Biomedical subjects
Publications and source records attributed to Y Katsuta.
An association between dermatomyositis-polymyositis and malignancy has been reported. However, controversy exists regarding a direct causal relationship between the two diseases. We describe a patient who had the concurrent onset and parallel clinical course of dermatomyositis and malignancy, and discuss the possible mechanisms for the association of the two disorders.
An association between autoimmune disease and malignancy, in particular lymphoproliferative neoplasms, has been reported, as has an increased incidence of extrahepatic malignancy in primary biliary cirrhosis (PBC). Monoclonal immunoglobulin elevations in PBC are rare, and there have been only three cases in the literature of PBC associated with multiple myeloma. We describe a patient who was concurrently diagnosed as having PBC and multiple myeloma, and emphasize the need to consider myeloma when evaluating monoclonal gammopathy in PBC. We also discuss the possible mechanisms for the association of the two conditions.
The succinate dehydrogenase activity and cellular DNA content of human head and neck squamous cell carcinomas were examined, and the chemosensitivity and ploidy status were compared with histologic differentiation. The average decrease of enzyme activity in the poorly differentiated squamous cell carcinomas was significantly greater than that of well- and moderately differentiated squamous cell carcinomas. Statistically significant differences were also noted with relation to the original site of the primary tumor. The chemosensitivity of a tumor with DNA aneuploidy tended to be lower among the well- and moderately differentiated squamous cell carcinomas and higher among the poorly differentiated type. We conclude from this study that simultaneous analysis of the chemosensitivity and DNA ploidy will aid not only in selecting effective antitumor drugs but also in predicting changes in cellular characteristics during the course of disease.
To study the long-term effects of pharmacological combination therapy, a comparison was made of the haemodynamic changes in patients with cirrhosis and portal hypertension following a 4-week treatment of propranolol or nipradilol, a new nonselective beta-blocker with nitrovasodilating effect. Nipradilol (12 mg/dag, n = 12) significantly diminished wedged hepatic venous pressure (WHVP, 25 +/- 16%), the hepatic venous pressure gradient (HVPG, 20 +/- 12%), and estimated hepatic blood flow (EHBF, 18 +/- 16%). Propranolol (30 mg/day, n = 11) also caused a significant reduction in WHVP (22 +/- 21%) and HVPG (24 +/- 21%), but not in EHBF. The percentage of portal pressure reduction and the frequency of nonresponders did not differ between the nipradilol and propranolol groups. Both agents reduced heart rate by approx. 20%. Nipradilol, however, did not cause a significant reduction in cardiac index (CI) versus a 14% reduction by propranolol. Pulmonary capillary wedge pressure and central venous pressure, an index of preload, were decreased slightly in the nipradilol group. When nonresponders were excluded, there was a significant correlation of the percentage of reduction between WHVP and CI or systemic vascular resistance, in the nipradilol group. These results indicate that nipradilol may have potent hypotensive effects on portal hypertension, similar but not superior to propranolol. Nipradilol, at the dosage used in the present study, did not appear to exert a nitrovasodilating effect to enhance the portal pressure reduction induced by beta-blocking action.
Racemic all-trans-3-hydroxyretinal (3-OH-RAL) (1) was converted by a reaction with (-)-camphanic acid chloride (CpCl) into a diastereomixture of camphanates (2a) and (2b) which was separated by preparative high-performance liquid chromatography (HPLC) to give two esters (2a) and (2b) in pure state, respectively. Saponification of (2a) and (2b) independently afforded optically active (3S)- and (3R)-3-OH-RALs (3a) and (3b), respectively, whose absolute structures were determined by circular dichroism (CD) spectra. Racemic 3-OH-RAL was separated to two peaks by HPLC using chiral column (ChiraSpher, Merck). Cochromatography with authentic specimens (3a) and (3b) showed that the peak with a short retention time corresponded to (3R)-isomer and the other to (3S).
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We proposed a new experimental animal model for portal hypertension in the female Japanese white rabbit by an intraportal injection of DEAE-cross-linked dextran microspheres (100 +/- 25 microns in diameter). Histology of the liver revealed portal obstruction by the injected microspheres in almost all portal triads, resulting in a foreign body granuloma. A sustained elevation of the portal pressure by a mean of 36.7% as compared with the basal value was observed for at least eight weeks in association with the portal-systemic collateral circulation demonstrated by portography, the radioisotope labeled microsphere method and histological examination of the esophagus and the liver. The elevation in portal pressure in the eighth week was associated with an increase in the portal blood flow determined at the main portal trunk. This was in accordance with the forward theory of the pathogenesis of portal hypertension. Since this model appears to show the two main conditions characteristic of portal hypertension persistent elevation of portal pressure and both extra- and intrahepatic portal collaterals, mimicking those in humans, portal obstruction by injecting DEAE-cross-linked dextran microspheres into the portal vein of the rabbit could provide a versatile model for portal hypertension.
