Biomedical subjects

T Hada

Publications and source records attributed to T Hada.

At least 19 recordsLinked to original sources

PubMed2005

Immunomodulatory effects of selective leucocytapheresis as a new adjunct to interferon-alpha2b plus ribavirin combination therapy: a prospective study in patients with high plasma HCV viraemia.

Efficacy of interferon-alpha2b (IFN) + ribavirin (IFN/RBV) combination in patients with high plasma hepatitis C virus (HCV) is very poor. Dysregulated CD4+ /CD8+ T cells is involved in both impaired cell-mediated immunity and resistance to IFN. Adsorptive granulocytes and monocytes apheresis (GMA) can remove infected leucocytes which are extrahepatic HCV reservoirs and also has been associated with intriguing immunomodulation and increases in CD4+ T cells. Our aim was to see if GMA enhances the efficacy of IFN/RBV. Twenty-four patients, 13 IFN resistant and 11 IFN naive were enrolled. Seventeen were genotype 1b and 7 were 2a or 2b. Mean plasma HCV-RNA was 612.9 (100-850) kIU/mL and alanine aminotransferase, 108 (41-373) U/L. GMA was performed with Adacolumn at one session/day for five consecutive days and IFN/RBV was started within 24 h after the last GMA session. Daily 6 million units of IFN, six times/week for 2 weeks and then three times/week for 22 weeks were given with RBV (600-800 mg/day/patient). Patients were followed for 6 months. GMA was associated with a significant increase in lymphocyte counts, complement activation fragment C3a and falls in tissue necrosis factor-alpha, and IL-8 produced by peripheral blood leucocytes. At week 24, 20 of 24 patients (83%) were HCV negative and by end of follow-up (week 49), the remission was sustained in 14 of 24 patients (58%) including 100% of patients with 2a or 2b. In conclusion, enhanced efficacy of IFN/RBV following GMA might be attributed to a more efficient immune function and a renewed IFN signaling towards HCV.

Adjuvants, Immunologic↗

PubMed2004

Effect of purine-free low-malt liquor (happo-shu) on the plasma concentrations and urinary excretion of purine bases and uridine--comparison between purine-free and regular happo-shu.

To determine whether purine-free and regular low-malt liquor beverages (happo-shu) increase the plasma concentration and urinary excretion of purine bases (hypoxanthine, xanthine, uric acid) and uridine, 6 healthy males were given regular (10 ml/kg of body weight) and purine-free happo-shu (10 ml/kg of body weight). Plasma concentration-time curves were plotted, and the areas under the curves for uric acid and total purine bases (the sum of hypoxanthine, xanthine, and uric acid) were greater in the regular than in the purine-free happo-shu ingestion experiment (both p < 0.05). In addition, the total urinary excretion of xanthine, total purine bases, and uridine was greater in the regular than in the purine-free happo-shu ingestion experiment (p < 0.05 in all cases), although the total urinary excretion of hypoxanthine and uric acid was no different between the regular and the purine-free happo-shu ingestion experiments. These results suggest that uridine contained in regular happo-shu might contribute to an increase in the urinary excretion of uridine along with ethanol, and that the purines contained in regular happo-shu may contribute to the increase in plasma concentration of uric acid due to purine degradation.

Adult↗

PubMed2003

Parametric instabilities of circularly polarized Alfvén waves in a relativistic electron-positron plasma.

Dispersion relation and nonlinear evolution of the parametric instabilities of circularly polarized Alfvén waves in a relativistic electron-positron plasma are investigated by theoretical and numerical approaches. In the nonrelativistic limit, when 2omega(2)(p)>omega20, the characteristics of the instabilities are similar to those in an electron-ion plasma, except that the modulational instability takes place only if v(2)(s)<omega(2)(0)/k(2)(0), where omega(p) and v(s) denote the plasma frequency and the acoustic speed, and omega(0), k(0) indicate the frequency and the wave number of the parent wave. On the other hand, when 2omega(2)(p)<omega20, two new types of instabilities emerge between the parallel or antiparallel propagating Alfvén-like waves and the parallel propagating Langmuir-like wave. The weakly relativistic effect is discussed for all the instabilities. The one-dimensional full particle simulation and bicoherence analysis of the simulation result suggest that successive decay via the interaction between the parallel propagating Langmuir-like wave and antiparallel propagating Alfvén-like wave can efficiently generate a continuum of low frequency electromagnetic waves, which can interact with energetic particles.

Journal Article↗

PubMed2003

Effects of novelty stress on neuroendocrine activities and running performance in thoroughbred horses.

