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Biomedical subjects

R Yamamoto

Publications and source records attributed to R Yamamoto.

At least 109 records · Page 6Linked to original sources

Disopyramide decreases the fasting serum glucose level in man.

The effect of disopyramide, a class Ia antiarrhythmic drug, on the serum glucose level was evaluated in 6 consecutive in-patients. A 19-hour starvation test was repeated with oral administration of sustained-release disopyramide (150 mg) 0 and 12 hours after starting the test. Serum glucose levels during the starvation test decreased with disopyramide administration from a mean value of 96.5 +/- 1.8 to 85.9 +/- 1.4 mg/dl (24 samples, p < 0.05). The average reduction of the serum glucose level by disopyramide in each patient was 9.7 +/- 2.2 mg/dl. The decrease in the serum glucose level was not related to the serum concentration of disopyramide or serum creatinine levels. The decrease in the serum glucose level was larger in older patients (r = 0.75) and in light patients under 45 kg. These results suggested that disopyramide reduced the fasting serum glucose levels even in normal ranges as a common side effect of the drug, and that not only the occurrence of severe hypoglycemia but also the decrease in glucose levels were influenced by multiple factors including age and body weight.

Age Factors↗

Poorer nutritional status of the older-generation in a Japanese farming village, as related to fewer types of food consumed.

This study was carried out to determine whether the most recent nutritional improvements in Japanese farming villages were due to improvement in the diet of the young only or across all ages. Food duplicates for 24 h were collected. The number of food items and the adequacy of each nutrient level were compared between subgroups, by age of cooking and those eating meals. The older-generation used and ate fewer food items resulting in poorer nutrition. The most recent improvement in nutrition in the farming villages of Japan was found mainly to affect the younger-generation with the older-generations being more poorly nourished.

Adult↗

Detection of WT1 mRNA in urine from patients with kidney diseases.

Detachment of glomerular epithelial cells (GEC) from glomerular basement membrane (GBM) could account for a part of the pathogenic mechanism of proteinuria seen in primary and secondary renal diseases. The Wilms' tumour suppresser gene (WT1) is strictly expressed in GEC in the adult kidney. Mutations of WT1 gene have been implicated in progressive renal damage. Utilizing nested RT-PCR we detected mRNA of WT1 in the urine of patients with renal diseases. Seven of 20 (35%) chronic glomerulonephritis (CGN), eight of 20 (40%) diabetes mellitus (DM) with proteinuria, and two of 24 (8.3%) rheumatic diseases were WT1 positive. Interestingly, only one of 51 (2%) DM without proteinuria was WT1 positive. None of the healthy volunteers or cystitis patients were WT1 positive. This is the first report describing the detection of endogenous WT1 mRNA, an important gene in progressive renal failure, from patients' urine. This technique could be a powerful tool in the search for information about glomerular damage in clinical settings as well as for WT1 mutations or isoform imbalance at the research level without renal biopsy.

Adult↗

Cyclic AMP-dependent synthesis and release of adrenomedullin and proadrenomedullin N-terminal 20 peptide in cultured bovine adrenal chromaffin cells.

Adrenomedullin and proadrenomedullin N-terminal 20 peptide are peptides with multiple physiological functions and are most abundant in adrenal medulla. We studied whether the cAMP-dependent pathway is involved in the regulation of synthesis and release of adrenomedullin and proadrenomedullin N-terminal 20 peptide in cultured bovine adrenal chromaffin cells. Exposure of the cells to dibutyryl cAMP (dbcAMP) increased a progressive accumulation of immunoreactive-adrenomedullin and immunoreactive-proadrenomedullin N-terminal 20 peptide in the extracellular medium, while reciprocally decreasing their cellular content in a time-dependent manner. The decrease of levels of both peptides in the cells was much greater in extent than the increase of the peptides in the medium. H89, an inhibitor of cAMP-dependent protein kinase attenuated these changes, induced by dbcAMP. The resulting changes by dbcAMP and H89 were similar to those of chromogranin B, a marker peptide of chromaffin granule. Northern blot analysis showed that the mRNA encoding these peptides, detected as a band of 1.6 kb, was decreased by the treatment with dbcAMP. The effect of dbcAMP on mRNA was attenuated by H89, and was reversible as the decreased mRNA level caused by dbcAMP could be returned to control levels by culturing cells after removal of dbcAMP. These results suggest that the cAMP-dependent protein kinase pathway stimulates the release of adrenomedullin and proadrenomedullin N-terminal 20 peptide, whereas it lowers synthesis of these peptides via the reduction of their transcript level.

