[A measurement of V/V distribution by intravenous injection of Kr-81m and Tc-99m-MAA--a comparative study with Xe-133 inhalation method].
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Biomedical subjects
Publications and source records attributed to Y Ohtani.
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Proliferation and IgG synthesis of peripheral blood mononuclear cells (PBMC) in response to stimulation with recombinant interleukin 2 (IL-2) and Staphylococcus aureus Cowan 1 (SAC) were evaluated in 32 patients with chronic persistent hepatitis (CPH), chronic active hepatitis (CAH) and liver cirrhosis (LC). Eleven patients had serum HBe antigen, 10 presented with HBe antibody and 11 had non-A, non-B hepatitis. IgG synthesis of PBMC induced with the two stimuli was significantly decreased in patients with CAH and LC when compared with that of controls. However, the generated amounts of IgG were not associated with the HB virus carrier state. B cells and T4+ cells were responsible for the diminished IgG synthesis in patients with CAH and LC when assessed by coculture experiments. On the other hand, proliferative response of PBMC to IL-2 and SAC were similar in controls and patient groups. These findings indicate that IgG production level of PBMC stimulated with IL-2 and SAC can reflect the severity of the underlying disease in chronic hepatitis patients.
Blood vessels in muscle biopsy specimens from 4 Duchenne muscular dystrophy (DMD) patients (including 3 at the preclinical stage) were examined by electron microscopy and compared with those in non-diagnostic biopsy specimens from age-matched controls and cases of other childhood neuromuscular disorders. The most striking feature was the blister-like swelling of vascular endothelial cells in the biopsied muscle specimens from the 3 preclinical stage DMD patients, which was observed in 23-39% of the small blood vessels examined. Other noticeable features in the preclinical DMD patients were: (1) replication of the basement membrane, there being more than 3 layers in 30% of the capillaries; (2) many degenerating and regenerating capillaries; and (3) platelet adhesion and aggregation in small blood vessels including small arteries and veins. Morphometric analysis showed that the capillary and endothelial cell areas were much greater in the preclinical DMD patients than in the controls or the cases of the other neuromuscular disorders. These phenomena strongly suggest an as yet undetermined process in blood vessels in preclinical DMD.
For sinusoidal gratings, two experiments were carried out to examine relation between simple reaction time and perceptual and response processes. First, the simple reaction time (RT) was measured as a function of grating contrast with spatial frequency as a parameter. Second, contrast threshold was determined as a function of exposure duration (ED). On the basis of the RT-contrast function and the ED-contrast threshold function empirically obtained, the difference between the RT and the ED was evaluated as a function of grating contrast. The RT-ED difference, in which the perceptual integration time was eliminated, was considered to reflect the transmission time, delay in the response process, and delay in the motor response. As the grating contrast increased, the RT-ED difference decreased rapidly at first, and then gradually, and finally leveled off. The RT-ED difference vs contrast function depended on spatial frequency. Based on the analysis of the characteristics of the RT-ED functions, the effects of grating contrast and spatial frequency on the simple RT could be ascribed to the changing contributions of the perceptual and the response processes.
An enzyme-linked immunosorbent assay was developed to detect serum antibody binding to liver membrane antigen derived from human hepatoma cell line SK-Hep-1. When we tested sera from 214 patients with this assay, IgM antibodies were detected in 100% of patients with acute type A, but not with type B or non-A, non-B hepatitis. IgM antibodies were also found in highest frequency (76%) and titer in patients with autoimmune chronic active hepatitis (CAH) among chronic liver disease groups. IgG antibodies occurred in over 50% of patients with acute type A hepatitis, type B chronic active liver disease (CALD), and autoimmune CAH. IgA antibodies were present in 43% of the patients with alcoholic liver disease, but were also seen in other patient groups. When freshly isolated rat hepatocytes were used as target cells, prevalences and titers similar to those obtained with SK-Hep-1 were found. The levels of serum membrane binding antibody were significantly reduced by the addition of human liver-specific membrane lipoprotein in all patient groups. In particular, IgM antibodies became negative in over 50% of patients with CALD (both type B and non-A, non-B) and autoimmune CAH, whereas in acute hepatitis over 50% lost their positivity for IgG antibody. These results indicate that circulating liver membrane binding autoantibodies are heterogeneous, occurring in hepatitis virus-induced acute and chronic liver disease as well as in autoimmune CAH.