This study investigated the effects of novelty stress on neuroendocrine activities and running performance in Thoroughbred horses. First, to examine the neuroendocrine responses to novelty stress, we exposed horses to two types of novel environmental stimuli (audiovisual or novel field stimuli). After the stimuli, plasma concentrations of vasopressin, catecholamines and adrenocorticotropin (ACTH), as well as heart rates, were significantly increased in each experiment. Second, we investigated neuroendocrine activities during incremental exercise. Plasma concentrations of vasopressin, catecholamines, ACTH and blood lactate increased as the exercise load increased. Finally, we investigated the effects of novelty stimuli on neuroendocrine activities and running performance during supra-maximal exercise (110% VHRmax). When the novelty stimuli were presented to horses, the increases in plasma vasopressin and catecholamines due to exercise load were significantly smaller than those in the control experiments. Blood lactate during supra-maximal exercise was also significantly lower and total run time until exhaustion was prolonged in the novel environmental stimuli compared to the control. These results suggest that novelty stimuli facilitate vasopressin release from the posterior pituitary in addition to activating the sympatho-adrenomedullary and the hypothalamic-pituitary-adrenocortical axes in thoroughbred horses, and increase exercise capacity, resulting in improvement of running performance during supra-maximal exercise.

Adrenocorticotropic Hormone↗

PubMed2002

Biomechanical implications of uphill training on the aetiology of tendinitis.

It has been reported that a small decrease in the strain in the superficial digital flexor tendon (SDFT) occurs if the toe is raised during walking. Although walking on a slope appears similar to raising the toe, it is unclear whether uphill exercise decreases the strain in the SDFT. Because the force or strain on tendons is one of the important factors leading to tendon stress injury, we hypothesised that reducing the force in the SDFT during exercise may prevent tendinitis. The purpose of this study was to determine the effects of treadmill inclination on the force in the SDFT in the walking horse. 'Arthroscopically implantable force probes' (AIFP) were implanted into the SDFT of the forelimb of 4 horses. The AIFP output was recorded during walking on a treadmill inclined at 0%, 3%, 8% and then 0% again. When the inclination increased from 0 to 8%, the first peak of force in the SDFT decreased significantly, the second increased significantly, but the maximal force and the area under the force-time curve did not change. In conclusion, uphill walking on an inclined treadmill did not decrease the maximal force in the SDFT or the area under the force-time curve, however, the patterns of force were altered. Future research should focus on the force distributions of tendons and ligaments at faster gaits, because the effects of a change in hoof angle and slope may be greater at faster gaits.

Animals↗

PubMed2001

Fas ligand-induced caspase-1-dependent accumulation of interleukin-18 in mice with acute graft-versus-host disease.

Acute graft-versus-host disease (aGVHD), the fatal side effects of bone marrow transplantation, was shown to be accompanied by elevation of serum levels of interleukin 18 (IL-18). In this study, the mechanism underlying the accumulation of IL-18 in aGVHD in mice was investigated. Lethally irradiated recipients having transplantation with H-2 disparate donor splenocytes demonstrated aGVHD and contained markedly elevated serum levels of IL-18. In contrast, recipients having transplantation with gld/gld spleen cells, which lack functional Fas ligand (FasL), contained only normal ranges of IL-18, indicating FasL-mediated IL-18 release in aGVHD. The wild-type hosts engrafted with caspase-1-deficient cells revealed marked increases of IL-18 similar to those engrafted with wild-type cells, whereas caspase-1-deficient recipients engrafted with wild-type cells showed only a slight elevation of serum IL-18, indicating that IL-18 elevation is derived from host cells in a caspase-1-dependent manner. These results suggest FasL-mediated caspase-1-dependent IL-18 secretion in aGVHD in mice.

Acute Disease↗

PubMed2001

Functioning adrenal black adenoma with pulmonary and cutaneous cryptococcosis: a case report and review of English literature.

A 53-year-old woman experienced progressive general weakness and lumbago in the 2 years prior to a physical examination which disclosed cushingoid manifestations and a skin ulcer on the back of her right knee joint. Her plasma cortisol concentration ranged from 24.7 to 31.1 microg/dl, with an ACTH level <5 pg/ml. Urinary excretions of 17-hydroxycorticosteroid (17-OHCS) and 17-ketosteroid (17-KS) were 20.5 mg/day and 5.1 mg/day, respectively, and urinary cortisol was also increased (421 microg/day). Cortisol was not suppressed after the administration of 8 mg dexamethasone. Abdominal ultrasound sonography, computed tomography (CT) scan, and magnetic resonance imaging (MRI) studies demonstrated a left adrenal tumor and further, a chest X-ray examination showed a cavitary lesion containing a fungus ball-like mass in the left lower lung field. The serum cryptococcal antigen titer was positive at 1:128 and a bronchoalveolar lavage fluid culture yielded a growth of Cryptococcus neoformans. A biopsy specimen of the skin ulcer also suggested cryptococcosis. As a result, a left adrenectomy was performed, and the excised specimen was shown to be an adenoma consisting of compact cells with abundant pigmentation (black adenoma). A diagnosis of functioning black adenoma of the adrenal gland, complicated with pulmonary and cutaneous cryptococcosis was made.