Adrenal Medulla↗

Protein kinase C and the opposite regulation of sodium channel alpha- and beta1-subunit mRNA levels in adrenal chromaffin cells.

Our previous [3H]saxitoxin binding and 22Na influx assays showed that treatment of cultured bovine adrenal chromaffin cells with 12-O-tetradecanoylphorbol 13-acetate (TPA) or phorbol 12,13-dibutyrate (PDBu), an activator of protein kinase C (PKC), decreased the number of cell surface Na channels (IC50 = 19 nM) but did not alter their pharmacological properties; Na channel down-regulation developed within 3 h, reached the peak decrease of 53% at 15 h, and was mediated by transcriptional/translational events. In the present study, treatment with 100 nM TPA lowered the Na channel alpha-subunit mRNA level by 34 and 52% at 3 and 6 h, followed by restoration to the pretreatment level at 24 h, whereas 100 nM TPA elevated the Na channel beta1-subunit mRNA level by 13-61% between 12 and 48 h. Reduction of alpha-subunit mRNA level by TPA was concentration-dependent (IC50 = 18 nM) and was mimicked by PDBu but not by the biologically inactive 4alpha-TPA; it was prevented by H-7, an inhibitor of PKC, but not by HA-1004, a less active analogue of H7, or by H-89, an inhibitor of cyclic AMP-dependent protein kinase. Treatment with cycloheximide, an inhibitor of protein synthesis, per se sustainingly increased the alpha-subunit mRNA level and decreased the beta1-subunit mRNA level for 24 h; also, the TPA-induced decrease of alpha-subunit mRNA and increase of beta1-subunit mRNA were both totally prevented for 24 h by concurrent treatment with cycloheximide. Nuclear run-on assay showed that TPA treatment did not alter the transcriptional rate of the alpha-subunit gene. A stability study using actinomycin D, an inhibitor of RNA synthesis, revealed that TPA treatment shortened the t(1/2) of alpha-subunit mRNA from 18.8 to 3.7 h. These results suggest that Na channel alpha- and beta-subunit mRNA levels are differentially down- and up-regulated via PKC; the process may be mediated via an induction of as yet unidentified short-lived protein(s), which may culminate in the destabilization of alpha-subunit mRNA without altering alpha-subunit gene transcription.

Adrenal Medulla↗

Development of primary hypothyroidism with the appearance of blocking-type antibody to thyrotropin receptor in Graves' disease in late pregnancy.

Spontaneous remission of Graves' disease with a decrease of thyroid stimulating antibody (TSAb) activity is commonly observed in pregnancy. In this article, however, a Graves' patient who developed primary hypothyroidism with an appearance of thyroid stimulation-blocking antibody (TSBAb) activity in late pregnancy is reported. A 25-year-old woman presented with clinical and biochemical hyperthyroidism with an elevation of 99mTcO4- thyroid uptake (4.7%; normal range, 0.7%-3.0%) and mildly elevated activity of thyrotropin-binding inhibitory immunoglobulin (TBII; 30.4%). She was euthyroid with normal TBII (8.0%) and TSAb (126%) before pregnancy, when the patient was taking a 5-mg daily dose of methimazole (MMI). MMI was stopped by the patient when she became pregnant. Subsequently, the patient progressed into primary hypothyroidism with a marked elevation of TBII activity (78.4%) in the third trimester of the pregnancy (at that time, TSAb activity was not detected). TSBAb measured 2 weeks later was detected at the activity of 85.0%. Replacement therapy was initiated with levothyroxine (LT4) (0.05-0.1 mg/day), which was discontinued on the 55th day postpartum because of the onset of mild thyrotoxicosis followed by short-term euthyroid state despite high TSBAb activity. Subsequently, because the patient developed primary hypothyroidism 5 months after delivery, replacement therapy with LT4 (0.1-0.125 mg/day) was readministered. Thus, it is suggested that the development of hypothyroidism with the appearance of TSBAb in Graves' patients can occur even in late pregnancy.

