Variations of the pancreatic ducts as a cause of chronic alcoholic pancreatitis; ansa pancreatica.
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Biomedical subjects
Publications and source records attributed to H Itoh.
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To investigate the antihypertensive efficacy of aerobic exercise therapy in essential hypertensives, 20 patients underwent eight weeks of cycle ergometer training at anaerobic threshold (AT) point. Cardiopulmonary exercise testings with ramp protocol were performed before and at two/four/eight weeks during the training period in order to determine AT and to evaluate the changes in blood pressure (BP), heart rate (HR), oxygen uptake (VO2; ml/min/kg), and O2 pulse (ml/min/beat) during exercise. 75g glucose tolerance test (OGTT) was measured before and after exercise therapy. The mean values of systolic blood pressure, oxygen uptake, O2 pulse, before and after exercise therapy were as follows: systolic blood pressure at rest = 160 +/- 19 mmHg and 135 +/- 11 mmHg, systolic blood pressure at AT = 195 +/- 13 mmHg and 180 +/- 10 mmHg, oxygen uptake AT = 12.0 +/- 0.9 ml/min/kg and 14.4 +/- 1.0 ml/min/kg, O2 pulse at AT = 6.8 +/- 1.5 ml/min/beat and 7.6 +/- 1.88 ml/min/beat. After exercise therapy, systolic blood pressure decreased (p less than 0.01), while O2 pulse and VO2 increased (p less than 0.01). Hyperresponse of serum insulin to glucose also improved. These results show that aerobic exercise therapy at AT level has beneficial effects on high blood pressure and improves exercise tolerance and hyperresponse of serum insulin to glucose without any complications.
The clinical and pathological features of siblings with infantile neuroaxonal dystrophy were reported. Early clinical symptoms were marked hypotonia in legs, mental regression and poor vision. Laboratory data were normal except for the mild elevation of GOT and LDH in serum and cerebrospinal fluid. MRI showed progressive atrophy of cerebellar vermis and brainstem. EEG showed a progressive increase in the amount and amplitude of the fast activities over the age of 3 years. Auditory brainstem response (ABR) showed progressive worsening with no response by 2 years and 6 months. Somatosensory evoked potentials (SEP) showed no cortical response by 4 years. Nerve conduction velocity (NCV) of both motor and sensory nerves was within normal limits. Pathologically, spheroid bodies were found in the axons of central and peripheral nerves, remarkably in brainstem and dorsal column. MRI, ABR and SEP findings were clinically useful, suggestive of the degeneration of brainstem.
We presented five cases of Crow-Fukase syndrome. Plasma cell hyperplasia or dyscrasia in bone marrow were recognized in all cases and localized bone lesion was seen in three cases. Thyroid dysfunction was seen in three cases; hyperthyroidism in one case and hypothyroidism in two cases, which was considered to be one of the characteristics though it has seldom been described in this disease. Two of four cases treated with prednisolone had good responses but two cases treated with interferon had no effect.
A 38-year-old man with diffuse endobronchial infiltration with non-Hodgkin's lymphoma (NHL) is reported. He was admitted to our hospital on November 1990 because of lymph node swelling. Physical examination on admission revealed left axillary, bilateral cervical and inguinal lymph node swelling. Chest and abdominal CT scan showed para-aorta lymph node swelling, mild splenomegaly and heterogeneous density of the liver, although hilar and mediastinal lymphadenopathy were not found. Microscopic examination of the biopsy specimen obtained from the right inguinal lymph node and liver revealed NHL (B cell lymphoma, diffuse, mixed type). After two courses of chemotherapy, a chest roentgenogram showed bilateral hilar lymphadenopathy and reticular shadows. CT scan demonstrated a thickening of the left main bronchus. Bronchoscopic examination revealed a small submucosal nodule in the left main bronchus on February 1991, from which the biopsy specimen revealed NHL infiltration similar to that of the lymph node. At follow-up bronchoscopic examination, in spite of chemotherapy, scattered NHL infiltration was found in the submucosal space of the left vocal cord, carina and the bifurcation between left upper and lower bronchi. In patients with NHL, endobronchial involvement is rare. In this case, diffuse endobronchial infiltration was not thought to be direct invasion from the lymph node but hematogenous or lymphatic spread to the bronchi.
