[Diagnosis of pancreatic cystic tumor].
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Cholangiopancreatography, Endoscopic Retrograde↗
Biomedical subjects
K Ohashi
Publications and source records attributed to K Ohashi.
Seasonal variation in serum total concentrations of cholesterol and protein in elderly subjects.
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Adult↗
Inhibition of endothelial cell prostaglandin H synthase gene expression by naproxen.
Naproxen is a potent anti-inflammatory drug whose action is attributed to inhibition of prostaglandin biosynthesis. In view of our recent discovery that aspirin and sodium salicylate are capable of reducing cellular levels of prostaglandin H (PGH) synthase mRNA, we have evaluated the effect of naproxen on PGH synthase protein and mRNA levels in cultured human umbilical vein endothelial cells (HUVEC). PGH synthase mRNA levels were quantified by a competitive polymerase chain reaction (PCR) assay; protein was assessed by Western blotting. Naproxen decreased the PGH synthase protein level in HUVEC in a concentration-dependent manner. It abolished entirely the 70 kDa PGH synthase subunit at 5 micrograms/ml. It appears more effective in blocking interleukin-1 inducible PGH synthase levels. Naproxen also inhibited the synthase mRNA level in a concentration-dependent manner; levels were reduced by 33% at 5 micrograms/ml and 60% at 30 micrograms/ml naproxen. These results indicate that naproxen, like the salicylates, inhibits PGH synthase levels in cultured endothelial cells either by inhibiting transcription of the PGH synthase gene or by destabilizing its messenger RNA.
Cells, Cultured↗
Primary structure of human thromboxane synthase determined from the cDNA sequence.
Polymerase chain reaction techniques have been used to isolate a cDNA clone containing the entire protein coding region of thromboxane A2 synthase (EC 5.3.99.5) from a human lung cDNA library. The cDNA clone hybridizes with a single 2.1-kilobase mRNA species in phorbol ester-induced human erythroleukemia and monocytic leukemia cell lines. A second cDNA, differing only by an insert of 163 base pairs near the 3'-end of the translated region, was also found to be present in the same library. The proteins predicted from both nucleic acid sequences include the three polypeptide sequences determined from amino acid sequencing of the purified human platelet enzyme, five potential sites for N-glycosylation, and a hydrophobic region that may serve to anchor the synthase in the endoplasmic reticulum membrane. The longer predicted protein, designated thromboxane synthase-I, contains 534 amino acids, with a Mr of 60,684, whereas the shorter protein, designated thromboxane synthase-II, contains 460 amino acids and has a Mr of 52,408. Although thromboxane synthase-II lacks the conserved cysteine that serves as the proximal heme ligand in the other cytochromes, significant sequence similarities exist among thromboxane synthase-I and -II and several P450s, particularly those in family 3. The overall amino acid identity is considerably less than 40%, making it likely that thromboxane synthase represents a previously undefined family of cytochrome P450.
Amino Acid Sequence↗
Diurnal effect on caffeine clearance.
Caffeine (300 mg) was given orally to nine healthy subjects at 10:00 AM (day trial) or at 10:00 PM (night trial) using a crossover design. Saliva was obtained at 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours after administration of caffeine. Urine was collected for 8 hours after caffeine dosing. Caffeine clearances in saliva during the day trial were not different from those in the night trial. No significant difference was observed in urinary molar ratios of metabolites (AFMU + 1X + 1U/17U) between the two trials. These data suggest that caffeine clearances in saliva do not vary with its administration time. Since caffeine clearances in plasma are reflected in the urinary ratios of caffeine metabolites, its clearance in plasma might also not be altered by the time of dosing.
Administration, Oral↗
Chronopharmacology of furosemide in the elderly.
The authors have previously reported the time-dependent change in the diuretic effects of furosemide, a loop diuretic agent, in young and middle-aged subjects. The current study was undertaken to examine an influence of aging on this chronopharmacologic phenomenon. Ten milligrams furosemide was given intravenously to 12 elderly subjects (greater than 70 years of age) at 9:00 AM (day trial) or at 9:00 PM (night trial) by a cross-over design. One-hour urine samples were collected for 3 hours after each administration, and urine volume and urinary excretions of sodium and furosemide were determined. Urine volume and urinary sodium excretion increased after furosemide administration. Contrary to the findings in the young and middle-aged subjects, no significant differences were observed in these parameters at any observation period between the day and night trials in the elderly subjects. Urinary furosemide excretion of the day and night trials did not significantly differ. These results suggest that the chronopharmacologic profiles of furosemide are altered in the elderly.
