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Biomedical subjects

H Nakabayashi

Publications and source records attributed to H Nakabayashi.

At least 55 records · Page 3Linked to original sources

A silencer element for the lipoprotein lipase gene promoter and cognate double- and single-stranded DNA-binding proteins.

Transfection experiments with constructs containing various 5'-deleted fragments of the human lipoprotein lipase (LPL) promoter and the chloramphenicol acetyltransferase reporter gene revealed an LPL silencer element (LSE) in the region of nucleotides -225 to -81 of the LPL gene that functioned in Chinese hamster ovary (CHO) and HeLa cells. Gel retardation competition analysis showed the presence of a nuclear factor(s) capable of binding to the sequence of nucleotides -169 to -152 of LSE (LSE-6) in a single-stranded (opposite-strand) and double-stranded specific fashion, the binding affinity being almost the same in the two binding forms. Site-directed mutagenesis indicated that almost the entire sequence of LSE-6 was necessary to form the complexes and also critical for silencing activity in CHO cells. The amounts of this binding factor(s) in CHO and HeLa cells were closely associated with transcriptional silencing activity. Photochemical cross-linking experiments indicated that the single- and double-stranded elements recognized the same binding factor(s) with molecular masses of 54 to 63 kDa and 109 to 124 kDa. The 109- to 124-kDa DNA binding factor(s) was found to be a doublet of that of the 54- to 63-kDa factor by isoelectric focusing or by increasing the time of exposure to UV irradiation. When inserted upstream of another gene such as that of the simian virus 40 enhancer/promoter of pSV2CAT, the sequence of nucleotides -190 to -143 (LSE-1) also suppressed transcription of the reporter gene in CHO cells. These results strongly suggest that the LSE plays a role in regulation of LPL gene expression by suppressing its transcription.

Animals↗

[A case of multilocular thymic cyst with myasthenia gravis].

We reported a case of 53-year-old male who was admitted to our hospital for ptosis and difficulty in chewing. Because of positive for Tensilon test and high dose anti-acetylcoline receptor antibody, we established diagnosis for myasthenia gravis. Additionally he was pointed out a cystic lesion at anterior superior mediastinum on CT and MRI. As a result we diagnosed him as thymic cyst with myastenia gravis. The extended thymectomy was performed. Histological examination revealed that the mass was a multilocular thymic cyst which is reported by Suster, who suggested that the multilocular thymic cyst arises from processes of reactions to an acquired inflammatory change. There was no report for cases of multilocular thymic cyst with myastenia gravis. MTC-like changes are sometimes presented in association with thymic Hodgkin's disease or thymic seminoma. Malignant transformation of thymic cyst were also reported. So careful examination and evaluation for cystic lesion within thymus are required.

Humans↗

[Clinical significance of measurement of a novel basement membrane-associated collagen levels in serum].

We measured serum levels of a basement membrane-associated collagen(BMC) by enzyme linked immunosorbent assay using two recently produced monoclonal antibodies (named JK-199 and JK-135) to evaluate that's clinical significance. JK-199 reacted with alpha 1 (IV) chain in triple helical region of type IV collagen and JK-132 is considered to react with an unidentified alpha (IV) related collagen chain. BMC was determined in sera of patients with chronic liver diseases (n = 27), healthy volunteers (n = 30) and in random serum samples of in- or outpatients of our hospital (n = 1125). The degree of fibrosis of the chronic liver diseases was estimated by computed image analysis for the biopsy specimens. BMC levels in sera of healthy volunteers as 0-40ng/ml. Serum BMC levels were significantly higher than that in healthy volunteers in chronic active hepatitis 2A (56.9 +/- 27.9ng/ml; mean +/- SD), 2B (80.9 +/- 39.1ng/ml) and liver cirrhosis (114.5 +/- 26.6ng/ml). Serum BMC levels showed positive correlation with fibrosis area/total area(%) in biopsy specimens of chronic liver diseases (r = 0.678; p < 0.001). Total 149 samples (from 127 patients) of 1125 random serum samples (13.2%) showed increased BMC and 70 of 127 patients with abnormal high BMC (55.1%) had liver diseases. These results suggest that serum BMC increases mainly in patients with liver diseases, especially with progression of chronic liver diseases.

Adult↗

[A case of pulmonary tumorlet with tuberculoma misdiagnosed as small cell lung carcinoma by transbronchial lung biopsy].