Equine alpha 1-acid glycoprotein (alpha 1AG) was isolated from equine serum by successive ammonium precipitation, anion- and cation-exchange chromatographies, and gel filtration. Purified equine alpha 1AG had a molecular weight of 46,000 +/- 1,000, and contained 31.4% carbohydrate. Gel isoelectric focusing revealed an isoelectric point range of 2.8 to 3.7. With immunoelectrophoresis, it was found that alpha 1AG migrated to the alpha 1-globulin region. Single radial immunodiffusion was used for quantitative measurement of alpha 1AG in equine serum. In clinically normal foals, serum alpha 1AG was undetectable (less than or equal to 20 micrograms/ml) in less than or equal to 7-day-old foals, but was detected by 14 days. The alpha 1AG concentration (mean +/- SD) increased to reach mean adult values of 99.23 +/- 26.90 micrograms/ml by 1 year of age. The alpha 1AG concentration in pregnant mares decreased at 2 to 3 months before parturition, then gradually increased until 1 day after parturition, when a brief decrease was observed. The concentration increased again at 2 weeks after foaling, then a decrease was observed, after which the alpha 1AG concentration increased again by 2 to 4 months after parturition. The concentration of serum alpha 1AG quickly rose to peak values 2 to 3 days after castration and jejunojejunostomy in adult horses, returning to baseline values by 14 to 28 days after surgery. The alpha 1AG was concluded to be an acute-phase reactive protein in horses.
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The T2 relaxation times of 28 adrenal masses smaller than 5 cm obtained using a 1.5 Tesla MR imaging system were analysed to evaluate the ability of this parameter to characterize the tissue masses. The adrenal masses included 13 nonhyperfunctioning adenomas, five hyperfunctioning adenomas, five metastatic tumors, two pheochromocytomas, one nodular hyperplasia, one ganglioneuroma, and one cyst. The mean T2 value of nonhyperfunctioning adenomas was almost the same as that of hyperfunctioning adenomas. A significant difference was found in T2 (p less than 0.01) between nonhyperfunctioning adenoma (50 msec +/- 7 msec; mean +/- S.D.) and metastatic tumor (63 msec +/- 11 msec), whereas there was no significant difference in mass size between them. The two pheochromocytomas and the ganglioneuroma, which were derived from adrenal medulla, had relatively long T2 of over 70 msec. The T2 values of nodular hyperplasia and adrenal cyst were 58 msec and 123 msec, respectively. Although the T2 values of metastatic tumors tended to be longer than those of nonhyperfunctioning adenomas, differentiation between them with a T2 of 60 msec was not necessarily possible, especially in smaller masses. The T2 values of two metastatic tumors of less than 2 cm indicated 50 msec levels. There seemed to be a correlation between mass size and T2 in metastatic tumors. In adenomas, however, no significant correlation was demonstrated. We conclude that the characterization of small adrenal masses by T2 at 1.5 Tesla is unsatisfactory in differentiating metastatic tumors from nonhyperfunctioning adenomas.
Recovery of hydrophobic proteins from an RP-HPLC column was improved using a fast-separation RP-HPLC system operated at room temperature. Hydrophobic proteins such as ovalbumin could be adequately eluted from a nonporous octadecylsilyl (C18) spherical silica gel with a particle diameter of 20 microns using steep gradient elution with a 0.1% aqueous trifluoroacetic acid-acetonitrile system at a constant flow rate of 4 ml/min. Recoveries improved under fast separation since the protein sample suffered only a slight amount of irreversible denaturation on the hydrophobic surface of the stationary phase. The fast-separation system was also applied to the separation of larger proteins such as apo-ferritin (443 kDa) and thyroglobulin (669 kDa) as well as egg white proteins.
A new cell line (LC-1/sq) of human lung squamous-cell carcinoma was established from a surgically resected specimen of primary lung cancer. Upon continuous propagation in serum-free culture medium, it secreted trypsin inhibitors into the conditioned medium. The major fraction of the trypsin inhibitor (T1-1) was purified to apparent homogeneity by anion-exchange and gel-filtration high-performance liquid chromatography (HPLC) and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) followed by transblotting to Immobilon. T1-1 effectively inhibited trypsin. Chymotrypsin, plasmin and kallikrein were inhibited to a lesser extent, but urokinase-type plasminogen activator, elastase, thrombin and papain were not inhibited. The activity of T1-1 was acid-stable and heat-resistant, and its molecular weight was 115 kDa by SDS-PAGE. It exhibited single NH2-terminal sequence, and its first 20 NH2-terminal amino-acid residues were identical with those of protease nexin-II (PN-II)/amyloid beta-protein precursor (APP). These characteristics of T1-1 suggest that the major trypsin inhibitor secreted by LC-1/sq is indistinguishable from PN-II/APP. LC-1/sq is the first lung squamous carcinoma cell line that secretes functionally active trypsin inhibitor, PN-II/APP, in vitro and is useful for studying its biological significance in malignant tumor.