Aged↗
Malignant melanomas of the oral cavity: heterogeneity of pathological and clinical features.
Data on 35 patients with oral malignant melanomas were pooled and the pathological features and the clinical course were examined in detail. Of these 35 cases, 27 (77.1%) showed a two-phase growth pattern, with both a vertical and a radial growth phase. Moreover, these 27 cases were classified into three subtypes according to gross features of the vertical growth phase; nodular, flat elevated and ulcerated types. Almost two-thirds of the cases were of the melanotic type. Malignant melanomas without a radial growth phase were found in 8 instances, all of which showed a nodular growth pattern, 1 being of melanotic type and 7 amelanotic. Mean latent insidious periods were evaluated for the cases with different growth phases. Cases with a radical growth phase exhibited the longest mean latent period (35.7 months), and a median survival time of 23.5 months. Cases without a radial growth phase showed a short mean latent period (2.1 months), and a median survival time of 7.5 months. The thickness of invasion ranged from 2 to 9 mm. Although 77.1% of the cases depicted similar pathological patterns to acral lentiginous melanomas of the skin, oral malignant melanomas demonstrated heterogeneity in morphological features, developmental process and biological behaviour. The histogenesis of oral melanomas is briefly discussed.
Adult↗
A case of popliteal cystic degeneration with pathological considerations.
Adventitial cystic degeneration of the popliteal artery is seldom encountered; only 39 cases have been reported up to now in Japan. The pathogenesis of this disease remains controversial, and the authors describe a case in which the pathological findings differed from cases reported in the previous literature. The subject was a 74-year-old man admitted to our hospital complaining of intermittent claudication. The characteristic findings of cystic degeneration of the popliteal artery were uncovered by contrast-enhanced computed tomography (CT) and duplex sonography. The contrast-enhanced CT showed a low-density area and duplex sonography revealed a multi-lobulated low-echoic lesion. The Doppler signal of the low-echoic lesion could not be detected. While some cysts were found in the adventitia, they were mainly located in the media. The media also showed a remarkable decrease of smooth muscle cells and a prominent mucinous degeneration that had occurred circumferentially. These findings suggest that the medial degeneration noted had occurred prior to cystic formation. Because of this and other findings, we recommend the use of the term cystic degeneration of the popliteal artery in addition to the term cystic adventitial disease of the popliteal artery.
Aged↗
Effect of treatment at night with S-1452, a thromboxane A2 receptor antagonist, on the morning rise in platelet aggregation.
It is well known that platelet aggregation shows a morning rise, which may contribute to the increase in the onset of ischaemic heart diseases during the morning period. The present study was undertaken to determine whether nocturnal dosage with S-1452, a thromboxane A2 receptor antagonist, would blunt the morning rise in platelet aggregability. S-1452 50 mg or placebo were given orally to 8 healthy subjects at 10.00 h (day trial) or 22.00 h (night trial) according to a cross-over design. Plasma concentrations of S-1452 and its metabolites, bisnor-(+)-S-145 and tetranor-(+)-S-145, and platelet aggregation were determined during the 12-hour period following the dose. Mean plasma concentrations of S-1452, bisnor-(+)-S-145 and tetranor-(+)-S-145 during the absorption phase were lower after the nocturnal dose than after the morning dose. The maximum plasma concentration and area under the plasma concentration-time curve of the compounds were also lower and the time to the maximum concentration were delayed after the treatment at night. A morning rise in platelet aggregation was observed following placebo treatment. The inhibitory effect of S-1452 on platelet aggregation was observed at 3 hours and persisted for up to 9 h in both trials. The results suggest that S-1452 is absorbed more slowly after the nocturnal dose than after the morning dose. However nocturnal treatment with 50 mg S-1452 may blunt the morning rise in platelet aggregability.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
Time-dependent change in the effect of probucol in subjects with elevated cholesterol.
A time-dependent change in the cholesterol-lowering effect of probucol has been evaluated in 20 subjects with elevated cholesterol. Probucol 500 mg was given once daily at 07.00 h (day trial) or 19.00 h (night trial) for 3 months according to a crossover design. Fasting blood samples were obtained during the control period and at the end of each treatment period. Serum concentrations of total and HDL-cholesterol were significantly decreased by both the treatments with probucol [total cholesterol (mmol.l-1): control 6.58; day trial 5.41; night trial 5.10; HDL-cholesterol (mmol.l-1): control 1.35; day trial 1.06; night trial 0.96]. These parameters were significantly lower in the night trial than in the day trial. The data indicate that the cholesterol-lowering effect of probucol varies with its time of administration in subjects with elevated cholesterol.
