Cimetidine reduces erythrocyte protoporphyrin in erythropoietic protoporphyria.
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Biomedical subjects
Publications and source records attributed to Y Hirano.
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Extracellularly applied ATP elicited a transient increase in intracellular free calcium concentration ([Ca2+]i) measured by fura-2 fluorescence digital imaging microscopy in isolated rabbit and guinea-pig atrial myocytes. In the electrophysiological study, ATP induced a transient depolarization of the membrane potential due to activation of a rapidly desensitizing inward current. Our results indicate that in mammalian atrial myocytes, ATP evoked transient increase in [Ca2+]i through release of internally stored Ca2+ associated with inflow of external Ca2+, mainly through L-type Ca channels which were voltage-activated secondarily to ATP-induced conductance changes.
A 60-year-old man with poorly controlled bronchial asthma was proposed for an emergency appendectomy. His preoperative chest X-P revealed that his left lung was completely collapsed with pneumothorax, but its onset was unclear. Following the left thoracocentesis, appendectomy was performed under general anesthesia (oxygen-halothane). About one hour after the thoracocentesis, pinkish foamy tracheal secretion was massively drained and its protein concentration was 3.8 g.dl-1.PaCO2 was 95 mmHg and PaO2 was 69 mmHg (FIO2 1.0). His chest X-P showed signs of pulmonary edema in his left lung and infiltrating shadow was observed in his right lung. IMV with PEEP, aminophylline and prednisolone improved his respiratory status and on the 11 th day he was weaned from the respirator. In a case of pneumothorax with unclear duration like ours, it is necessary to consider the possibility of the reexpansion pulmonary edema.
A 5-year-old boy with left side optic neuritis, which manifested itself 21 days after the onset of rubella eruption, is reported. Seven days after the onset of rash which persisted for 3 days, he was found to be excessively somnolent and disoriented, and a diagnosis of rubella encephalitis was made at our clinic. Clinical symptoms spontaneously subsided 3 days later. Twenty-one days after the appearance of rash (16 days after the onset of encephalitis) he complained of left frontal headache and blurred vision of left eye. The funduscopic examination revealed the left papillitis. Pattern reversal VEP (PVEPs) evoked by stimuli of left eye showed absence of N75 wave, and a prolonged conduction time and low amplitude of P100 wave. Corticosteroid therapy improved his complaints, funduscopic and PVEPs findings. When the treatment was stopped, the funduscopic findings were exacerbated but were improved soon again by the additional corticosteroid therapy. A delayed onset of optic neuritis after the initial infection and a prompt response to corticosteroid therapy may suggest an involvement of some autoimmune process in the pathogenesis of postinfectious optic neuritis in our case.
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The efficacy of examining antinuclear antibody (ANA) was investigated as a screening test detecting subclinical immune disorders in infertility and sterility. ANA was measured in 116 unexplained infertile or sterile patients. The ANA positive rate was 43.5% in group A (habitual abortion, n = 23), 38.1% in group B (consecutive miscarriages, n = 21), 30.0% in group C (one miscarriage, n = 10), 16.7% in group D (one or more deliveries n = 12) 22.0% in group E (primary sterility, n = 50), and 22.4% in the control group (n = 54). The positive rate for all the infertile patients (group A+B) was 40.9% and significantly higher than that in for the control group (p < 0.05). Ten patients with positive ANA had 12 deliveries and 20 patients with negative ANA had 23 deliveries. The frequency of preeclampsia in the patients with positive ANA was higher than in those with negative ANA (41.7% versus 4.3%, p < 0.05). A higher incidence of premature deliveries was recognized in the patients with positive ANA than in those with negative ANA (41.7% versus 8.7%, p < 0.1). Average birth weight (> 35 week) for patients with and without positive ANA was 2,976g (n = 8) and 3,122g (n = 19) respectively. The former tends to be smaller than the latter (p < 0.1).