The distribution and levels of expression of Gs alpha, Gi1 alpha, Gi2 alpha, Gi3 alpha, Go alpha, and Gx alpha mRNAs were compared by Northern blot analysis using several rat tissues and selected human and rat cell lines. Gi1 alpha, Go alpha, and Gx alpha, were detected in a limited number of tissue and cells whereas Gi2 alpha, Gi3 alpha, and Gs alpha, were expressed in all the tissues and cells tested albeit in varying amounts. The expression of these six genes appears to be differentially regulated during postnatal development of the rat brain. High expression levels particularly of Go alpha, in young rat brain may be related to the formation of neurites during differentiation of nerve cells.
To understand the physiological functions of the 105-kDa protein which is testis-specific and HSP90 (90-kDa heat-shock protein) related protein, the appearance of it in the testis has been followed during the development of rat. On immunoblotting analysis, the 105-kDa protein did not appear until after the age of five weeks, while HSP90 could be detected at three weeks. In the spermatozoa, the 105-kDa protein was much abundant but not in the LC-540 cells (a cell line from Leydig cell tumor in rat testis) cytosol. This finding has attracted much attention to the relationship between this protein and sperm functions.
We have constructed mutants of the alpha subunit of Gs in an attempt to identify sites in the protein that are important for its interaction with adenylylcyclase. Some residues specific for those G proteins that activate adenylylcyclase were replaced with residues characteristic of Gi alpha. Mutant proteins were expressed in Escherichia coli, and two of these were purified to homogeneity and characterized in detail. Mutation of trp263, leu268, or arg269 caused a significant loss of the capacity of Gs alpha to stimulate adenylylcyclase, and the triple mutant had less than 1% of the ability of wild type Gs alpha to activate the enzyme. Guanine nucleotide binding and GTP hydrolysis by the mutant proteins were unaltered, as was guanosine 5'-3-O-(thio)triphosphate-induced enhancement of intrinsic tryptophan fluorescence. Mutant proteins also appeared to have a reduced affinity for the G protein beta gamma subunit complex. Secondary structure analysis and comparison with the structure of p21ras suggests that the region of Gs alpha that we have identified is part of a loop that may be involved in interaction of the protein with adenylylcyclase. Although these residues are essential for activation of adenylylcyclase, they are not sufficient to do this when placed in the context of another G protein alpha subunit.
To evaluate the efficacy of enoximone on exercise tolerance in patients with mild to moderate heart failure, 33 patients underwent cardiopulmonary exercise tests before and 3 hours after placebo or after receiving 25 or 100 mg of enoximone administered randomly in a double-blind manner. The electrocardiogram was monitored and blood pressure measured every minute throughout cycle ergometer exercise testing with a ramp protocol in which the work rate increased 1 W every 6 seconds after a 4-minute 20-W warm-up. Minute ventilation, oxygen uptake (VO2), and carbon dioxide output were measured every 10 seconds in order to determine anaerobic threshold (AT) and peak VO2. Five patients were excluded from evaluation before breaking the double-blind key because of insufficient data. Heart rate increased and systolic blood pressure decreased throughout the testing only in the group taking 100 mg (n = 10). Significant increases in AT (14.4 to 16.2 ml/min/kg) and peak VO2 (20.8 to 22.9 ml/min/kg) were observed in the group taking 100 mg. The increases in AT showed a dose response, namely +0.7% in the placebo (n = 9), +6.9% in the 25-mg (n = 9) and 12.5% in the 100-mg group. The work rates at the AT point increased in the 25- and 100-mg groups. These results indicate that a single oral administration of enoximone improves exercise tolerance in patients with mild to moderate heart failure.
Ibopamine is an orally active derivative of dopamine (DA) which metabolizes to its active form, epinine. Epinine is one of the few catecholamines that possess dopaminergic--DA1 and DA2--activity, alpha 1, alpha 2, beta 1, and beta 2 activity, with indirect sympathomimetic action of dopamine. Ibopamine increased positive dP/dt, stroke volume, aortic blood flow, renal blood flow, and diuresis in animals. In healthy volunteers and patients with heart failure, a single oral dose of ibopamine showed primary vasodilating action (postsynaptic DA1 activity and presynaptic DA2 activity). Following a single oral dose of 100 or 200 mg of ibopamine, the plasma concentration of epinine reached its peak within 30 minutes, and declined rapidly so that concentration was not detectable after 1.5-3 hours. Pharmacokinetics and hemodynamic effects in congestive heart failure patients are also discussed.