Aged↗
Triplet pregnancy involving complete hydatidiform mole and two fetuses: genetic analysis by deoxyribonucleic acid fingerprint.
A case of a triplet pregnancy involving a dizygous twin pregnancy and a complete hydatidiform mole after therapy with human menopausal gonadotropin and human chorionic gonadotropin is reported. Two female fetuses, two placentas in one mass with two amnions and two chorions, and a tumor mass with a grapelike appearance were spontaneously delivered at 19 weeks of gestation. The deoxyribonucleic acid fingerprints of the two placentas and tumor tissue were compared with those of the parents. The fingerprints of the placentas showed patterns different from each other; however, all their polymorphic fragments could be traced back to either the father or mother. All polymorphic fragments of the tumor tissue were inherited only from the father (androgenesis). These results indicated that this triplet pregnancy involved a dizygous twin pregnancy and a complete hydatidiform mole.
Adult↗
Influence of renal denervation on chronopharmacology of furosemide in rats.
Our previous studies have suggested that the adrenergic nervous system is involved in the mechanism responsible for the time-dependent change in the urinary excretion of furosemide in rats. To examine a potential role of renal nerves in this phenomenon, renal denervation or sham operation was performed using unilaterally nephrectomized rats. Furosemide (30 mg/kg) was given orally at 12 am or 12 pm. Urine was collected for 8 hours after furosemide dosing, and urinary excretions of furosemide and sodium were determined. Urinary furosemide excretion and diuretic effects of the agent (urine volume and urinary sodium) were significantly greater at 12 am than at 12 pm in the sham-operated group of rats. However these administration time-dependent changes in urinary furosemide and its diuretic effects disappeared in the renal-denervated group of animals. These results suggest that the renal nerves contribute to the time-dependent changes in the urinary excretion of furosemide and its subsequent diuretic effects.
Administration, Oral↗
Daily variations in platelet aggregation and adhesion in healthy subjects.
Platelet aggregation is known to show a morning rise. The present study was undertaken to examine whether platelet aggregation and adhesion show a peak in the afternoon. Platelet aggregation stimulated by 4 microM of adenosine diphosphate, 1 micrograms/ml of collagen, 4 microM of epinephrine and 0.5 mM of arachidonic acid, and platelet adhesion determined by platelet retention on a glass bead column were measured for a period of 28-hour with an interval of 4 hours in 6 healthy subjects. Platelet aggregation in response to 4 different aggregating agents showed a bimodal daily variation with peaks in the morning and in the afternoon. However platelet adhesion only showed a peak in the morning. Previous studies have demonstrated the increases in the onset of acute myocardial infarction (MI) in the morning and afternoon periods. As enhanced platelet aggregation is involved in the development of acute MI, the present study suggests that the rise in platelet aggregation contributes to the increase in acute MI in the morning and in the afternoon. The present study suggests that the enhancement of platelet adhesion, which might be involved in thromboembolic events, may be another triggering factor for the onset of acute MI.
Adenosine Diphosphate↗
Chronopharmacological study of furosemide; (IX). Influence of continuous norepinephrine infusion.
Our previous studies have suggested that the adrenergic nervous system is involved in the mechanisms responsible for the time-dependent changes in the effects of furosemide in rats. To examine this hypothesis further, norepinephrine (150 micrograms/kg/hr) or its vehicle alone was infused subcutaneously by osmotic minipumps. Furosemide (30 mg/kg) was given orally at 12 am or 12 pm. Urine was collected for 8 hours after the agent, and urinary excretions of sodium and furosemide were determined. Urine volume and urinary excretion of sodium and furosemide were significantly greater at 12 am than at 12 pm in the vehicle-infused group of rats. However these administration-time-dependent changes in the effects of furosemide and its urinary amount disappeared in the norepinephrine-infused group of animals. Since chronic norepinephrine infusion is considered to disturb the axis of adrenergic nervous system, these data support the hypothesis concerning the mechanisms of this chronopharmacological phenomenon of furosemide.
Administration, Oral↗
Urinary excretion of furosemide in rats with HgCl2-induced acute renal damage.
