In vivo proton magnetic resonance spectroscopy in adult Down's syndrome.
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Adult↗
Biomedical subjects
T Horie
Publications and source records attributed to T Horie.
Evaluation of adriamycin-induced lipid peroxidation.
Lipid peroxidation is known to be a mechanism for Adriamycin-induced toxicity. In the present study, two methods which detect fluorescent substances and high molecular weight protein aggregates in peroxidized membranes were applied to Adriamycin-induced lipid peroxidation in liver microsomes. A rat liver microsomal suspension containing an NADPH-generating system was incubated with Adriamycin. Thiobarbituric acid reactive substances (TBA-RS), formed during this incubation, were transferred from the microsomes to the medium. Fluorescent substances determined by the fluorescence emitted from both the microsomes themselves and the chloroform/methanol extracts of the microsomes, were found to be formed during this incubation. High molecular weight protein aggregates determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, were also formed. Fluorescent substances and high molecular weight protein aggregates were found in microsomal membranes themselves and increased time dependently. These substances retained in membranes can be of great use to delineate the site of Adriamycin-induced lipid peroxidation in vitro and in vivo and to determine how this lipid peroxidation affects the membrane.
Animals↗
Developmental aspects of a unique glutathione S-transferase subunit Yx in the liver cytosol from rats with hereditary hyperbilirubinuria. Comparison with rat fetal liver transferase subunit Yfetus.
The unique glutathione S-transferase (GST) subunit Yx, which is undetectable in normal adult rat liver cytosol, was shown to occur in the liver cytosol of rats with hereditary hyperbilirubinuria (EHB). The Yx subunit is a member of the Alpha-class GST subunits, and is immunologically closely related to the Yc subunit. The Yx subunit has an apparent M(r) of 26,400, different from those of Ya (M(r) 25,800), Yb1 and Yb2 (both M(r) 27,200) and Yc (M(r) 28,400). During postnatal development in livers of EHB rats, the Yx subunit concentration in either sex was highest during the first week post partum and declined rapidly with age. Although the concentration of subunit Yx at 8 weeks of age accounted for about 60% in females and 40% in males of that observed in 1-week-old 'neonatal' male EHB rats, concentrations in females thereafter increased gradually to almost the neonatal level and remained at this high level at least up to 37 weeks of age, whereas the concentration in males did not increase again. Thus the post-pubertal Yx subunit concentration was 2-fold higher in females than in males. In contrast, in normal Sprague-Dawley rat liver, the Yfetus subunit, with the same M(r) as the Yx subunit, had the highest concentration in 10-day-old animals, declined rapidly thereafter, and was not detectable in the post-pubertal period. The Yfetus subunit was also immunoreactive with an antibody against GST YcYc. The analysis of GST subunits by reverse-phase h.p.l.c. revealed that the Yx subunit was eluted at a retention time different from other known subunits, but coincided with that of Yfetus. The N-terminal amino acid sequence of the Yx subunit displayed a high degree of sequence similarity to that of the Yfetus subunit. These data suggest that the Yx subunit in EHB rats may be very similar to, if not identical with, the Yfetus subunit.
Amino Acid Sequence↗
Canalicular transport of reduced glutathione in normal and mutant Eisai hyperbilirubinemic rats.
