Intrahepatic arterioportal fistula most likely due to liver biopsy: an unusual cause of esophageal variceal hemorrhage.
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Biomedical subjects
Publications and source records attributed to S Sugano.
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We studied the influence of training on autonomic nervous function in the horse. For this purpose, Holter electrocardiogram (ECG) was recorded before and after training from 24 Thoroughbred horses (2-year-olds) and autonomic nervous function was evaluated by the power spectral analysis of heart rate (HR) variability. We obtained HR, low-frequency (LF) power, high-frequency (HF) power, and LF/HF ratio from recording. We set LF at 0.01-0.07 Hz and HF at 0.07-0.6 Hz. The HF power is thought to reflect primarily parasympathetic nervous function. Both the sympathetic and parasympathetic nervous systems have been shown to contribute to the LF power. The LF/HF ratio is considered as an index of the cardiac sympathovagal balance. Second degree atrioventricular blocks were found in the ECG of 3 and 5 horses before and after the training period, respectively. Ventricular premature depolarisations were detected in a horse after the training period. Heart rate decreased at night. The lowest HR values had a tendency to appear in the early morning. Both the LF and HF power tended to be higher at night. However, the LF/HF ratio was almost the same throughout the day. The HR was significantly decreased by training. Although the LF power and LF/HF ratio were significantly increased, the HF power was not changed by training. These results suggest that parasympathetic nervous activity may be fully activated even before training in this species.
Tail blood flow (TBF) in the rat markedly increases during sympathetic withdrawal such as hyperthermia or lumbar sympathetic blockade. However, a long-term alteration of TBF after chronic sympathetic denervation is not well understood. In the present study, TBF following lumbar sympathectomy (LSX) was observed to ascertain whether subsequent changes in TBF occur in the absence of the sympathetic nervous activity in the rat tail. Assessed by recording tail and rectal temperature, the LSX immediately caused an increase in TBF. TBF was gradually decreased along with time and returned to the sham operated (SO) control level within 4 days. About a week after the surgery, a rapid increase in TBF in response to whole body heating was almost abolished in denervated animals. Neither hexamethonium (20 mg/kg, i.v.) for ganglion blockade nor intra-arterial infusion of alpha-receptor antagonist, phentolamine (10, 100 microg) produced vasodilation in LSX animals. Nitroprusside, a donor of nitric oxide, produced an increase in TBF in both LSX and SO animals. These results indicate that the tail vasculature after LSX constricts with capability to be vasodilated independent of sympathetic reinnervation. Quantification of the tail vascular mRNA expression by reverse transcriptase-polymerase chain reaction showed less endothelial nitric oxide synthetase in LSX group than that in SO group whereas endothelin-1 was not significantly different in both groups. It is suggested that functional changes in tail vascular endothelium takes at least a part in the reduction in TBF after LSX.
We isolated and determined the sequence of cDNA encoding mouse BH-protocadherin (BH-Pcdh) from heart. It encodes a 1069 amino acids (aa) polypeptide exhibiting an overall 97% identity with human BH-Pcdh-a and 83% identity with Xenopus NF-protocadherin. We also determined the alternatively spliced cytoplasmic tail sequence. The cytoplasmic tail of mouse BH-Pcdh-b is short (2 aa) compared with that of human BH-Pcdh-b (14 aa). The cytoplasmic tail of mouse BH-Pcdh-c showed 100% aa identity with that of human BH-Pcdh-c except for a 8-amino-acid insertion. Northern blot analysis revealed two major transcripts were expressed in brain and heart. Mouse BH-Pcdh-a mRNA was detected as a single band of approximately 5.5-kb. The mRNA level of mouse BH-Pcdh-a and -c were persistently detected by RT-PCR in developmental process of brain and heart, but that of mouse BH-Pcdh-b was elevated only in fetus and neonatal stage of brain. The chromosomal location of the mouse BH-Pcdh gene was determined as 5C3-D using fluorescence in situ hybridization.
BACKGROUND AND PURPOSES: The purpose of the study was to document diurnal variation of autonomic nervous functions by use of power spectral analysis of heart rate (HR) variability. METHODS: To clarify characteristics of power spectral analysis of HR variability, electrocardiogram (ECG), blood pressure (BP), and respiratory (Resp) waveform simultaneously were recorded. RESULTS: Two major spectral components were examined at low (LF)- and high (HF)-frequency bands for HR variability. Coherence between HR and Resp variabilities and HR and BP variabilities was maximal at approximately 0.14 and 0.03 Hz, respectively. On the basis of these data, two frequency bands of interest--LF (0.01 to 0.07 Hz) and HF (0.07 to 1.0 Hz)--were defined. Autonomic blockade studies indicated that the parasympathetic system mediated the HF and LF components, whereas the sympathetic system mediated only the LF component; HR had a diurnal pattern. The LF and HF bands in the dark phase tended to be higher than those in the light phase. The LF-to-HF ratio had a diurnal pattern similar to that of the HR. CONCLUSION: Parasympathetic nervous activity in miniature swine may be predominant in the dark phase. The characteristics of power spectra and diurnal variations of autonomic nervous functions are almost the same as those of humans. Therefore, miniature swine may be a useful animal model for future biobehavioral and pharmacotoxicologic studies.