The effect of plasma volume contraction induced by a 4-wk administration of spironolactone or furosemide on the hepatic venous pressure gradient was evaluated in consecutively allocated patients with cirrhosis and no ascites. In the spironolactone group (n = 15), the hepatic venous pressure gradient decreased significantly (p less than 0.005), by 21.8%, with a significant contraction of circulating plasma volume (p less than 0.01). Although there were no statistically significant correlations between the change in hepatic venous pressure gradient and changes in circulating plasma volume or in simultaneously determined systemic hemodynamics, a significant negative correlation (r = -0.74, p less than 0.01, n = 12) between the hepatic venous pressure gradient change and the post-treatment plasma aldosterone levels was found. However, in the furosemide group (n = 10), the hepatic venous pressure gradient and circulating plasma volume did not significantly decrease. Our data demonstrated a significant reduction in the hepatic venous pressure gradient on a chronic administration of spironolactone, which may have been due to volume contractions in patients with cirrhosis and no ascites.
We studied the relationship between CA2/3 and CA1 subfields in the generation of stimulus train-induced bursting using in vitro hippocampal slices. Repeated stimulation to the stratum radiatum induced three types of epileptiform activities: afterdischarge bursts, spontaneous bursts and single stimulus-triggered bursts. In the intact slices, spontaneous bursts in CA3 preceded those in CA1, whereas afterdischarge bursts in CA3 followed those in CA1 when it was possible to distinguish differences in the burst onset. After transection between CA2/3 and CA1, neither spontaneous nor triggered bursts could be induced or maintained in isolated CA1, where only small afterdischarge bursts with a higher bursting frequency were observed. It was difficult to induce afterdischarge bursts by the tetani to the mossy fibers. Some of the mechanisms underlying the generation of these stimulus train-induced bursts are discussed.
We report a case of a 60-year-old female presenting a histologically proven polymyositis with multiple coronary arteriocameral fistulas draining into the left ventricle. The exact pathogenesis of coronary artery fistulas and their relation to polymyositis are not clear.
In 42 patients with compensated cirrhosis and 31 control subjects, blood flow (BF) and vascular resistance (VR) were measured at the forearm and calf, using a pneumoplethysmograph. In some of the subjects deep-body temperature (DBT) was also measured by the zero heat flow method. In cirrhosis, BF and DBT were significantly higher and VR was significantly lower in the forearm than in the calf. Corresponding differences were not observed in control subjects. When these indices of the forearm were compared between cirrhosis and controls, BF and DBT were significantly higher and VR was significantly lower in cirrhosis than in controls. In cirrhotics in whom the gradient between forearm BF and calf BF was 1 ml.dl-1.min-1 or more (forearm greater than calf), the vascular response of the forearm to cold stimulation was reduced, whereas in the remaining patients and in controls the forearm BF and VR responded significantly. These results suggest that there is a regional difference in peripheral circulation in cirrhotics, partly with participation of impaired sympathetic nervous activity, which may account for the selective distribution observed in the clinical manifestations of vascular spider, palmar erythema, and warm hand, inclined toward the upper extremities or the upper part of the body.
Between September 1981 and December 1987, 1023 palpable breast tumors were submitted for cytological evaluation by fine needle aspiration before surgery (carcinoma: 793 cases, benign breast diseases: 230 cases). Clinical factor relating to the success of the aspirations were evaluated. Cases were regarded as positive when patients had a grade IV or more rating by Papanicolaou classification. The sensitivity was shown to be 73% (578/793); the specificity being 98% (226/230). A significantly lower rate of positive cancer identification occurred in smaller tumors (less than 2 cm, P less than 0.01) or scirrhous carcinomas (P less than 0.05). The comparison of positive rates between the aspiration cytology (66%) and the stamp cytology (95%) in 258 breast cancers (P less than 0.01) indicates the limited value of cytological diagnosis of breast cancers by fine needle aspiration.
The effect of changes in body posture on estimated hepatic blood flow (EHBF) and various hemodynamic parameters was examined in 15 patients with compensated cirrhosis. EHBF and various hemodynamic parameters were first measured with the patients in the supine position, and then again 10 min after tilting to 45 degrees. EHBF was 1089 +/- 315 ml/min at supine and 1065 +/- 328 after tilting; the difference was not significant. However, the patients were then divided into two groups according to the magnitude of the decrease in EHBF after tilting, with those showing a decrease of 10% of more assigned to group B, and those showing a decrease of less than 10% assigned to group A. It was found that ICG (R15) and BSP (R45) were significantly higher in group A. Meanwhile, among hepatic and systemic hemodynamics, wedged hepatic venous pressure, hepatic venous pressure gradient, free hepatic venous pressure, cardiac index, systolic blood pressure, systemic vascular resistance, and stroke volume were found to have changed significantly after tilting. These results suggest that posture change has no effect on EHBF in compensated cirrhotic patients.