We have characterized the transport of GSH and the mechanism for impaired GSH transport in mutant Eisai hyperbilirubinemic rats (EHBR) using isolated canalicular membrane-enriched vesicles (cLPM). In control animals, the transport of GSH is an electrogenic process and is trans-stimulated by preloading the vesicles with GSH and is not enhanced in the presence of ATP. GSH transport in cLPM is saturable with a single component having a Km of approximately 16 mM and a Vmax of 6.7 nmol/mg/15 s. EHBR is a Sprague-Dawley rat with hyperbilirubinemia due to impaired bile secretion of organic anions by the ATP-dependent organic anion/GSH-conjugate transporter. In cLPM from EHBR we confirmed the defective stimulation by ATP of the transport of LTC4 and GSSG. In the mutant cLPM, the characteristics and kinetics of GSH transport were the same as in the controls. 2,4-(dinitrophenyl)-glutathione (DNP-GSH), which is a substrate for the ATP-dependent canalicular organic anion carrier, in the absence of ATP, cis-inhibited the transport of GSH into cLPM vesicles; however, when the vesicles were preloaded with DNP-GSH, there was a dose-dependent trans-stimulation of GSH transport. In contrast, in the presence of ATP, DNP-GSH enhanced GSH transport in cLPM vesicles; at 0.25 mM DNP-GSH, a concentration which did not cis-inhibit GSH, addition of ATP resulted in accelerated GSH transport; at 1.0 mM DNP-GSH, cis-inhibition was completely reversed by the addition of ATP despite a negligible fall in the medium DNP-GSH. Interestingly, sulfobromophthalein-glutathione (BSP-GSH) neither cis-inhibited nor trans-stimulated GSH transport in cLPM. This contrasts with bLPM where BSP-GSH interacts with the GSH carrier. Therefore, GSH is transported into bile by a multispecific low affinity electrogenic carrier which is distinct from the multispecific high affinity ATP-driven organic anion transporter. Although both carriers have overlapping specificities, BSP-GSH and GSH are uniquely specific for only one of the carriers. The near absence of GSH in the bile of mutant rats can be best explained as a secondary defect due to cis-inhibition from retained substrates for the defective carrier and/or loss of trans-stimulation by these same substrates which normally are concentratively transported into the bile. Other possibilities such as change in GSH carrier activity upon isolation or loss of a negative protein regulator during membrane isolation, although theoretical alternatives are less easily reconciled with the defect in the ATP-driven organic anion transporter.
Adenosine Triphosphate↗
Fluorospectroscopic analysis of the fluorescent substances in peroxidized microsomes of rat liver.
The fluorescent substances formed in rat liver microsomes in the course of lipid peroxidation were investigated by fluorescence techniques. The fluorescence emitted from peroxidizing microsomes continuously increased as lipid peroxidation progressed, while the steady-state fluorescence anisotropy increased and then reached a plateau. A similar increase was observed in the steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene in peroxidizing microsomes. The fluorescence from peroxidized microsomes consisted of at least three species having short, middle or long fluorescence lifetimes. The lifetimes and relative amplitudes of fluorescence were unaffected by the extent of lipid peroxidation. Both fluorescence of the chromolipids extracted and the proteins isolated from peroxidized microsomes had the same characteristics in fluorescence lifetimes as the fluorescence from whole peroxidized microsomes. Thus, these lipids and proteins appear to be the major biological substances responsible for the fluorescence emanating from whole peroxidized microsomes. Furthermore, fluorescent substances formed in microsomes seem to increase in quantity rather than change in quality as lipid peroxidation progresses.
Animals↗
The monocyte tumor necrosis factor-alpha production in patients with acute leukemia in complete remission.
Tumor necrosis factor-alpha (TNF-alpha) production by unstimulated and lipopolysaccharide (LPS)-stimulated peripheral monocytes has been studied in 17 acute myeloid leukemia (AML) patients, 54 AML patients in complete remission (AML-CR), 9 acute lymphoblastic leukemia (ALL) patients and 13 ALL patients in complete remission (ALL-CR). TNF-alpha production by the unstimulated monocytes in ALL patients (n = 6, mean: 6.6 +/- 4.9 u/ml) was higher than that of normal controls (n = 13, 0.9 +/- 0.7 u/ml), AML patients (n = 14, 2.0 +/- 2.1 u/ml) and AML-CR patients (n = 21, 1.4 +/- 1.2 u/ml). TNF-alpha production by the LPS-stimulated monocytes of the AML-CR patients (n = 54, 12.4 +/- 13.4 u/ml) was significantly higher than that of the normal controls (n = 21, 3.5 +/- 2.5 u/ml) and the AML patients (n = 17, 2.6 +/- 2.4 u/ml), p < 0.01, but there were not any significant differences among the AML-CR patients and the ALL patients or the ALL-CR patients. We separated the AML-CR patients into 3 groups, depending on the length of their remission, and found that AML-CR patients with longer than 6 months (M) but less than 60 M (n = 21, 15.7 +/- 16.9 u/ml) and the patients with a remission longer than 60 M (n = 11, 18.2 +/- 15.9 u/ml) had significantly higher TNF-alpha production than that of the controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute Disease↗
Serum soluble CD4, CD8 and IL-2R levels in adult acute myeloid leukemia in remission.