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Early-phase pyrogen tolerance was induced in rabbits by two consecutive daily injections of 125 ng of endotoxin per kg of body weight. The second injection of the same dose of endotoxin evoked only a monophasic fever with a peak response 1.5 h after the injection; no second peak was observed. The rabbits were released from the tolerance to develop a typical biphasic fever by an injection of 125 ng of endotoxin along with human beta interferon (HuIFN-beta), although the tolerance-inducing amount of endotoxin alone could not. The profile of the febrile response of tolerant rabbits injected with both endotoxin and HuIFN-beta could not be distinguished from that of normal rabbits. There was no essential difference between natural and recombinant HuIFN-beta in breaking tolerance. Heat-stable (70 degrees C, 30 min) endogenous pyrogen or tumor necrosis factor was increased significantly in concentration in the serum of tolerance-broken rabbits. These results suggest that HuIFN-beta stimulates the production of tumor necrosis factor in tolerant rabbits to elicit the second peak of febrile response.
Carnitine status was evaluated in 8 patients with partial ornithine transcarbamylase (OTC) deficiency and 19 patients with secondary carnitine deficiency, who were used as positive references. Laboratory findings indicated that all patients with OTC deficiency had secondary carnitine deficiency especially in hyperammonemic attack. After L-carnitine administration in 2 patients with OTC deficiency, the number of attacks was significantly reduced in both cases.
Five patients with mitochondrial disorders in a single family showed marked heterogeneity of clinical signs and symptoms. Two patients had the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes; one had blepharoptosis, seizures, and diabetes insipidus; and two had a nonspecific encephalomyopathic disorder. This family supports the concept of a "mitochondrial cytopathy."
Acute hemodynamic changes induced by two beta-blocking agents, bunitrolol and propranolol, in patients with ischemic heart disease were studied. Besides possessing negative chronotropic and inotropic effects which were demonstrated by decreased heart rate (HR), cardiac index (CI) and double product (DP) of the heart, propranolol significantly increased systemic vascular resistance (SVR, 12%, p less than 0.05) and the time constant of left ventricular (LV) isovolumic pressure fall (T, 10%, p less than 0.01). With bunitrolol, no significant changes were observed in indexes reflecting chronotropic and inotropic states of the heart, and CI and DP were essentially unchanged. Only LV systolic pressure (-5%, p less than 0.01), LV end-diastolic pressure (EDP, -17%, p less than 0.01) and T (-10%, p less than 0.05) decreased significantly. Systemic vascular resistance (SVR) decreased, though insignificantly. Myocardial oxygen supply-demand balance in the resting state was not improved by propranolol as evidenced by the fact that CI decreased in proportion to the decline in DP. In contrast, ischemia at rest was apparently improved by bunitrolol because LV wall stress decreased due to the reduction in LV volume which was suggested by the decline in LV systolic pressure and LVEDP while CI remained constant. Improvement of the time constant T might be strong evidence of relief from ischemia. Bunitrolol might be effective even in patients with overt heart failure, especially that due to ischemic heart disease because of its lack of negative inotropic action and its ameliorating effect on ischemia at rest.