To examine the influence of mercuric chloride (HgCl2)-induced acute renal damage on urinary excretion of furosemide, HgCl2 (1 mg/kg) or its vehicle alone was given intraperitoneally to Wistar rats. The following two experiments were done. Study I: Three percent body weight (b.w.) of 1% NaCl solution or furosemide (30 mg/kg) in 3% b.w. of 1% NaCl solution was given orally before and after HgCl2 treatment, and an 8-hour urine was collected. Study II: Furosemide (30 mg/kg) was given orally, and blood samples were obtained at 1, 2, 3, 4, 6 and 8 hours after administration. Urinary excretion of N-acetyl-beta-D-glucosaminidase increased, and urine volume and urinary excretions of furosemide and sodium decreased in the HgCl2-treated rats. There were significant correlations between the urinary furosemide and its diuretic effects. Regression lines after HgCl2 were significantly different from those before treatment. The values of absorption as well as elimination rate constant were smaller, while the time to maximum concentration and the elimination half-life were longer in the HgCl2-treated rats compared to vehicle-treated animals. These results suggest that the urinary excretion of furosemide and the responsiveness of renal tubular cells to this agent are impaired in rats with HgCl2-induced acute renal damage.
Acute Kidney Injury↗
The fetus as an allograft: immunobiologic role of human trophoblasts for fetal survival.
OBJECTIVE: The hypothesis of this study is that trophoblasts contribute to the survival of the mammalian fetal allograft. STUDY DESIGN: Immunologic and molecular biologic studies were performed with human trophoblasts or trophoblastic tumor cells to investigate the expression of class I human leukocyte antigens, the susceptibility to natural killer and lymphokine-activated cells, the ontogeny of Fc gamma-receptors, and the production of immunosuppressive factors. RESULTS: Heterogeneous expression of class I human leukocyte antigens on trophoblasts was regulated at transcriptional level. Trophoblasts showed low susceptibility to natural killer and lymphokine-activated cells. Trophoblasts expressed natural killer cell-type Fc gamma-receptor III, which mediates phagocytosis. The trophoblast-derived immunosuppressive factor was very similar to transforming growth factor-beta. CONCLUSION: The trophoblasts, which ultimately form the fetoplacental interface, constitute a major immune barrier for the survival of the allogenic conceptus.
Female↗
Cervical discs are most susceptible to beta 2-microglobulin amyloid deposition in the vertebral column.
Intervertebral discs of 41 chronic renal failure autopsy cases were examined histologically and immunohistochemically to assess the distribution of beta 2-microglobulin-associated (beta 2m) amyloid in the vertebral column. The results demonstrated beta 2m amyloid to appear first in the cervical discs, then in the lumbar and upper thoracic discs, and finally in the middle and lower thoracic discs as the dialysis period is prolonged. The shortest dialysis period for which beta 2m amyloid was detected was one year and seven months. Deposition of beta 2m amyloid was most remarkable in the C4-5, 5-6, and 6-7 levels, which are known to sustain severe mechanical stress in daily life. Thus it is suggested that local mechanical stress accelerates beta 2m amyloidosis. A marked macrophage reaction was observed around the amyloid in cases of severe amyloidosis, the macrophages themselves being immunohistochemically positive for IL-1 beta and TNF-alpha. Amyloid deposition and reactive inflammation mediated by cytokines appear to be closely related to the pathogenesis of destructive spondyloarthropathy.
Adult↗
Production of multiple growth factors by a newly established human thyroid carcinoma cell line.
A multiple growth factor-producing tumor cell line (NIM-1) was newly established from a patient with thyroid cancer and remarkable neutrophilia. NIM-1 cells also caused severe neutrophilia in nude mice bearing tumors. NIM-1-conditioned medium (NIM-1CM) contained activities that supported not only granulocyte, macrophage and eosinophil colony formation of human bone marrow cells but also the growth of colony-stimulating factor (CSF)-dependent cell lines, NFS60-KX and TF-1. Northern blot hybridization analysis revealed the constitutive expression of granulocyte-CSF (G-CSF), granulocyte/macrophage-CSF (GM-CSF) and interleukin(IL)-6 mRNAs in NIM-1 cells. Enzyme-linked immunosorbent assays (ELISA) using NIM-1CM also confirmed the production of IL-1 alpha and a small amount of IL-1 beta besides G-CSF, GM-CSF and IL-6 in NIM-1 cells. In addition, unexpected production of IL-11 in NIM-1 cells was detected by northern blot hybridization analysis and by bioassay using an IL-11-dependent cell line. Therefore, NIM-1 cell line is shown to produce multiple cytokines including potentially megakaryopoietic growth factors such as GM-CSF, IL-6 and IL-11.
Adenocarcinoma, Papillary↗