We have measured the serum levels of soluble CD4, CD8 and IL-2R in 43 patients with AML in complete remission (AML-CR). The sCD8 levels of AML-CR patients (443.9 +/- 224.4 u/ml) were significantly high as compared to that of the normal controls (177.1 +/- 76.3 u/ml), p < 0.01. The sIL-2R levels of AML-CR patients were 715.0 +/- 646.3 u/ml, which significantly differed when compared to 322.1 +/- 65.7 u/ml for the normal controls, p < 0.01. However, the sCD4 levels of AML-CR patients were 9.6 +/- 4.7 u/ml, which did not differ from the 8.3 +/- 2.6 u/ml of the normal controls. The AML-CR patients showed significantly increased sCD8 and sIL-2R levels at all ranges during the remission from one to 188 months. The sCD8 levels and sIL-2R levels of the AML-CR patients showed a close correlation, p < 0.01. Further, the sCD8 levels and lymphokine activated killer cell cytotoxic activity showed a close correlation, p < 0.05. The presence of the activation of anti-tumor immunity may be related to the continuance of the remission in the AML-CR patients.
Adolescent↗
Increased soluble CD4 and decreased soluble CD8 molecules in patients with Sjögren's syndrome.
PURPOSE: A new enzyme-linked immunosorbent assay for soluble CD4 (sCD4) and soluble CD8 (sCD8) molecules has been developed. We estimated the concentrations of these molecules in patients with Sjögren's syndrome and in patients with systemic lupus erythematosus (SLE) serving as a control population for non-Sjögren's inflammatory disease, since several findings suggestive of an aberration of immunocompetent cells have been reported in these autoimmune diseases. PATIENTS AND METHODS: The study population consisted of 41 patients with Sjögren's syndrome (28 cases of the primary form and 13 cases of the secondary form), 66 patients with SLE, and 43 normal individuals. Serum samples and clinical and laboratory data were collected from each patient and control. Assays of the sCD4 and sCD8 molecules were performed using an enzyme-linked immunosorbent kit developed by T Cell Science Inc., Cambridge, MA. RESULTS: The concentration of sCD4 was significantly increased in patients with both primary and secondary Sjögren's syndrome as compared with that in the control subjects. In contrast, sCD8 was significantly decreased in patients with primary disease but not in patients with secondary disease. A low or high concentration of sCD8 was significantly correlated with the presence of anti-SS-A antibody or hypocomplementemia, respectively. A similar significant correlation was noted between an increased sCD4 concentration and increased serum IgG level. In patients with SLE, the levels of both sCD4 and sCD8 were significantly increased. CONCLUSION: These observations represent the first evidence of an increased level of the sCD4 molecule and a decreased level of the sCD8 molecule and an association with immunologic abnormalities in Sjögren's syndrome. The increased and decreased levels of these soluble molecules observed may play a pathologic role in patients with Sjögren's syndrome.
Adult↗
Identified diallyl polysulfides from an aged garlic extract which protects the membranes from lipid peroxidation.
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Animals↗
A survey of tardive dyskinesia in psychiatric inpatients in Japan.
To investigate the prevalence of tardive dyskinesia (TD) in a group of psychiatric patients receiving low doses of antipsychotic drugs, we examined 647 Japanese inpatients (361 men and 286 women) with a mean age of 49.8 years, receiving a mean dose of antipsychotic drugs of 276.8 mg of chlorpromazine equivalent. TD was diagnosed according to the criteria of Schooler and Kane with the Abnormal Involuntary Movement Scale. The overall prevalence of TD was 22.3%. Mild TD was found in 67.4% of TD patients, moderate TD in 29.2%, and severe TD in 3.5%. The TD patients were older (59.0 years) than those without this condition (47.2 years). The prevalence of TD increased with advancing age until the 7th decade, when it reached a plateau. The dose of daily antipsychotic drugs was lower in the TD patients (207.6 mg) than in the patients without TD (296.6 mg). The duration of primary illness was longer in the TD patients (28.9 years) than in the patients without TD (20.4 years). Patients receiving antiparkinsonism drugs showed TD less frequently (20.7%) than those not receiving such drugs (31.0%). No significant associations were found between the presence of TD and sex or primary illness.
Adolescent↗
Quantitative EEG of elderly schizophrenic patients.