It has been reported that tumour necrosis factor-alpha (TNF-alpha) is capable of inducing vascular injury, and interleukin 6 (IL-6) of inducing production of acute phase proteins and the maturation of megakaryocytes. Kawasaki disease (KD) is a systemic vasculitis with severe inflammation. We investigated whether TNF-alpha and IL-6 activities in serum from patients with KD differs from those in anaphylactoid purpura (AP) and measles. Serum TNF-alpha levels were measured by a sandwich enzyme immunoassay and IL-6 activities in serum were assessed by a colorimetric assay. Both KD and AP patients but not patients with measles had increased serum TNF-alpha levels during the acute stage. With respect to IL-6, patients with KD and measles, but not AP, had increased IL-6 activities in serum during the acute stage. IL-6 activities in serum of KD patients correlated with serum C-reactive protein levels and correlated to some extent with maximum platelet counts during the course of illness. These results suggest that KD differs from AP and measles regarding both cytokines. The combination of TNF-alpha, which may be responsible for severe vascular injury, and IL-6, which may be responsible for severe inflammation, may play an important role in acute KD.
To evaluate bone metastasis from hepatocellular carcinoma (HCC), both bone and 99mTc-HM-PAO scintigraphies were performed in six patients with clinically and pathologically confirmed HCC. Two patients had a bone scintigram which revealed abnormal accumulation in the skull base, pelvic bone and thoracic spine. The 99mTc-HM-PAO scans of both these patients also showed abnormal accumulation in the same sites. The bone scintigrams in one patient revealed not only abnormal accumulation in the ribs but also photon deficient areas in the sternum, thoracic spine and femur, while 99mTc-HM-PAO scans showed abnormal accumulation in all these sites. In three patients, bone scintigraphy revealed photon deficient areas in the ribs, pelvic bone and femur, and their 99mTc-HM-PAO scintigrams showed abnormal accumulation in the same sites. Thus, it was shown that, in the detection of bone metastasis from HCC by means of bone scintigraphy, it was necessary to pay attention to hot and cold lesions, and that a combination study with 99mTc-phosphorous compounds and 99mTc-HM-PAO was useful in evaluating these lesions.
Possible arrhythmogenic effects of the isoproterenol-activated Cl- current were examined in isolated guinea-pig ventricular myocytes under various intra- and extracellular Cl- concentrations. Experiments were carried out with external K+ concentration ([K+]o) decreased to 2 or 3 mM. Under symmetrical concentrations of Cl- in intra- and extra-cellular solutions (ECl = 0 mV), 1 microM isoproterenol (ISP) depolarized resting membrane potential (RMP) by 6.2 +/- 1.1 mV and slowed repolarization with induction of early afterdepolarizations (EADs) in 9 out of 9 cells. EADs appeared at voltages positive to -40 mV, where L-type Ca2+ current is assumed to be activated. When Cl- concentrations were settled near physiological conditions (ECl = -40 - -50 mV), ISP depolarized RMP by 2.8 +/- 0.4 mV and elicited abnormal repolarization with occasional EADs in 6 out of 19 cells. When ECl was set to -80 mV, however, ISP depolarized RMP by only 0.5 +/- 0.5 mV without induction of abnormal activities. Thus, depolarizing effects of ISP and incidence of repolarization abnormalities including EADs were increased as ECl shifted to more positive potential levels. At [K+]o = 4 mM, no abnormal activities were observed when ECl was around -50 mV (0/8), and 6 out of 6 cells showed abnormal activities when ECl was set to 0 mV. ISP-elicited abnormal activities were abolished by 1 mM DNDS (4,4'-dinitrostilbene-2,2'-disulphonic acid), a blocker for Cl- channels.(ABSTRACT TRUNCATED AT 250 WORDS)
FK506, a new immunosuppressant, caused glucose intolerance in rats given daily oral doses of 1, 5, or 10 mg/kg/day for 14 days, but did not induce hyperglycemia under normal feeding. Besides the glucose intolerance, insulin secretion was impaired and insulin levels in the pancreas were lowered. Histopathologically, there was vacuolation of the Langerhans islets in the animals given 10 mg/kg. After withdrawal of the drug, these changes in pancreatic function and morphology returned to normal within 2 weeks. The findings indicate that FK506 caused dose-dependent but reversible islet toxicity in rats.