Recent evidence suggests that vasoconstrictive substances, including angiotensin II (Ang II), may function as a vascular smooth muscle growth promoting substance and may contribute to vascular hypertrophy in hypertension. Atrial natriuretic polypeptide (ANP) is known to be a physiological antagonist to Ang II in blood pressure and fluid homeostasis. Moreover, we have demonstrated that ANP can attenuate Ang II's action on vascular hypertrophy. In this study, we investigated the potential molecular mechanisms for the interaction of ANP and Ang II on vascular cell growth. Ang II dose-dependently induced RNA synthesis in post confluent cultured rat aortic smooth muscle (RASM) cells. ANP (10(-7) M) inhibited the hypertrophic effect of Ang II at the concentration of 10(-10) - 10(-8) M) but exerted no effect on the action of higher doses (10(-7) - 10(-6) M) of Ang II. Ang II (10(9) - 10(-8) M) and a protein kinase C activator, phorbol 12-myristate 13-acetate (PMA, 10(-8) M) rapidly induced c-fos as well as c-Jun and Jun-B mRNA expression in RASM cells. ANP (10(-7) M) itself had no apparent effect on the expression of these protooncogenes. Furthermore, ANP did not inhibit the induction of these protooncogenes by Ang II or PMA. Paradoxically, ANP (10(-7) M) significantly enhanced c-fos mRNA expression induced by Ang II and PMA. However, the chloramphenicol acetyl transferase (CAT) assay using a CAT expression vector containing the AP-1 binding element showed that ANP had no effect on the basal and PMA-stimulated AP-1 activity in transfected RASM cells. We conclude, therefore, that the inhibitory effect of ANP on the growth of vascular smooth muscle cells in vitro does not occur through the regulation of these protooncogene expressions.
Go is a specific class ("other") of signal-transducing heterotrimeric GTP-binding proteins (G proteins) that is expressed in high levels in mammalian brain. We have cloned two different rat cDNAs encoding the alpha subunit of Go (Go alpha-1 and Go alpha-2) and a human Go alpha chromosomal gene. The human Go alpha gene spans more than 100 kilobases and contains 11 exons, including one noncoding exon in the 3' flanking region. The 5' flanking region is highly G + C-rich and contains five G.C boxes (Sp1 binding sites) but no TATA box. Exons 7 and 8 coding for amino acid residues 242-354 of Go alpha protein are duplicated (referred to as exons 7A, 7B, 8A, and 8B). It was found that exons 7A and 8A code for Go alpha-1, and 7B and 8B code for Go alpha-2. This indicates that two different Go alpha mRNAs may be generated by alternative splicing of a single Go alpha gene. The splice sites of the Go alpha-1 and Go alpha-2 genes are completely identical with those encoding human inhibitory G protein alpha subunits Gi2 alpha and Gi3 alpha [Itoh, H., Toyama, R., Kozasa, T., Tsukamoto, T., Matsuoka, M. & Kaziro, Y. (1988) J. Biol. Chem. 263, 6656-6664] and also transducin G protein alpha subunit Gt1 alpha [Raport, C. J., Dere, B. & Hurley, J. (1989) J. Biol. Chem. 264, 7122-7128]. Sequence homology and conservation of the exon-intron organization indicate that the genes coding for Go alpha, Gi2 alpha, Gi3 alpha, Gt1 alpha, and probably Gi1 alpha may be evolved from a common progenitor. Like Go alpha-1, Go alpha-2 is expressed mainly in brain.
To determine whether the paraventricular nucleus (PVN) contributes to the development of hypertension in spontaneously hypertensive rats (SHR), we compared cardiovascular responses to ganglionic blockade with hexamethonium or vasopressin antagonism with dPVAVP in sham-operated or PVN lesioned SHR and Wistar-Kyoto rats (WKY). Lesions were produced electrolytically when the rats were 5 weeks old. During the next 3 weeks, tail-cuff measurements showed that the development of hypertension in SHR was inhibited, while systolic pressure in WKY was unaffected. Mean pressures recorded directly from the femoral artery at 8 weeks of age were lower in lesioned than in sham-operated SHR (141 +/- 5 vs 110 +/- 3 mm Hg, P less than 0.05), but did not differ in corresponding WKY groups (110 +/- 4 vs 112 +/- 5 mm Hg). Depressor responses to ganglionic blockade induced by i.v. injection of hexamethonium (25 mg/kg) were significantly larger in sham-operated than in lesioned SHR (-41 +/- 4% vs -28 +/- 3%, P less than 0.05). By contrast, vasopressin antagonism with dPVAVP did not alter blood pressure in all rat groups. In 24-h urine samples, excretion of vasopressin was unaffected, but that of norepinephrine was significantly reduced in lesioned SHR. These findings suggest that the PVN contributes to the development of spontaneous hypertension by sympathetic activation without increasing vasopressin secretion.