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We studied the diurnal variations of autonomic nervous function in rats. For this purpose, a long-term electrocardiogram (ECG) was recorded from conscious and unrestrained rats using a telemetry system, and the autonomic nervous function was investigated by the power spectral analysis of heart rate variability. No arrhythmias were observed in the ECG of any of the rats. Nocturnal patterns, in which the values of heart rate in the dark phase (2000-0600) were higher than those in the light phase (0600-2000), were observed. All normal rats shared a characteristic pattern in their power spectrum analysis. Both low-frequency and high-frequency power in the light phase were higher than those in the dark phase. However, these differences were not statistically significant (P > .05). The low frequency to high frequency ratio also showed a nocturnal pattern. The value in the dark phase was significantly higher (P < .05) than that in the light phase. These results suggest that the sympathetic nervous activity is predominant in the dark phase in rats. Therefore, we believe that this information may be useful for future biobehavioral studies.
The circadian clock-associated 1 (CCA1) gene encodes a Myb-related transcription factor that has been shown to be involved in the phytochrome regulation of Lhcb1*3 gene expression and in the function of the circadian oscillator in Arabidopsis thaliana. By using a yeast interaction screen to identify proteins that interact with CCA1, we have isolated a cDNA clone encoding a regulatory (beta) subunit of the protein kinase CK2 and have designated it as CKB3. CKB3 is the only reported example of a third beta-subunit of CK2 found in any organism. CKB3 interacts specifically with CCA1 both in a yeast two-hybrid system and in an in vitro interaction assay. Other subunits of CK2 also show an interaction with CCA1 in vitro. CK2 beta-subunits stimulate binding of CCA1 to the CCA1 binding site on the Lhcb1*3 gene promoter, and recombinant CK2 is able to phosphorylate CCA1 in vitro. Furthermore, Arabidopsis plant extracts contain a CK2-like activity that affects the formation of a DNA-protein complex containing CCA1. These results suggest that CK2 can modulate CCA1 activity both by direct interaction and by phosphorylation of the CCA1 protein and that CK2 may play a role in the function of CCA1 in vivo.
The p53 protein, which regulates the rate of cell division and death, is the most frequently mutated tumor suppressor to be identified so far in human cancers. Recently, a gene with significant homology to p53, termed p73, has been identified in a chromosomal region that is implicated in the molecular pathogenesis of neuroblastoma. We have cloned a second human p53-related gene, termed p73L, which shows strong amino-acid similarity to p73. The p73L gene is mapped to human chromosome 3q27-28 using in situ hybridization technique. p73L encodes a protein of 586 amino acids and its putative DNA binding domain (DBD) has high identities to those of p53 (60.6%) and to p73 (87.8%). Northern blot analysis, which demonstrated that the expression profiles of p73L and p73 mRNAs are distinct in some tissues, implies that p73 and p73L may have separate, distinct roles in different tissues.
We have developed a method that enables us to isolate cDNAs of putative membrane proteins. The system is designed to isolate a cDNA which can provide the transmembrane domain to the extracellular part of the IL-2 receptor alpha chain. We constructed a p18Mac vector by putting part of the IL-2 receptor alpha chain cDNA that encoded its signal sequence and extracellular domain, a cDNA cloning site and a poly(A) additional signal after a strong promoter SRalpha. If a cloned cDNA provides a transmembrane domain in-frame, the extracellular domain of the IL-2 receptor alpha chain will be expressed on the surface of the transfected cells. Otherwise, the chimeric protein will be either secreted or retained inside the transfected cells. We made a cDNA library using p18Mac and screened for cDNA clones which allowed the expression of the extracellular domain of the IL-2 receptor alpha chain on the cell surface. Of the 2000 clones screened, 5 clones were scored as positive. Partial sequence analysis revealed that one clone encoded the amyloid precursor protein, two others encoded mitochondrial proteins and the rest were new. These results suggest the system is effective in isolating cDNAs encoding putative membrane proteins.