To investigate the brain function of elderly schizophrenic patients, quantitative EEGs of such patients were compared with those of healthy elderly controls. In schizophrenics, increases in delta and slow theta (4.0-6.0 Hz) waves were thought to be due to the influence of antipsychotics. Characteristic EEG features of these patients included the following: 1) more fast theta (6.0-8.0 Hz) wave was observed, with less alpha wave faster than 9.0 Hz, 2) the reduction in alpha 3 (10.0-11.0 Hz) wave was limited to the frontal regions. The present EEG findings are thought to characterize the traits of the subtype of chronic severe schizophrenia. The reduction in alpha 3 wave in the frontal regions may be one expression of the hypofrontality of schizophrenia.
Age Factors↗
High molecular weight protein aggregates formed in the liver of the rat following large doses of paracetamol.
Paracetamol (200 and 500 mg kg-1) was given intraperitoneally to rats pretreated with 3-methylcholanthrene for 3 days. Glutamic oxalacetic acid transaminase (GOT) activity in plasma increased in rats receiving 500 mg kg-1 paracetamol. Plasma GOT activity was low at the dose of 200 mg kg-1, but the same dose to diethyl maleate pretreated rats increased the GOT activity. High mol. wt protein aggregates were found to be formed in liver homogenates and microsomes of rats which showed high plasma GOT activity, accompanied by depletion of hepatic glutathione. The formation of protein aggregates in the liver of rats following large doses of paracetamol suggests a contribution of lipid peroxidation to paracetamol-induced hepatotoxicity.
Acetaminophen↗
Species difference and tissue distribution of uridine diphosphate-glucuronyltransferase activities toward E6080, 1-naphthol and 4-hydroxybiphenyl.
The apparent in vitro kinetic constants of uridine diphosphate-glucuronyltransferase (UDP-GT) activities towards E6080, 1-naphthol (1-N) and 4-hydroxybiphenyl (4-HB) were determined using microsomes, to assess the effect of inducing agents and evaluate species and tissue differences. In rats, the 3-methylcholanthrene and beta-naphthoflavone treatments increased the Vmax app/KM app values for E6080, 13- and 8-fold, and those for 1-N, 1.9- and 1.7-fold, respectively, but did not affect those for 4-HB. Phenobarbital was ineffective on the UDP-GT activity toward E6080. In rats and rhesus monkeys, the intestinal mucosa had higher specific UDP-GT activity toward E6080 than did the liver, and the rank order of the Vmax app/KM app value for E6080 in the intestinal mucosa was rhesus monkey > rat > guinea pig > beagle. In guinea pig, the Vmax app/KM app value for E6080 in the liver was 4 times higher than that in the intestinal mucosa. Both the Vmax app/KM app values for 1-N and 4-HB in the liver of all species studied were higher than those in the intestinal mucosa, and guinea pig liver showed the highest values, while, about the Vmax app for 1-N and 4-HB, beagle liver had the highest values. In the beagle intestinal mucosa, the Vmax app/KM app values for all 3 substrates studied were extremely low.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Eucapnic hyperventilation-induced bronchoconstriction in rabbits.
We examined whether eucapnic hyperventilation with dry air produces the bronchoconstriction in anesthetized, non-sensitized rabbits and in ovalbumin sensitized rabbits. Eucapnic hyperventilation challenge with dry air containing 5% CO2 at room temperature was performed with 4 non-sensitized and 7 sensitized rabbits by mechanical ventilation for 15 min (120 breaths/min, 7 ml tidal volume/kg body weight). Total lung resistance (RL) and dynamic compliance (Cdyn) were measured before and 0, 5, 15, and 30 min after hyperventilation. In non-sensitized rabbits, RL and Cdyn did not change significantly. However, in sensitized rabbits, RL increased maximally by 48.9% +/- 9.0% at 5 min, and then decreased to the baseline level at 30 min after challenge. Cdyn decreased maximally by 12.5% +/- 3.5% at 15 min after challenge. These changes were significantly different from the baselines (p < 0.05). Furthermore, to investigate the role of histamine on hyperventilation-induced bronchoconstriction (HIB) in sensitized rabbits, we performed the hyperventilation challenges in 5 sensitized rabbits with the pretreatment of H1-receptor antagonist (chlorpheniramine, 1 mg/kg, i.v.) and found that the maximum increment of RL was suppressed to 24.2% +/- 7.4% of the control, which was significantly lower than the maximal RL in nontreated sensitized rabbits (p < 0.05). We concluded that HIB occurs only in sensitized rabbits and that histamine may play an important role in the development of HIB in sensitized rabbits.
