidence of the marker increased with stage of disease, from 35.7% (15 of 42) in Stage I and 35.7% (5 of 14) in Stage II to 62.5% (20 of 32) in Stage III and 72.7% (8 of 11) in Stage IV. These positive rates exceeded or equaled those of the serum tumor markers, carcinoembryonic antigen, and squamous cell carcinoma (SCC)-related antigen, measured simultaneously in the same patients. The author were encouraged that there was no significant difference in the positive rates of urinary beta-CF between two major types of lung cancer: adenocarcinoma (49.2%) and SCC (45.2%). Immunohistochemical study revealed positive staining of IR-beta in the cancer tissues from 5 of 12 patients with elevated levels of IR-beta, in which most of the positive cases had the elevated levels of serum free hCG beta (> 0.5 ng/ml) and/or urinary beta-CF (> 1.0 ng/mg of creatinine). CONCLUSIONS: Ectopic production of IR-beta by lung cancer is not rare, and urinary beta-CF might be a potential tumor marker of lung cancer.

Adenocarcinoma

Effect of peptide nicking in the human chorionic gonadotropin beta-subunit on stimulation of recombinant human thyroid-stimulating hormone receptors.

It is now generally accepted that human chorionic gonadotropin (hCG) has thyroid-stimulating activity. Heterologous forms of the hCG molecule occur in the purified preparations extracted from urine of pregnant women and patients with trophoblastic diseases. This work was undertaken to determine the effect of peptide nicking in the hCG-beta subunit on its thyrotropic potency. Using Chinese hamster ovary cells expressing functional human thyroid-stimulating hormone (TSH) receptors, we examined the effect of nicked hCG on cycliC AMP (cAMP) production and receptor binding. The effect of human leukocyte elastase (hLE), a nicking enzyme, on standard hCG also was examined in the cAMP assay and on receptor binding. We studied five hCG preparations extracted from the urine of normal pregnancy (CR-127 and P8) and trophoblastic diseases (C2, C5 and M4). Two preparations (C2, 96% nicked and M4, 100% nicked in the beta 44-49 region) showed about a 1.5-fold potency of standard hCG CR-127, which is also 20% nicked in the same region. Non-nicked hCG (P8) had the weakest potency among all of the samples tested. Treatment of standard hCG with hLE increased the cAMP response about two-fold. Dose-dependent displacement of bovine [125I]TSH by standard hCG and hLE increased the cAMP response about two-fold. Dose-dependent displacement of bovine [125I]TSH by standard hCG and hLE-digested hCG was observed and was almost identical. We have confirmed the increased in vitro thyrotropic activity of hCG nicked in the beta-intercysteine loop on recombinant human TSH receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Digoxin-like immunoreactivity may contribute to hyperinsulinemia-associated hypertension in patients with glucose intolerance.

The role of endogenous digitalis-like factors in the pathogenesis of the hypertension associated with impaired glucose tolerance was investigated by measuring plasma digoxin-like immunoreactivity (DLI). Mean blood pressure correlated significantly with the obesity index, serum insulin-like immunoreactivity (IRI), and plasma DLI concentrations in subjects with impaired glucose tolerance (IGT). Plasma DLI concentrations also correlated significantly with the obesity index and serum IRI concentrations. Because increased insulin has been proposed to promote sodium reabsorption, sodium retention in turn has presumably caused an increase of natriuretic, digitalis-like factors reflected by the increased plasma DLI concentrations in patients with IGT. Consequently, increased DLI may contribute to the elevated arterial pressure in patients with hyperinsulinemia.

Adult

Activation of the thyrotropin (TSH) receptor by human chorionic gonadotropin and luteinizing hormone in Chinese hamster ovary cells expressing functional human TSH receptors.