A 59-year-old woman was picked up by chest X-ray findings. Her CT scan film showed a tumor shadow in the upper lobe of the left lung, and by transbronchial lung biopsy, she was diagnosed as a small cell lung carcinoma. Lobectomy was performed, but the lesion was diagnosed as tuberculoma by frozen section. Furthermore, on postoperative histological examination, a minute lesion of tumorlet, which was histologically identical to that preoperatively detected by transbronchial lung biopsy was found in the adjacent tissues of the tuberculoma. Pulmonary tumorlet is clinically a rare lesion, but the diagnosis and treatment for small-sized tumor or tumor-like lesion may be carefully done, taking into account the existence or co-existence of tumorlet lesion.

Biopsy↗

Sequence of the 5'-flanking region of the gene encoding human muscle glycogen synthase.

The 5'-flanking region of the gene encoding human muscle glycogen synthase was isolated from a human placental genomic library and sequenced. The sequence is TATA-less and G+C-rich, and putative transcription-controlling sequences were identified. Furthermore, a simple (dC-dA)n sequence repeat was identified about 4 kb upstream from the start codon. This sequence was highly polymorphic and five alleles were typed in the Japanese population using the polymerase chain reaction.

Animals↗

A unique receptor-mediated mechanism in vagal chemoreception of somatostatin in the hepatoportal area.

Our previous results have indicated that the hepatic vagus is receptive to intraportal appearance of somatostatin-14 (SS), a gastroenteropancreatic peptide hormone, in rat. To examine the actual involvement of the SS receptor mechanism in the neural reception, the receptor function was modified with monoclonal antibody against rat neural SS receptor. Our monoclonal antibody of IgG1(kappa) isotype bound to the SS binding site of the receptor in competition with the ligand. Intraportal SS injection at a physiological dose (3.05 pmol) significantly facilitated the afferent firing discharge rate of the hepatic vagus in rats anesthetized with urethane and chloralose. The antibody ascites, but not the control ascites, administered intraportally 5 min prior to the SS injection abolished completely the SS-induced increase in discharge rate. However, when the antibody was administered more than 15 min after the SS injection, the SS-induced increase in discharge rate did appear, implying an unique post-receptor mechanism in reception. The present results indicate that the SS receptor mechanism operates in the neurochemoreception of SS, suggesting the existence of a hepatic vagal, receptor-mediated system for monitoring the hormone secreted from the splanchnic organs.

Afferent Pathways↗

Marked improvement of diabetic diarrhea with the somatostatin analogue octreotide.

Somatostatin and its long-acting analogue octreotide have been used in various diarrheal disorders, including neoplastic and nonneoplastic diseases of the gastrointestinal tract. In two insulin-dependent diabetic patients with autonomic neuropathy and chronic steatorrheic diarrhea refractory to conventional medications, subcutaneous administration of octreotide markedly improved the volume and frequency of stools in both patients. This change was accompanied by a clear improvement in their rapid gastrointestinal tract transit times. The treatment also greatly improved their orthostatic hypotension. No adverse effects of octreotide were observed after treatment for 7 months in one patient and 2 months in the other.

Adult↗

Choroid plexus metastasis from gastric cancer--case report.

A 64-year-old male presented with a unique choroid plexus metastasis from gastric cancer. Computed tomography and magnetic resonance imaging demonstrated a moderately enhanced mass in the lateral ventricle. The tumor was totally removed and histological examination revealed adenocarcinoma. Systemic investigation revealed gastric cancer. The differential diagnosis for intraventricular masses should include the possibility of metastasis from unidentified primary lesions.

Adenocarcinoma↗

[DNA polymorphism in the human glycogen synthase gene and non-insulin dependent diabetes mellitus in Japanese].

Using PCR-RFLP analysis, no A2 allele which is related with the frequency of NIDDM in Finland was detected in Japanese patients with NIDDMs and controls. We found out a new microsatellite of CA repeat in the human muscle glycogen synthase (MGS) gene, and the polymorphism of the repeat number detected by the PCR. The allele frequency was not significantly different between NIDDMs and controls. However, the allele frequency in the patients without high total cholesterolemia was significantly different from that of controls, and 19 repeat allele was significantly higher in this group than that in controls. These suggest that the MGS gene or neighboring genes are related with one of the disease genes of diabetes mellitus without high total cholesterolemia.