Airway Resistance↗
Questionnaire surveys of cases of tick bite and Lyme borreliosis in hunters in Hokkaido with reference to detection of anti-Borrelia burgdorferi antibody.
An epidemic of Lyme borreliosis on Hokkaido island, Japan, was surveyed by questionnaire in 587 hunters. The 308 returns (52.4%) revealed episodes of tick bite (usually 2 or more) in 210 cases. Skin rashes appeared in 164 cases. Associated itching, pain, etc., but not skin rash, were more frequent after 2 or more tick bite. Previous determinations of anti-Borrelia burgdorferi antibody titers in these subjects and in controls suggested an association with outdoor activities other than hunting, and among 33 cases of dermatological symptoms and 23 of articular symptoms, 4 and 2, respectively, were antibody-positive. Most of these antibody-positive subjects had suffered tick bite at least twice, but had had no antibiotic treatment. Three subjects with joint disorders were antibody-positive. These findings suggested that the many hunters exposed to Borrelia burgdorferi frequently carried latent infections, and that some had latent form of arthritis, dermatitis and other disorders.
Adult↗
Microangiopathic hemolytic anemia in a graft-versus-host disease patient treated with cyclosporine A and prednisolone.
A 38-year-old male patient with chronic myelocytic leukemia in the first chronic phase underwent bone marrow transplantation (BMT) from an HLA identical sibling. He developed chronic graft-versus-host disease and his condition gradually deteriorated. Fourteen months after BMT, acute progressive anemia, thrombocytopenia, reticulocytosis, increased serum lactic dehydrogenase and increased serum bilirubin were revealed following treatment with cyclosporine A (240 mg/day i.v.), prednisolone (60 mg/day i.v.) and azathioprine (100 mg/day p.o.). Red blood cell fragmentations were also found microscopically. At that time, the serum cyclosporine A trough level was 1,300 ng/ml by the polyclonal antibody RIA method. These symptoms were resolved by discontinuation of cyclosporine A and administrations of aspirin, cilostazol, and dipyridamole as anti-platelet agents. We consider this phenomenon to be micro-angiopathic hemolytic anemia due to a serum high cyclosporine A level which resulted from the concomitant use of cyclosporine A with prednisolone.
Adult↗
Effects of famotidine on various immunological parameters in patients with rheumatic diseases: decreased lymphocyte DR expression by famotidine.
We examined the effect of famotidine, a histamine-type 2 receptor antagonist, on the immunocompetent cells. The number of DR(+) cells were significantly decreased in patients with systemic lupus erythematosus (P less than 0.05) by parenteral administration of famotidine (40 mg/days for 4 weeks). However, total lymphocyte number and monocyte number did not change. Immunoglobulin levels of patients with rheumatoid arthritis and normal male did not change. Furthermore, phytohemagglutinin induced lymphocyte proliferation was increased by addition of famotidine (10 ng/ml). Nonetheless, famotidine did not have mitogenic function itself to lymphocyte and did not affect IL-2 production.
Adjuvants, Immunologic↗
[Role of neutrophil and T cell functions in host defense mechanisms of the elderly].
We studied neutrophil functions (phagocytosis, intracellular killing and chemotaxis with or without recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and T cell functions (lymphocyte proliferation and production of GM-CSF in response to phytohemagglutin (PHA)) to clarify host defense mechanisms in the elderly. There was no significant difference in phagocytic activity of neutrophils between the elderly and control young adults. rhGM-CSF enhanced phagocytosis by neutrophils, and a similar degree of enhancement was obtained in both groups. Killing activity of neutrophils evaluated by the new Nitroblue tetrazolium reduction test in the elderly was significantly lower than that in young adults (p < 0.001), however, pretreatment of neutrophils with rhGM-CSF resulted in an increase of killing activity in the elderly, raising their response to a level comparable to that of young adults pretreated with rhGM-CSF. There was no significant difference between the elderly and young adults in chemotaxis of neutrophils. rhGM-CSF alone did not prime chemotaxis, but primed chemotaxis in response to chemoattractant (N-formyl-methionyl-leucyl-phenylalanin) in both individuals. Lymphocyte proliferation and production of GM-CSF in response to PHA in the elderly were significantly lower than those in the young adults (p < 0.001, p < 0.05, respectively). These results indicated that impaired T cell functions may contribute, at least in part, to susceptibility to bacterial infection in the elderly.
Aged↗