Adrenal Gland Neoplasms↗

PubMed2001

Identification of a new point mutation in the human xanthine dehydrogenase gene responsible for a case of classical type I xanthinuria.

A 60-year-old Japanese man was diagnosed as having hypouricemia at an annual health check-up. The routine laboratory data was not remarkable except that the patient's hypouricemia and plasma levels of xanthine and hypoxanthine were much higher than those of normal subjects. Furthermore, the patient's daily urinary excretion of xanthine and hypoxanthine was markedly increased compared with reference values. The xanthine dehyrogenase activity of the duodenal mucosa was below the limits of detection. Nevertheless, allopurinol was metabolized to oxypurinol in vivo. Based on these findings, a subtype of classical xanthinuria (type I) was diagnosed. The xanthine dehyrogenase protein was detected by Western blotting analysis. Sequencing of the cDNA of the xanthine dehyrogenase obtained from the duodenal mucosa revealed that a point mutation of C to T had occurred in nucleotide 445. This changed codon 149 from CGC (Arg) to TGC (Cys), a finding that has not been previously reported in patients with classical xanthinuria type I.

Allopurinol↗

PubMed2001

An atypical case of primary renal tubular hypokalaemic metabolic alkalosis with chronic tophaceous gout.

A 55-year-old woman was referred to our ward for further evaluation of marked hyperuricaemia and suspected tophi. On physical examination, huge subcutaneous nodules were observed on the knee joints as well as a small nodule on the lateral side of the left sole. Blood chemistry showed marked hyperuricaemia (0.85 mmol/l), hypokalaemia (2.7 mmol/l) and a mild degree of renal insufficiency. Arterial blood gas analysis showed signs of metabolic alkalosis. Daily urinary uric acid excretion on a purine non-restricted diet was 8.9 mmol/day. Uric acid clearance and fractional uric acid clearance were 0.8 ml/min and 2.6%, respectively. Plasma renin activity was 21.8 ng/ml/h, and plasma angiotensin II and aldosterone concentrations were 61 and 121 pg/ml, respectively. However, pressor response to an intravenous administration of angiotensin II was normal. The urinary calcium to creatinine molar ratio was 0.069, and serum magnesium concentration was normal to supranormal. A biopsy of the subcutaneous nodule showed a typical appearance of tophus. Based on these findings, the patient was diagnosed with an atypical case of renal tubular hypokalaemic metabolic alkalosis, with marked hyperuricaemia and tophi as the initial manifestations. So far, only four cases of Bartter's syndrome with gout and/or hyperuricaemia have been described in Japan. This rare case is presented and its mechanism of hyperuricaemia discussed.

Arthritis, Gouty↗

PubMed2001

Human xanthine dehydrogenase cDNA sequence and protein in an atypical case of type I xanthinuria in comparison with normal subjects.

To investigate the properties of xanthine dehydrogenase/xanthine oxidase (XDH/XO) deficiency in a patient with atypical type I xanthinuria, as indicated by oxypurine data, a cDNA sequence encoding XDH, XDH/XO immunoblot analysis and a competitive PCR assay were performed, and the results were compared with those of normal subjects. The xanthine dehydrogenase cDNA sequence of the patient was consistent with the controls, while immunologically reactive 150 kD XDH/XO protein was not present in the xanthinuric duodenal mucosa, unlike the control duodenal mucosa. In addition, a decrease in XDH/XO messenger RNA was found by competitive PCR. These results suggest that atypical type I xanthinuria is due to a decrease in messenger RNA of XDH/XO. Furthermore, it was considered that this decrease could explain the normal plasma level and near normal urinary excretion of hypoxanthine seen in this case of xanthinuria, though XDH/XO activity and protein were not detected spectrophotometrically and immunologically, respectively.

Base Sequence↗

PubMed2001

Effect of furosemide on renal excretion of oxypurinol and purine bases.