The effects of FK506 on exocrine function of the pancreas in Sprague-Dawley rats were examined and compared with those of cyclosporine. FK506 did not affect the levels of amylase and lipase in the pancreas of rats given the drug orally in a daily dose of 1 or 5 mg/kg for 2 weeks. Furthermore, the pancreas of the rats showed good exocrine secretion of enzymes such as amylase and lipase on stimulation with carbachol in vitro. Cyclosporine 50 mg/kg given in the same way as FK506 also was free of effect on enzyme levels in the rat pancreas, but the exocrine secretion of the enzyme from the pancreatic lobules on stimulation with carbachol was impaired. It is concluded that FK506 does not affect pancreatic exocrine function in rats.
The presence of mutations in the p53 gene was examined in ovarian cancers by a polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. The primers were designed to amplify exons 5 through 9 that contain phylogenetically conserved domains of the p53 gene. Mutations were detected in 5 out of 10 cases, one of which contained a deletion in the second allele. A single base substitution was detected in 4 cases at codons 162, 175, 205 and 273 and a single base insertion in one case within codon 315. A high frequency of p53 mutations in ovarian cancers and lack of mutation in 6 benign ovarian tumors and 2 normal ovaries suggested that the mutation of the p53 gene was associated with the genesis and/or progression of ovarian cancer. In 1 of 7 endometrial cancers, two mutations at codons 239 and 254 were detected.
Usefulness of gadopentetate dimeglumine in magnetic resonance (MR) imaging of uterine neoplasms was evaluated in 53 patients with endometrial carcinoma and 15 patients with cervical carcinoma. T1- and T2-weighted MR images were obtained before the contrast material was administered. After a bolus injection of gadopentetate dimeglumine, dynamic MR images were acquired, followed by static T1-weighted images. Gadolinium-enhanced MR images revealed relatively small endometrial carcinomas in the uterine cavity as high signal intensity in four cases and invasion of the myometrium as low signal intensity in 20 cases. In eight cases, endometrial tumors showed irregular, early enhancement compared with that of the myometrium on dynamic images; these cases were associated with poor prognosis. Tumor extension into the lower part of the uterus, parametrium, and paracervical fat was well seen on enhanced images in cases of cervical carcinoma. The authors believe that gadolinium-enhanced MR imaging will prove helpful in the staging of uterine neoplasms.
The activation and inactivation relations of several ion channel currents overlap, suggesting the existence of a steady-state or "window" current. We studied L-type Ca2+ channel window current in single cardiac Purkinje cells using a voltage-clamp protocol by which channels were first inactivated nearly completely during a long-duration depolarizing step, and then the recovery of Ca2+ current was observed during repolarizing steps into the L-type Ca2+ window voltage range. With these conditions, a small-amplitude inward Ca2+ current gradually developed after repolarization to voltages within the window but not after steps to voltages positive or negative to it. Window current was suppressed by Cd2+ (50 microM), nifedipine (1 microM), and nicardipine (1 microM), and it was augmented by isoproterenol (5 microM) and Bay K 8644 (1 microM). At voltages at which window current developed, L-type Ca2+ channels also recovered to a closed state from which they could be reopened by an additional depolarizing step. At voltages positive to the window range, channel recovery to a closed state(s) was absent, whereas at voltages negative to the window range, channel recovery to a closed state(s) increased, as expected from the "steady-state" inactivation relation. Our results provide direct measurement of L-type Ca2+ window current and distinguish it from other processes, such as slow inactivation. Our findings support the postulate that within a window there occur channel transitions from inactivated to closed states, and these channels (re)open, and this process may occur repetitively. Some physiological and pathophysiological roles for L-type Ca2+ window current are discussed.