Natural killer (NK) and activated killer (AK) cells appear to be important in immunoregulation, elimination of virus-infected cells and resistance to tumours. NK activity against K 562 and AK activity against FL target cells of peripheral blood mononuclear cells (PBMC) from patients with chronic persistent hepatitis (CPH), chronic active hepatitis (CAH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC) were investigated using 51Cr release assay. Spontaneous NK activity of patients with LC (P less than 0.05) and HCC (P less than 0.001) was decreased when compared to that of controls. The sera and PBMC from patients with low NK activity had no inhibitory effect on the NK activity of normal subjects. Indomethacin treatment significantly enhanced the NK activity of controls (P less than 0.05), whereas the drug did not affect that of patients with low NK activity. The percentages of PBMC that reacted with monoclonal antibodies anti-Leu-7 and anti-Leu-11a were similar in controls and patients. However, a Leu-11a+/Leu-7+ ratio, and NK activity of Leu-11+ and Leu-7+ cell-rich populations were significantly decreased in cirrhotic and HCC patients when compared to controls. Interleukin 2 boosted both NK and AK activities of patients, but to a lesser degree in comparison with those of controls when similarly stimulated. gamma-Interferon also significantly augmented NK and AK activities of patients, but the levels of cytotoxicity were lower in HCC patients (P less than 0.05) than those of controls. These findings suggest that the decreased NK and AK activities in chronic liver disease and HCC are due to an altered subpopulation ratio of NK cells and a functional defect of effector cells.
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A purified capillary permeability increasing-enzyme was obtained from Agkistrodon caliginosus venom by modification of our previous purification method. The purified enzyme, which had arginine esterase activity and strong capillary permeability increasing-activity, did not show caseinolytic, clotting or bradykinin-releasing activities. These properties of the enzyme were almost the same as those of the enzyme obtained by the previous purification method. When a mixture of the purified enzyme and bovine plasma or heated bovine plasma was injected into depilated skin on the back of a rabbit, the capillary permeability increasing-activity was much greater than that induced by injection of the enzyme alone. The substance which increases the capillary permeability was extracted from the incubated mixture of bovine plasma and the enzyme with 50-70% ethanol. Its activity was lost on treatment with carboxypeptidase A. From these results, it is supposed that the increase in capillary permeability induced by the enzyme is due to a low molecular weight peptide released from a protein in bovine plasma by the proteolytic action of the enzyme.
Biopsies of the biceps muscle and sural nerve were taken from a girl aged 2 years with infantile neuroaxonal dystrophy (INAD). In addition to the typical axonal spheroid bodies in a number of the i.m. nerve fibers, the neuromuscular junctions (NMJs) and motor nerve endings also contained axonal swellings. The sural nerve, except for three dystrophic fibers, was almost completely normal. A teased nerve preparation showed four additional abnormal fibers with focal axonal enlargement similar to those in giant axonal neuropathy (GAN). These results suggest that a biceps muscle biopsy may be more useful than a sural nerve biopsy for the diagnosis of INAD, because the muscle contains abnormal peripheral nerves and NMJs in high frequency.
Free and acylcarnitine in serum and urine samples were measured in five patients with hyperammonemia associated with anticonvulsant therapy including sodium valproate, of whom three had a Reye-like syndrome. All had considerable reduction in serum free carnitine and slight increase of acylcarnitine concentrations, suggesting increased conversion of free to acylcarnitine by valproate administration. Urinary excretion of both free and acylcarnitine was increased, accompanied by depressed reabsorption of free carnitine and decreased acylcarnitine/free carnitine clearance ratio. These results indicate a decreased threshold for free carnitine. The combination of these several factors may be responsible for carnitine deficiency in patients with hyperammonemia taking valproate.
We reported a 6-year-old girl with mitochondrial cytopathy with lactic acidosis. The patient developed hypotonia, hearing loss, mental retardation, short stature, cataracta, hypoparathyroidism, DeToni-Fanconi-Debré syndrome and carnitine deficiency. Histological examination disclosed ragged red fibers and moderate lipid storage in skeletal muscle tissue and several structural abnormalities of mitochondria both in muscle tissue and proximal renal tubules. Biochemical examination of muscle tissue revealed a partial deficiency of pyruvate dehydrogenase complex and normal activities of cytochrome c oxidase, succinate cytochrome c reductase and NADH cytochrome c reductase. This is the first report of mitochondrial cytopathy representing DeToni-Fanconi-Debré syndrome associated with partial deficiency of pyruvate dehydrogenase complex and normal cytochrome c oxidase activity.