To examine whether furosemide affects the plasma concentration and urinary excretion of purine bases and oxypurinol, we administered allopurinol (300 mg) orally to 6 healthy subjects and then administered furosemide (20 mg) intravenously 10 hours later. Furosemide (20 mg) decreased the urinary excretion of uric acid by 40% (P < .01), oxypurinol by 39% (P < .05), and xanthine by 43% (P < .05) and the fractional clearance of uric acid by 45% (P < .01) and oxypurinol by 34% (P < .05) when measured 1 to 2 hours after administration. Moreover, furosemide increased the plasma concentration of uric acid by 6% at 1.5 hours after administration. These results indicate that furosemide may decrease the urinary excretion of uric acid and oxypurinol by acting on their common renal transport pathway(s). In addition, it is suggested that the effect of furosemide on oxypurinol is clinically important, since the hypouricemic effect of allopurinol may become more potent as a result.

Administration, Oral↗

PubMed2001

Increased visceral fat accumulation further aggravates the risks of insulin resistance in gout.

We performed the present study to determine the degree of visceral fat accumulation and incidence of visceral fat obesity in 138 gout patients who were classified as overexcretion type (n = 53) and underexcretion type (n = 85) by their levels of uric acid clearance and urinary uric acid excretion. We also investigated the relationship between visceral fat accumulation and insulin resistance expressed by the homeostasis model assessment (HOMA) index. Visceral fat area (VFA)/surface body area (SBA) was significantly increased in patients with gout as compared with control subjects (79.7 +/- 30.8 cm(2)/m(2) v 65.1 +/- 24.1 cm(2)/m(2), P <.001). It was also shown that VFA/SBA in the gout overexcretion group was significantly increased as compared with the gout underexcretion group (88.3 +/- 32.8 cm(2)/m(2) v 74.3 +/- 28.3 cm(2)/m(2), P <.01). Although the incidence of visceral fat obesity (VFO) was not different between gout patients and control subjects, the incidence of VFO was significantly higher in the gout overexcretion type than the gout underexcretion type (19 of 53 v 11 of 85, P <.01). Further, there was a significant relationship between visceral fat area and HOMA index. Gout patients possess some factors that are included in the insulin resistance syndrome, irrespective of the presence of VFO, and the insulin resistance risk factors observed in gout become more prominent when it is complicated with VFO. Our results suggest that gout patients, especially the overexcretion type who have greater levels of visceral fat accumulation, may be more vulnerable to atherosclerotic diseases.

Adult↗

PubMed2001

Decreased activities of lipoprotein lipase and hepatic triglyceride lipase in patients with gout.

Postheparin plasma lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities were measured in 30 male primary gout patients as well as in control subjects. The activities of these lipolytic enzymes were significantly decreased in the patients as compared with the controls (gout v control; LPL, 5.4 +/- 0.4 v 7.9 +/- 0.9 U; HTGL, 14.6 +/- 2.0 v 17.9 +/- 3.4 U) when matched with serum triglyceride concentration. Further, LPL activity was negatively correlated with serum- and very-low-density lipoprotein (VLDL)-triglyceride in gout patients, while that of HTGL was negatively correlated with low-density lipoprotein (LDL)-triglyceride in both gout patients and control subjects. These results suggest that decreased activities of LPL and HTGL may contribute, in part, to the increased concentrations of serum-, VLDL-, and LDL-triglyceride seen in gout patients, leading to a higher risk for coronary atherosclerotic diseases in gout.

Adult↗

PubMed2001

Effect of norepinephrine on the urinary excretion of purine bases and oxypurinol.

To examine whether norepinephrine affects the plasma concentrations and urinary excretion of purine bases and oxypurinol, we orally administered allopurinol (300 mg) to 5 healthy subjects and 9 hours later intravenously administered norepinephrine (12 to 20 microg/kg body weight), which causes a more than 10 mm Hg increase in diastolic pressure for 2 hours. Norepinephrine decreased the urinary excretion of uric acid by 33% (P <.01), oxypurinol by 32% (P <.01), and xanthine by 51% (P <.01), as well as the fractional clearance of uric acid by 32% (P <.01), oxypurinol by 24% (P <.05), and xanthine by 21% (P <.05) when measured 1 to 2 hours after administration. These results indicate that norepinephrine decreases the urinary excretion of uric acid, oxypurinol, and xanthine, probably via hemodynamic change. It is also suggested that the hypouricemic effect of allopurinol may be more potent than that expected in gout patients with enhanced sympathetic tone, such as in salt-sensitive hypertension.

Adult↗

PubMed2001

Widespread cellular distribution of aldehyde oxidase in human tissues found by immunohistochemistry staining.