Asian People↗

[The effect of alacepril on insulin sensitivity in patients with essential hypertension].

The aim of this study was to determine the effect of angiotensin-converting-enzyme inhibitor, alacepril, on insulin sensitivity in patients with essential hypertension (EHT). Ten patients (5 men and 5 women) with EHT (3 with mild diabetes and 2 with borderline glucose tolerance) participated. We measured insulin sensitivity using the two-hour euglycemic-hyperinsulinemic clamp technique and plasma glucose and insulin responses to a 75 g oral glucose tolerance test (75 g OGTT) before and after 6-8 weeks of treatment with alacepril (dose, 50 mg/day). Glucose infusion rate (GIR) during the last 30 min of the clamp study increased from 5.83 +/- 0.70 to 6.59 +/- 0.65 mg per kilogram of body weight per minute (P < 0.05) after treatment with alacepril. The insulin-sensitivity index, which was calculated by dividing the GIR by the mean insulin concentration during the same period of the clamp, also increased from 5.91 +/- 0.66 to 7.20 +/- 0.90 (P < 0.05) after treatment with alacepril. Plasma glucose responses to a 75 g OGTT were changed from diabetic pattern to borderline pattern in two patients and from borderline pattern to normal pattern in one patient after treatment with alacepril. Body weight did not significantly change throughout the study in any of the patients studied. Our study demonstrated that alacepril significantly improves insulin sensitivity in patients with EHT.

Adult↗

HNF-4 increases activity of the rat Apo A1 gene.

Apolipoprotein A1 (Apo A1) is the major protein component of high density lipoprotein (HDL) particles. HDL particles mediate the removal of cholesterol from extra-hepatic tissues via a process known as reverse cholesterol transport. Augmented production of Apo A1 will likely be beneficial to those who suffer from the consequences of hypercholesterolemia. One approach to increase expression of the protein is to identify nuclear factor(s) that enhance Apo A1 promoter activity. Therefore, we have used transient transfection to study a limited portion (-474 to -7) of the gene and showed that a cis-regulatory element, site C had a permissive effect on the ability of an adjacent site B to increase promoter activity by 30-fold. The importance of element C prompted us to identify the factor(s) that interact with this site. Results showed that HNF-4, a new member of the thyroid/steroid hormone receptor superfamily interacts with site C to enhance activity of the promoter. Based on this observation and that of the known inhibitory effects of ARP-1 on site C, we postulate a model which may account for the tissue-specific expression of the rat Apo A1 gene.

Animals↗

Assessment of autonomic nervous activity by heart rate spectral analysis in patients with variant angina.

The purpose of this study was to assess the role of the autonomic nervous system in the pathogenesis of coronary artery spasm in patients with variant angina. We evaluated cardiac sympathetic and parasympathetic activity from the power (logarithmic scale) of the low-frequency (approximately 0.04 to 0.12 Hz) and the high-frequency (approximately 0.22 to 0.32 Hz) spectral components of heart rate variability with Holter monitoring in seven patients with nocturnal variant angina and in 11 healthy men who served as control subjects. None of the patients had organic coronary artery stenosis as determined by angiography. Low-frequency and high-frequency logarithmic values were calculated for each 5-minute period from 30 minutes before to immediately before each angina attack. The logarithmic low-frequency value during the 5-to-0-minute period was greater than the low-frequency values during most of the other periods (p < 0.05 - p < 0.01). The logarithmic high-frequency values during the 10-to-5-minute and 5-to-0-minute periods were greater than those during the 30-to-25-minute period (p < 0.05 and p < 0.01, respectively). These data indicate that parasympathetic activity increased during the 10 minutes before attacks of nocturnal variant angina, whereas sympathetic activity with vagal modulation increased during the 5 minutes before such attacks. The same pattern of changes in heart rate variability was found in the absence of ST-segment elevation in patients and in control subjects. So this phenomenon was not just associated with coronary spasm and variant angina. It is suggested that circadian variation in disease activity is also associated with spontaneous attacks.

Adult↗

A rapid molecular diagnosis of posttransfusion graft-versus-host disease by polymerase chain reaction.