It is well known that peptide heterogeneity exists in the hCG-beta subunit in pregnancy and in patients with trophoblastic diseases. To elucidate the differences in thyrotropic activity of hCG molecules, we examined cAMP accumulation and TSH receptor binding of intact hCG, hLH, and a recombinant hCG that lacked the C-terminal extension on the beta-subunit, hCG (alpha wt/beta delta T), using Chinese hamster ovary (CHO) cells transfected with hTSH receptors. hLH, which shares 85% sequence identity with the hCG-beta molecule except for the C-terminal amino acid residue extension of the hCG-beta subunit, bound to the TSH receptor and stimulated adenylate cyclase about 10 times more potently than hCG on a molar basis. This was consistent with the result that cAMP stimulation by mutant hCG (alpha wt/beta delta T) was greater than intact hCG. hLH also increased iodide uptake and thymidine incorporation in FRTL-5 rat thyroid cells more potently than intact hCG. These results demonstrate that hLH is a more potent TSH than hCG and that the C-terminal extension of the hCG beta-subunit can interfere with hCG interaction with the hTSH receptor. hCG lacking the C-terminal extension of the beta-subunit occurs in the mixture of heterogeneous hCG molecular forms of pregnancy and trophoblastic diseases and may contribute to the hyperthyroidism in patients with hydatidiform mole, choriocarcinoma, and hyperemesis gravidarum.

Analysis of Variance

Excitatory amino acid receptors involved in primary afferent-evoked polysynaptic EPSPs of substantia gelatinosa neurons in the adult rat spinal cord slice.

Intracellular recordings were made from substantia gelatinosa (SG) neurons in spinal cord slices to determine a subclass of excitatory amino acid receptors involved in polysynaptic excitatory postsynaptic potentials (EPSPs). In the majority of neurons, polysynaptic EPSPs evoked by A delta fiber were not affected by 2-amino-5-phosphonovaleric acid (APV), while all EPSPs including monosynaptic EPSPs were depressed by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). All spontaneous EPSPs were blocked by CNQX, while spontaneous EPSPs in a few SG neurons were attenuated by APV. These observations suggest that polysynaptic EPSPs evoked through A delta fibers are predominantly mediated by activation of the non-N-methyl-D-aspartate (non-NMDA) receptor subclass.

2-Amino-5-phosphonovalerate

Cloning and expression of a Ca(2+)-inhibitable adenylyl cyclase from NCB-20 cells.

A cDNA that encodes an adenylyl cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] has been cloned from NCB-20 cells, in which adenylyl cyclase activity is inhibited by Ca2+ at physiological concentrations. The cDNA clone (5.8 kilobases) was isolated by polymerase chain reaction (PCR) using degenerate primers designed by comparison of three adenylyl cyclase sequences (types I, II, and III) and subsequent library screening. Northern analysis revealed expression of mRNA (6.1 kilobases) corresponding to this cDNA in cardiac tissue, which is a prominent source of Ca(2+)-inhibitable adenylyl cyclase. The clone encodes a protein of 1165 amino acids, whose hydrophilicity profile was very similar to those of other mammalian adenylyl cyclases that have recently been cloned. A noticeable difference between this protein and other adenylyl cyclases was a lengthy aminoterminal region before the first transmembrane span. Transient expression of this cDNA in the human embryonic kidney cell line 293 revealed a 3-fold increase in cAMP production in response to forskolin compared with control transfected cells. In purified plasma membranes from transfected cells, increased adenylyl cyclase activity was also detected, which was susceptible to inhibition by submicromolar Ca2+. Thus, this adenylyl cyclase seems to represent the Ca(2+)-inhibitable form that is encountered in NCB-20 cells, cardiac tissue, and elsewhere. Its identification should permit a determination of the structural features that determine the mode of regulation of adenylyl cyclase by Ca2+.

Adenylyl Cyclase Inhibitors

Histological study on ouabain immunoreactivities in the mammalian hypothalamus.

The endogenous digitalis-like factor (EDLF) which has recently been purified from human plasma and identified as 'ouabain', a cis-trans-cis steroid of plant origin, is thought to be similar to the hypothetical humoral factor, 'endogenous digitalis-like substance (EDLS)'. In order to examine the hypothesis that EDLS is produced in the hypothalamus, we prepared an ouabain-specific antibody, and applied it to rat and macaque brains. Ouabain immunoreactivities were observed in the hypothalamus of both species. The immunopositive neurons were distributed in paraventricular and supraoptic nuclei, and some other hypothalamic regions. Their nerve fibers were seen abundantly in the hypothalamo-neurohypophysial regions. These results strongly support the possibility of existence of cis-trans-cis steroid including EDLF in mammalian brain.

Animals