Adult↗

Malignant Brenner tumors of the ovary and tumor markers: case reports.

We investigated the tumor marker for malignant Brenner tumors, which had not been established because of the rarity and variable histological criteria. Representative areas of two cases of malignant Brenner tumor were investigated by means of the peroxidase-antiperoxidase method using monoclonal antibody to CA125 and CA72-4 antigen and the streptavidin-biotin immunoperoxidase complex method using monoclonal antibody to SCC antigen. Based on clinical course and immunohistochemical studies, serum CA125 and CA72-4 for Case 1 and SCC and CA72-4 for Case 2 were appropriate tumor markers for the establishment of the extent of tumor burden before treatment and to monitor the response to therapy. The discrepancy of the tumor markers of the two present cases is considered to be a reflection of the difference in the malignant component of these cases. However, serum CA72-4 was an appropriate tumor marker for both malignant Brenner tumors.

Aged↗

Structural study of an RNA aptamer for a Tat protein complexed with ligands.

An RNA aptamer for an HIV Tat protein has been isolated by the in vitro SELEX method. The RNA aptamer binds to the Tat protein 50-100 times more strongly than native TAR RNA does. Here, we have investigated the structure of the RNA aptamer complexed with ligands, partial peptide fragments of the Tat protein or argininamide, by multidimensional 1H/13C/15N NMR. It is strongly suggested that two U:A:U base triples are formed in the RNA aptamer upon binding of ligands. Specific hydrogen bonds between arginine side chains of ligands and guanine bases located adjacent to the base triples are identified. On the basis of many intramolecular and intermolecular NOEs, a structural model of the complex has been constructed.

Base Sequence↗

Hypoxia inhibits baroreflex vagal bradycardia via a central action in anaesthetized rats.

It is known that arterial baroreflexes are suppressed in stressful conditions. The present study was designed to determine whether and how hypoxia affects arterial baroreflexes, especially the heart rate component, baroreflex vagal bradycardia. In chloralose-urethane-anaesthetized rats, baroreflex vagal bradycardia was evoked by electrical stimulation of the aortic depressor nerve, and the effect of 15 s inhalation of hypoxic gas (4% O2) was studied. Inhalation of hypoxic gas was found to inhibit baroreflex vagal bradycardia. The inhibition persisted after bilateral transection of the carotid sinus nerve. Cervical vagus nerves were cut bilaterally and their peripheral cut ends were stimulated to provoke vagal bradycardia of peripheral origin so as to determine whether hypoxia could inhibit vagal bradycardia by acting on a peripheral site. In contrast to baroreflex vagal bradycardia, the vagus-induced bradycardia was not affected by hypoxic gas inhalation. It is concluded that baroreflex vagal bradycardia is inhibited by hypoxia and the inhibition is largely mediated by its direct central action.

Animals↗

Fetal treatment of congenital heart block ascribed to anti-SSA antibody: case reports with observation of cardiohemodynamics and review of the literature.

PROBLEM: Maternal anti-SSA(B) antibody crosses the placenta and causes fetal myocarditis, congenital heart block (CHB), hydrops fetalis, and intrauterine fetal death. The aim of this study was to evaluate corticosteroids' efficacy as a treatment for CHB. METHOD OF STUDY: One fetus with complete CHB and one fetus with incomplete CHB due to anti-SSA(B) antibody received maternal prednisolone (PSL) and dexamethasone (DEXA) treatments. Heart rate, cardiothoracic ratio (CTR), left ventricular fractional shortening (FS), and preload index (PLI) were longitudinally measured by serial fetal echocardiograms. RESULTS: In the former case, after maternal PSL/DEXA administration, improvement of cardiohemodynamics, i.e., the reduction of PLI from 1.7 to 0.4, CTR from 70 to 52%, and FS from 63 to 54% were observed. In the latter case, second degree 2:1 block was converted to 3:2 block/sinus rhythm, resulting in the increase of the fetal heart rate from 65 to 116 beats per minute (bpm). CONCLUSIONS: We disclosed for the first time the beneficial effects of corticosteroids in the fetal cardiohemodynamics and conduction system of affected fetuses with the presence of maternal anti-SSA(B) antibodies.

Adult↗

Characterization of novel antimicrobial peptoids.