A woman with recurrent Paget's disease of the vulva developed acute graft-versus-host disease (GVHD) 12 days after radical surgery and massive blood transfusion. Molecular diagnosis of lymphocyte chimerism in the peripheral blood was made by polymerase chain reaction (PCR) directed against a Y chromosome-specific sex-determining region Y (SRY) gene. PCR with skin biopsy after onset of GVHD also revealed infiltration of SRY-positive donor lymphocytes. The diagnosis was confirmed by HLA-DNA typing with PCR-sequence-specific oligonucleotide that revealed the presence of complex HLA-DR chimerism in the peripheral lymphocytes collected after onset of GVHD. The use of SRY-directed PCR is a rapid technique for the early diagnosis of acute posttransfusion GVHD in female patients.

Base Sequence↗

Electrophysiologic evaluation of intermittent sacral nerve dysfunction in lumbar spinal canal stenosis.

Intermittent sacral nerve dysfunction, induced by walking in lumbar spinal canal stenosis, may cause symptoms including hyperesthesia and pain in perineum, urinary bladder incontinence, and penile erection. However, it is difficult to objectively document these symptoms. Evoked external urethral sphincter potentials by conus medullaris stimulation were measured both before walking and after walking in five patients who complained of sexual organ or urinary dysfunction during walking, and were compared with simultaneously induced sacral nerve symptoms. These potentials were also measured during surgery. Sacral nerve symptoms were reproduced by walking 80-350 meters (average 177.5 m). These potentials disappeared in one patient and were decreased in four patients at the time when the claudicant symptoms disabled the patient during walking. The amplitude subsequently recovered in keeping with relief of those symptoms during rest. Monitoring of these potentials during surgery showed an increase of amplitude shortly after the decompression procedure of the cauda equina. In conclusion, this measuring method was valuable as an objective evaluation of intermittent sacral nerve dysfunction in lumbar spinal canal stenosis.

Aged↗

[A case report of Weber's syndrome associated with supranuclear vertical gaze palsy caused by the ipsilateral thalamomesencephalic lesion].

We report a rare case showing Weber's syndrome associated with supranuclear vertical gaze palsy caused by the ipsilateral lesion of the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), which is regarded as the supranuclear control center of vertical gaze. To date, no literature concerning Weber's syndrome associated with the ipsilateral riMLF lesion was documented. The patient was a 53-year-old female, who suddenly developed unconsciousness and left-sided weakness. Neurological findings on admission revealed right third nerve palsy, severe supranuclear vertical gaze palsy, almost complete convergence palsy, left hemiparesis and hyperreflexia with positive Babinski's sign on the left side. There was no sign of pupillary disturbance or no abnormality of the horizontal movements of the left eye. The vestibulo-ocular reflex of the left eye was preserved. There was no sensory disturbance. Cranial MRI had the advantages in demonstrating unilateral ischemic lesions at the cerebral peduncle and the thalamomesencephalic junction involving the unilateral riMLF on the right side. Recent reports have demonstrated that supranuclear vertical gaze palsy is caused by the unilateral riMLF lesion. We confirm that the unilateral riMLF lesion causes supranuclear vertical gaze palsy in our case and that cranial MRI has the advantages in demonstrating the specific lesion.

Eye Movements↗

Identification and characterization of two enhancers of the human albumin gene.

A 12.5-kilobase pair (kb) segment upstream of the human albumin gene was analyzed for transcription enhancing activity using transient transfection analysis, gel mobility shift assays, DNase I footprinting, and site-specific mutagenesis. Two enhancer regions were identified, one 1.7 kb upstream of the transcription initiation site (E1.7) and the other 6 kb upstream (E6). In E1.7, a nuclear protein from HuH-7 hepatoma cells binds to an AT-rich sequence, GTTACTAATTGAC. Competition gel mobility shift assays suggested that this protein is HNF-1, which regulates the promoter of the albumin gene and several other liver-specific genes. A 60-base pair E1.7 fragment carrying the AT-rich sequence stimulates a heterologous (alpha-fetoprotein) promoter in a dose-dependent manner. In E6, a HuH-7 nuclear protein binds to a GT-rich sequence, TGTTTGGC.A 27-base pair E6 fragment carrying this sequence is able to stimulate the SV40 promoter in an orientation-independent manner. An alteration of this sequence by site-specific mutagenesis resulted in the loss of transcriptional activity as well as binding to the HuH-7 nuclear protein. Competition gel mobility shift assays showed that homologous elements exist in the albumin promoter. These results show that the promoter and enhancer of the human albumin gene are regulated by two common transcription factors through two shared cis-acting elements, one AT-rich and the other GT-rich.

Albumins↗