We have identified a novel member of the cadherin superfamily. Among the members of the superfamily, this protein exhibited the highest overall homology with protocadherin-1 (46-49% identity). Its mRNA was predominantly expressed in the brain and heart. Hence, we named the gene BH-protocadherin (BH-Pcdh) (HGMW-approved symbol PCDH7). BH-Pcdh has an extracellular domain consisting of seven repeats of the cadherin motif (EC 1 to 7). EC2 of BH-Pcdh is unique in having a 55-amino-acid insertion in the middle of the motif. There are three isoforms of BH-Pcdh, denoted -a, -b, and -c, which have different cytoplasmic tails and a 47-amino-acid deletion in the EC2-3 region of BH-Pcdh-c. While only a 9.0-kb message was detected in normal tissues, 4.5- and 9.0-kb mRNA species were seen in the human lung carcinoma cell line A549. Furthermore, only the 4.5-kb mRNA was detected in HeLa cell S3 and human gastric cancer cell lines MKN28 and KATO-III. Southern blot analysis indicated that the BH-Pcdh gene is likely to be conserved among various vertebrates. The BH-Pcdh gene was localized to human chromosome 4p15. Interestingly, 4p15 is a region of loss of heterozygosity in some head and neck squamous cell carcinomas.
The regulator of G-protein signaling (RGS) proteins have recently been identified as signal transduction molecules which have structural homology to SST2 of Saccharomyces cerevisiae and EGL-10 of Caenorhabditis elegans. Multiple genes homologous to SST2 are present in higher eukaryotes, and the group of these genes is termed the RGS family. RGS proteins are involved in the regulation of heterotrimeric G-proteins by acting as GTPase-activators. A putative new member of the RGS family was isolated from a neuroblastoma cDNA library. The amino acid sequence deduced from the cDNA possessed all consensus motifs of the RGS domain and showed closest homology to mouse RGS5 (90% identical), indicating that it was human RGS5 (hRGS5). The messenger RNA of hRGS5 was abundantly expressed in heart, lung, skeletal muscle, and small intestine, and at low levels in brain, placenta, liver, colon, and leukocytes. The chromosome localization of the gene in the 1q23 region was determined by a monochromosomal hybrid panel and a radiation hybrid panel.
Huntington disease (HD) is an inherited neurodegenerative disorder which is associated with CAG expansion in the coding region of the gene for huntingtin protein. Recently, a huntingtin interacting protein, HIP1, was isolated by the yeast two-hybrid system. Here we report the isolation of a cDNA clone for HIP1R (huntingtin interacting protein-1 related), which encodes a predicted protein product sharing a striking homology with HIP1. RT-PCR analysis showed that the messenger RNA was ubiquitously expressed in various human tissues. Based on PCR-assisted analysis of a radiation hybrid panel and fluorescence in situ hybridization, HIP1R was localized to the q24 region of chromosome 12.
We identified a novel gene encoding a RING finger (C3HC4-type zinc finger) protein from a human neuroblastoma full-length enriched cDNA library. This cDNA clone consists of 1919 nucleotides with an open reading frame of a 485-amino acid protein. From reverse transcription (RT)-polymerase chain reaction (PCR) analysis, the messenger RNA was ubiquitously expressed in various human adult tissues. The chromosomal location of the gene was determined on the chromosome 6p21.3 region by PCR-based analyses with both a human/rodent monochromosomal hybrid cell panel and a radiation hybrid mapping panel.
Electrolyte abnormalities have become an increasingly important cause of arrhythmias owing to the widespread use of high-potency diuretics. Hypokalemia is one of the common complications of diuretic use. Although some studies of hypokalemia induced by furosemide as well as of potassium-deficient diets in the rat have been reported, the electrocardiographic (ECG) changes during hypokalemia in the rat are poorly understood. This study was designed to examine such changes. For this purpose, hypokalemia was induced by furosemide administration, and the diagnostic criteria for ECG manifestations of hypokalemia were determined. During hypokalemia, conduction in most parts of the heart was suppressed to an extent depending on plasma potassium concentration. Prolongation of the QT interval was also observed, which agrees with findings in humans and dogs. Furthermore, prolonged durations of the P wave and QRS complex were observed during hypokalemia in the rat. The extent of alteration of the PR interval induced by hypokalemia was less significant than that of P wave and QRS complex durations. These results suggest that the excitabilities of the myocardium in the atria and ventricles may be affected by extracellular potassium level rather than by the atrioventricular conduction system in the rat. Wave amplitude, except that of the P wave, was decreased by severe hypokalemia. These changes were not dependent on the plasma potassium concentration. Typical T wave changes observed with hypokalemia in humans and dogs did not occur in the rat. The ECG manifestations of acute hypokalemia in the rat did not include the typical T wave changes seen in species with ST-segment type ECGs; however, other ECG parameter changes occurring with hypokalemia were qualitatively similar to those in other species. These results may be useful for testing the toxicity of potassium-depleting drugs in the rat.