Peptoids differ from peptides in that peptoids are composed of N-substituted rather than alpha-carbon-substituted glycine units. In this paper we report the in vitro and in vivo antibacterial activities of several antibacterial peptoids discovered by screening combinatorial chemistry libraries for bacterial growth inhibition. In vitro, the peptoid CHIR29498 and some of its analogues were active in the range of 3 to 12 microg/ml against a panel of gram-positive and gram-negative bacteria which included isolates which were resistant to known antibiotics. Peptoid antimicrobial activity against Staphylococcus aureus was rapid, bactericidal, and independent of protein synthesis. beta-Galactosidase and propidium iodide leakage assays indicated that the membrane is the most likely target of activity. Positional isomers of an active peptoid were also active, consistent with a mode of action, such as membrane disruption, that does not require a specific fit between the molecule and its target. In vivo, CHIR29498 protected S. aureus-infected mice in a simple infection model.

Animals↗

Complementary randomly amplified polymorphic DNA (RAPD) analysis patterns and primer sets to differentiate Mycoplasma gallisepticum strains.

Randomly amplified polymorphic DNA (RAPD) analysis was used to differentiate 7 strains of Mycoplasma gallisepticum. Six commercially available primers or primer combinations were screened for their ability to differentiate vaccine and type strains. Although major and minor bands were produced with each primer, many of the primers were unsuitable for strain differentiation. The use of primer 6 and combined primers 3 and 4 resulted in complementary RAPD banding patterns for each M. gallisepticum strain. Eleven different isolates representing 7 different strains were segregated into 7 different patterns, corresponding to the 7 strains.

Amino Acid Sequence↗

Abundance of low molecular weight phosphotyrosine protein phosphatase in the nerve-ending fraction in the brain.

The distribution of low molecular weight phosphotyrosine protein phosphatase (LMW-PTP) in subcellular fractions of rat brain tissue was investigated by immunoblotting analysis using anti-LMW-PTP antibody. The enzyme was detected in the 105000 g precipitate in addition to the supernatant of brain homogenate, even after the precipitate was extensively washed, and was abundant in the particulate fraction of nerve endings. Nerve ending LMW-PTP was effectively solubilized by 1% Triton X-100 or 1% deoxycholate, though the enzyme was solubilized by thorough sonication. Two forms of LMW-PTP, designated as LMW-PTP-I and -II, were separated from the nerve ending-rich fraction by chromatofocusing. Nerve endings PTP-I and -II were different in molecular weight, isoelectric point and susceptibility to activators and inhibitors. The properties of nerve endings LMW-PTP-I and -II were similar to those of cytosolic LMW-PTP-I and -II. The abundance of LMW-PTP in nerve endings as well as in the cytosol suggests that this enzyme plays an important role in synaptic function.

Animals↗

Favorable life-style modification and attenuation of cardiovascular risk factors.

In order to develop an effective counseling system for prevention of cardiovascular diseases, the association of a favorably changed life-style with improved risk factors was examined. Participants were 7,321 office workers aged 30-69 years from in and around Nagoya city. The age-adjusted odds ratio (OR) and its 95% confidence interval (CI) were calculated to assess the likelihood of risk factor improvement by favorable life-style modifications during a 3-year period. Those who began to eat breakfast and increased their vegetable intake normalized their previously abnormal diastolic blood pressure with more than twice the likelihood (adjusted OR [95% CI] 2.89 [1.29-6.46] and 2.60 [1.18-5.75], respectively). 'Began to eat breakfast' was also significantly associated with normalized total cholesterol (TC) (1.84, [1.05-3.21]). 'Stopped eating till full' significantly normalized the body mass index (2.03; [1.25-3.28]), uric acid (1.65; [1.07-2.52]) and TC (1.43; [1.04-1.97]). Those who started regular exercise significantly normalized their high-density lipoprotein-cholesterol (HDL-C) abnormality with 1.69-times the likelihood (1.69; [1.24-2.29]) and those who began to walk briskly also improved their TC abnormality (1.85; [1.19-2.89]). HDL-C was normalized with 2.55-times the likelihood in those who quit smoking (2.55; [1.68-3.86]). Because favorable life-style modifications can attenuate abnormal cardiovascular risk factors, then proper advice on specific risk factors should be routinely given at each health check-up in order to prevent the onset of cardiovascular diseases in subsequent years.