Using an in vitro method the authors have investigated whether 8-hydroxycarteolol.HCl(8-OH carteolol) and 8-OH carteolol with benzalkonium chloride affected intact isolated porcine corneas to the same or to a different degree as carteolol.HCl (carteolol) or carteolol with benzalkonium chloride. These ophthalmically used drugs were applied as solutions of varying concentrations to the epithelial surface only, to the endothelial surface only, or to both surfaces of porcine corneas. The resultant opacities were determined using an opacitometer. In general, 8-OH carteolol and 8-OH carteolol with benzalkonium chloride caused less opacity to develop than carteolol and carteolol with benzalkonium chloride. This suggests that 8-OH carteolol may be a safer drug than carteolol for ophthalmic use. It is very interesting to note that compounds with two nitrogens, e.g., 8-OH carteolol, caused greater opacity in the intact cornea when applied to the endothelial surface than when applied to both the epithelial and endothelial surfaces; however, compounds with none or one nitrogen caused greater opacity in the intact cornea when applied to both surfaces than when applied to the endothelial surface.
The penicillin G acylase gene cloned from Arthrobacter viscosus 8895GU was subcloned into vectors, and the recombinant plasmids were transferred into Escherichia coli or Bacillus subtilis. Both E. coli and B. subtilis transformants expressed the A. viscosus penicillin G acylase. The enzyme activity was found in the intracellular portion of the E. coli transformants or in the cultured medium of the B. subtilis transformants. Penicillin G acylase production in the B. subtilis transformants was 7.2 times higher than that in the parent A. viscosus. The A. viscosus penicillin G acylase was induced by phenylacetic acid in A. viscosus, whereas the enzyme was produced constitutively in both the E. coli and B. subtilis transformants carrying the A. viscosus penicillin G acylase gene.
The oral administration of 2-(1,3-dithiol-2-ylidene)-1-phenyl-1,3-butanedione (KZ-1026) to normal rats at doses of 50, 100 and 200 mg/kg/day for 3 days accelerated liver enlargement in association with a dose-dependent increase in the total amounts of protein, RNA and DNA in the liver. The liver weight at 24 hr after the third dose of 200 mg/kg reached 174% of the control. With respect to the effect on liver enlargement, KZ-1026 differed from phenobarbital, since KZ-1026, unlike phenobarbital, increased hepatic DNA content without significant effects on P-450 and aminopyrine-N-demethylase. Incorporation of [3H]thymidine into liver DNA was stimulated by a single dose of KZ-1026 (200 mg/kg), and it peaked at 24 hr post dose (18 times the control), followed by an increase in the number of liver nuclei. Liver growth was also accompanied by an increasing hepatic reserve cell mass, expressed by the capacity of eliminating exogenous galactose from the blood stream. Pretreatment with KZ-1026 (200 mg/kg/day) for 3 days significantly improved the survival rate of subtotally hepatectomized rats from 39% to 78%. These findings indicate that KZ-1026 accelerates hepatocyte proliferation, resulting in an enhancement of liver functional mass in normal rats.
Corneas isolated from the pig eyeball have been treated in vitro with varying concentrations of befunolol hydrochloride, in order to test the topical effect of befunolol on the cornea in terms of opacity. Experiments were carried out with the corneas treated as follows: intact, epithelium-removed, endothelium-removed, and both epithelium- and endothelium-removed. Solutions of the drug were applied to both epithelial and endothelial surfaces, to the epithelial surface only, or to the endothelial surface only. When the drug was applied either to both surfaces or to the endothelial surface only, there was a significant increase in opacity. However, when applied to the epithelial surface only, befunolol caused an insignificant increase in opacity as compared with that of control. It is suggested, therefore, that corneal opacity due to befunolol hydrochloride topically administered to the eye, is concerned mainly with the epithelium in cornea, since the drug is uncapable of passing barrier probably existing in surface layer of epithelium but it easily penetrates in corneal layers from endothelial side to attain reversely to epithelial cells. Thus, it is probable that the risk to induce opacity is minor in case that befunolol is topically given in drops to the eye.
Changes in portal pressure are regulated by changes in hepatic vascular resistance, which is normally under neurohumoral control, and portal tributary blood flow. Two theories on the pathophysiology of portal hypertension have been proposed: the 'backward flow' theory, in which portal hypertension is attributable to increased resistance to portal venous flow, and the 'forward flow' theory, in which increased splanchnic blood flow maintains portal hypertension despite extreme portal-systemic shunting. The sinusoidal abnormalities caused by an accumulation of collagen in the perisinusoidal space of Disse may induce increased resistance to blood flow in various pathological conditions of the liver. Non-cirrhotic portal hypertension results from not only relatively uncommon disorders prevalent mainly in Asia and tropical countries, but also from acute and chronic phases of relatively common liver diseases. Systemic hyperdynamic circulation, characterised by an increased cardiac output and a reduced peripheral vascular resistance, and splanchnic hyperaemia may develop as consequences of portal hypertension. Although the mechanisms of these changes are not clearly understood, portal-systemic shunting as well as some vasoactive substances, including prostaglandins, may be involved. The erosive and eruptive mechanisms are the two potential explanations for variceal bleeding. In the latter, pressure should not be viewed in isolation and other additive factors such as variceal size may be involved. Several new techniques of measuring variceal pressure and blood flow may improve understanding of the actual pathophysiology of variceal bleeding. Renal haemodynamic alterations secondary to the systemic circulatory changes produced by portal hypertension may occur. The geographical pattern of prevalence in disorders associated with portal hypertension is briefly described in this paper.