The response to histamine of nasal afferents has been studied in guinea pigs by recording the electrical activity of the whole ethmoidal nerve (EN) or that of single units. Guinea pigs were anaesthetized with urethane and breathed through a tracheostomy. Prior to intranasal instillation of histamine (1 x 10(-4)-10(-1) M), the nasal mucosa was treated with 20 microl of saline (0.9% NaCl) or HCl (pH = 2), and in some cases, H2SO4 (pH = 2). In other experiments, following HCl instillation animals were pretreated by tripelennamine (1 x 10(-2) M) and/or cimetidine (1 x 10(-2) M) in order to determine the histamine receptor type of sensory nerve endings. Whole EN activity was not stimulated even by the highest dose (1 x 10(-1) M) of histamine when the nose was pretreated with saline, but was substantially stimulated by histamine in a dose-response fashion (1 x 10(-2) M) after pretreatment with HCI or H2SO4. Pretreatment with tripelennamine and HCl prevented the effect of histamine on the afferent EN activity; but after cimetidine and HCl pretreatment histamine still had a marked stimulant effect. In the case of single unit activities, histamine with HCl pretreatment had a long-lasting stimulatory effect (110.2 +/- 26.6 sec). It is concluded that the EN in guinea pigs include histamine-sensitive fibers whose sensitivity is mediated by H1 receptors and can respond to histamine only under abnormal conditions of the nasal mucosa.
The purpose of this study is to determine the hemodynamic effects of spironolactone administration associated with an unrestricted sodium diet (salt 10 g) in patients with compensated cirrhosis and portal hypertension. We studied the hemodynamic changes following eight weeks of administration of either placebo (N = 6) or spironolactone (100 mg/day) (N = 6 Pugh-Child's A and 6 B). No significant changes were observed after the administration of the placebo. Spironolactone induced a significant reduction in the hepatic venous pressure gradient (HVPG) (-10.1 +/- 13.3%, P < 0.05), which was associated with a significant reduction of cardiac output (-11.5 +/- 9.3%, P < 0.01), plasma volume (-8.1 +/- 4.7%, P < 0.01), and wedged hepatic venous pressure (-10.5 +/- 11.6%, P < 0.05). There was no significant change in hepatic blood flow and there was no significant correlation between the change in the HVPG and the change in circulating plasma volume. A decrease in the HVPG greater than 10% was observed in eight of 12 patients (67%), defined as responders, at eight weeks. Six of six (100%) grade A patients and two of six (33%) grade B patients responded. This study demonstrated that spironolactone with an unrestricted sodium diet decreased the HVPG in grade A patients but did not significantly decrease the HVPG in grade B patients.
OBJECTIVE: Activating mutations of the ACTH receptor have not been previously described. We investigated a 69-year-old woman with normal blood cortisol but undetectable blood ACTH concentrations. The aim of this study was to evaluate her hypothalamo-pituitary-adrenal axis by measuring circadian variation in blood ACTH and cortisol, and by performing CRH and ACTH stimulation and dexamethasone suppression tests. We also examined biological activity of her circulating blood ACTH using bovine adrenocortical cell suspensions and ACTH receptor gene structure by Northern blotting analysis. RESULTS: Random plasma cortisol concentrations ranged from 182 to 328 nmol/l, while ACTH concentrations were always undetectable. After an intravenous bolus injection of human CRH 100 micrograms, plasma ACTH rose slightly, while plasma cortisol increased appropriately. ACTH stimulation tests revealed that a small amount of ACTH (5 ng/kg b.w.) had the maximal cortisol stimulatory activity, and even smaller amounts of ACTH (0.5 and 0.05 ng/kg b.w.) produced significant increases in cortisol levels. ACTH bioassay of the patient's plasma demonstrated weak biological activity in the HPLC fractions which corresponded to the band of synthetic human ACTH 1-39. The ACTH receptor coding region was amplified by polymerase chain reaction using the leucocyte genomic DNA. There were two base mutations; cysteine 21-->arginine and serine 247-->glycine in the sequences coding for the first extramembranous N-terminal domain and the third extramembranous loop of the ACTH receptor. CONCLUSIONS: This patient with normal blood cortisol but undetectable ACTH levels showed increased adrenocortical sensitivity to ACTH and two point mutations in the ACTH receptor gene. This study, therefore, reports a previously undescribed syndrome--ACTH hypersensitivity syndrome--and provides insights into the molecular mechanism of ACTH receptor action.