Adult↗

Heterogeneous expression of P450 2C12 mRNA in female rat liver.

The heterogeneous expression of P450 2C12 mRNA was studied in the rat liver. Liver was sampled from female rat, approximately 40 mg portions being removed from 18 different locations. Total RNA was isolated and subjected to northern blot analysis. The membrane was hybridized with a (32)P-labeled rat P450 2C12 gene-specific oligonucleotide probe. After the hybridized P450 2C12 gene-specific probe had been washed out, the membrane was hybridized again with a rat oligonucleotide probe for the detection of actin mRNA expression. In comparison with actin mRNA expression, P450 2C12 mRNA was not evenly expressed throughout the 18 different locations in the liver. The present results show the heterogeneous expression of P450 2C12 mRNA in the rat liver.

Animals↗

[Period of time patients with advanced non-small cell lung cancer could remain at home during CIC--therapy (cisplatin + ifosfamide + CPT-11)].

Two phase I studies (CIC-therapy) were conducted in advanced non-small cell lung cancer (NSCLC) to determine the maximum tolerable dose (MTD) of CPT-11 combined with cisplatin and ifosfamide, and MTD of cisplatin combined with CPT-11 and ifosfamide with G-CSF support, respectively. Both regimens were repeated every 4 weeks. G-CSF was administered on days 5 to 18. Eighty-eight patients were registered in both studies. The overall response rate was 59.1%, and the median survival time was 393 days. In all patients enrolled, we examined retrospectively the period of time they could remain at home during chemotherapy. We examined this period divided into day 1-18 and day 18-28 until the third course. Although myelotoxicity occurring during the third course was the most severe, the mean time was 7.1 days (day 1-18 2.2, day 18-28 4.9) for the first course, 10.1 days (day 1-18 4.0, day 18-28 6.0) for the second course, and 11.0 days (day 1-18 4.7, day 18-28 6.3) for the third course. Only two patients came to the hospital because of acute upper respiratory tract infection. Although CIC-therapy was an aggressive chemotherapy with G-CSF support, most of the patients were able to stay at home during chemotherapy.

Adult↗

A surgical case of atypical aortic coarctation using cardiopulmonary bypass.

We report a 44-year-old woman with atypical aortic coarctation accompanied by cerebral artery disease. She was hospitalized for vertigo. An extra-anatomic bypass between the ascending aorta and abdominal aorta was performed using partial cardiopulmonary bypass under moderate hypothermia to reduce the after load of the left ventricle and maintain cerebral blood flow and cerebral perfusion pressure. The postoperative course was uneventful and there was no postoperative neurological deficiency.

Adult↗

Paralemmin, a prenyl-palmitoyl-anchored phosphoprotein abundant in neurons and implicated in plasma membrane dynamics and cell process formation.

We report the identification and initial characterization of paralemmin, a putative new morphoregulatory protein associated with the plasma membrane. Paralemmin is highly expressed in the brain but also less abundantly in many other tissues and cell types. cDNAs from chicken, human, and mouse predict acidic proteins of 42 kD that display a pattern of sequence cassettes with high inter-species conservation separated by poorly conserved linker sequences. Prenylation and palmitoylation of a COOH-terminal cluster of three cysteine residues confers hydrophobicity and membrane association to paralemmin. Paralemmin is also phosphorylated, and its mRNA is differentially spliced in a tissue-specific and developmentally regulated manner. Differential splicing, lipidation, and phosphorylation contribute to electrophoretic heterogeneity that results in an array of multiple bands on Western blots, most notably in brain. Paralemmin is associated with the cytoplasmic face of the plasma membranes of postsynaptic specializations, axonal and dendritic processes and perikarya, and also appears to be associated with an intracellular vesicle pool. It does not line the neuronal plasmalemma continuously but in clusters and patches. Its molecular and morphological properties are reminiscent of GAP-43, CAP-23, and MARCKS, proteins implicated in plasma membrane dynamics. Overexpression in several cell lines shows that paralemmin concentrates at sites of plasma membrane activity such as filopodia and microspikes, and induces cell expansion and process formation. The lipidation motif is essential for this morphogenic activity. We propose a function for paralemmin in the control of cell shape, e.g., through an involvement in membrane flow or in membrane-cytoskeleton interaction.

Amino Acid Sequence↗