Induction of endoreduplication (ERD) using Hoechst 33258 as well as colcemid was carried out in cultured neuroblastoma (NB) line cells. In these endoreduplicated cells, the majority of double minutes (DMs) appeared to take a diplochromosome like configuration to form a cluster consisting of four minute elements, assuming a complex DM. Sister chromatid differential staining (SCD) using 5-bromo-2'-deoxyuridine (BrdUrd) revealed the non-random distribution of the stained chromatids among four chromatids composing each diplochromosome, suggesting the occurrence of so-called "outside replication" of DNA strands during the process of ERD. The same pattern of differential staining was also found in the quadruple minutes of each endoreduplicated DM. Since DMs are acentric, the present results suggest that centromeres do not play any essential role in the formation of diplochromosomes observed in the conventional cytologic preparations and that centromeres are probably not responsible for the phenomenon of the "outside replication" of DNA strands.
The relationship between pulmonary hypertension and lesions was examined in 41 dogs infested naturally with heartworms, which consisted of 28 cases with pulmonary heartworm disease and 13 cases with caval syndrome. Pulmonary arterial pressure (PAP) was measured before and 1 or 7 days after heartworm removal with a flexible alligator forceps. In these dogs, lesions were examined after the last measurement of PAP. The mean PAP was 28.2 +/- 16.0 mmHg (10.9 to 81.4 mmHg in range) at post-removal phase. Pulmonary arterial intimal lesions, pulmonary thromboemboli, pneumonic lesions, tricuspid valvular lesions and mitral valvular lesions were macroscopically recognized in 95, 59, 39, 54 and 56% of cases, respectively. These lesions were classified by severity and the relationship with PAP was examined by the multiple correlation analysis. The multiple coefficient correlation was found the highest between PAP and thromboemboli, followed by mitral valvular lesion, tricuspid valvular lesion, and pneumonic lesion. There was no significant correlation between PAP and intimal lesions. The coefficient of determination showed the highest value in thromboemboli when one variable was used, and increased only very slightly when a variable of thromboemboli was added to those of other lesions. The cases with high PAP had fresh thromboemboli in large pulmonary arteries. From these evidences, it was concluded that thromboemboli following natural death of heartworm was the most important factor causing an increase in PAP and developing clinical signs in canine heartworm disease.
Cardiopulmonary function was examined in 18 dogs with serious chronic heartworm disease showing ascites, subcutaneous edema, prostration, weakness, jaundice and so on. After surgical heartworm removal from the pulmonary arteries, 10 dogs recovered (surviving group), and 8 dogs died or were euthanatized because of poor prognosis (nonsurviving group). The number of live heartworms residing in the pulmonary arteries of the surviving group tended to be larger than that in the nonsurviving group. At necropsy, severe pulmonary arterial lesions such as thromboembolism including dead heartworms, proliferative and villous lesions and intimal hyperplasia were noticed in all dogs examined, and tended to be severer in the nonsurviving group. Heartworm-coiling around the tricuspid valve chord was found in 1 dog of the surviving group and 4 dogs of the nonsurviving group. Before heartworm removal, there was no significant difference in the mean pulmonary arterial pressure (MPAP) between the surviving and nonsurviving group. Right atrial pressure (v-wave) was higher, and the cardiac index (CI) was lower in the nonsurviving group. Arterial oxygen tension was lower in the surviving group than in the heartworm-free group, and it was lower in the nonsurviving group than in the surviving group. Carbon dioxide tension was lower in the surviving group than in the heartworm-free group. Bicarbonate concentration (HCO3-) was lower both in the surviving and nonsurviving groups than in the heartworm-free group. One week after heartworm removal, MPAP decreased (P less than 0.05), and CI and HCO3- tended to increase in the surviving group.