Aldehyde oxidase (EC 1.2.3.1) is a xenobiotic metabolizing enzyme that catalyzes a variety of organic aldehydes and N-heterocyclic compounds. However, its precise pathophysiological function in humans, other than its xenobiotic metabolism, remains unknown. In order to gain a better understanding of the role of this enzyme, it is important to know its exact localization in human tissues. In this study, we investigated the distribution of aldehyde oxidase at the cellular level in a variety of human tissues by immunohistochemistry. The enzyme was found to be widespread in respiratory, digestive, urogenital, and endocrine tissues, though we also observed a cell-specific localization in the various tissues studied. In the respiratory system, it was particularly abundant in epithelial cells from the trachea and bronchium, as well as alveolar cells. In the digestive system, aldehyde oxidase was observed in surface epithelia of the small and large intestines, in addition to hepatic cells. Furthermore, the proximal, distal, and collecting tubules of the kidney were immunostained with various intensities, while glomerulus tissues were not. In epididymus and prostate tissues, staining was observed in the ductuli epididymidis and glandular epithelia. Moreover, the adrenal gland, cortex, and notably the zona reticularis, showed strong immunostaining. This prevalent tissue distribution of aldehyde oxidase in humans suggests some additional pathophysiological functions besides xenobiotic metabolism. Accordingly, some possible roles are discussed.

Aldehyde Oxidase↗

PubMed2001

Basedow's disease and chronic ulcerative colitis: a case report and review of the Japanese literature.

A case of Basedow's disease, that developed after successful treatment of ulcerative colitis with a total colectomy, is presented, along with a review of the Japanese literature on the coexistence of hyperthyroidism and ulcerative colitis. A 26-year-old man was referred to our department, complaining of general fatigue, appetite loss, and palpitation. At age 14, blood was discovered in his stool and a diagnosis of ulcerative colitis was made. Since then, he has been treated with salazosulfapyridine and prednisolone. On examination, mild exophthalmos and thyroid swelling were observed. Both serum free T3 and T4 levels were increased along with a positive TSH receptor antibody, while TSH was decreased. Scintigraphic and ultrasonographic examinations of the thyroid gland showed diffuse enlargement. Treatment with thiamazole relieved the symptoms and normalized the thyroid function. Although a high incidence of autoimmune thyroid diseases in association with ulcerative colitis has been suggested, only 6 cases of hyperthyroidism coexisting with ulcerative colitis have been reported in Japan. A common immunological process has been suggested to be implicated in the pathogenesis of this association, however, the exact mechanism remains unclear.

Adult↗

PubMed2001

Idiopathic hemochromatosis with the mutation of Ala176Val heterozygous for HFE gene.

Most patients with hereditary hemochromatosis are homozygous for C282Y in the HFE gene in populations of Celtic origin, but the genetic cause of this disease is unknown in Japan because of its rarity. A 48-year-old Japanese patient was recently diagnosed with idiopathic hemochromatosis. Analysis of the entire coding region of the patient's HFE by RT-PCR showed a heterozygous nucleotide substitution at nucleotide 527 from C to T, which resulted in A176V amino acid substitution. Another mutation at nucleotide 942 from T to C was observed, but this was a nonsense mutation. C282Y and another mutation, H63D, were not found in the patient. The mutation may have a possible role on the cause of hemochromatosis in this Japanese case.

Alanine↗

PubMed2001

Spontaneous regression of hepatic adenoma in a patient with glycogen storage disease type I after hemodialysis: ultrasonographic and CT findings.

A 23-year-old woman was admitted to our hospital with recurrent gouty arthritis. Laboratory findings showed hypoglycemia, lactic acidosis, hyperlipidemia, and hyperuricemia, with normal values of serum alfa-fetoprotein (AFP) and protein induced by vitamin K absence (PIVKA-II). A diagnosis of glycogen storage disease type I (GSD-type I) was made on the basis of the laboratory data, liver biopsy findings, and partially deficient thrombocyte glucose-6-phosphatase (G-6-Pase) activity. Ultrasonography and computed tomography revealed multiple focal hepatic masses. Biopsied specimens of the lesion demonstrated a hepatic adenoma, which changed in appearance in the relatively short period between echography and computed tomography. This interesting phenomenon may highlight the importance for careful follow-up of hepatic adenomas, because of the potential of rupture, hemorrhage, or malignant transformation. During follow-up, the present patient received hemodialysis due to renal failure, and the adenoma regressed spontaneously after 8 years. Included are diagnostic images, demonstrating the association of hepatic adenoma and GSD-type I.

Adenoma, Liver Cell↗