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Biomedical subjects

K Hirota

Publications and source records attributed to K Hirota.

At least 199 records · Page 11Linked to original sources

GRO-alpha in human serum: differences related to age and sex.

PROBLEM: Human GRO-alpha (GRO-alpha) is a new member of the chemokine family that is supposed to play an important role in inflammatory and immune reactions. We established a sandwich enzyme-linked immunoassay (ELISA) system with polyclonal antibodies against human GRO-alpha and investigated the serum level of healthy donors to establish normal ranges for this chemokine in adults. METHODS: GRO-alpha concentrations were measured cross-sectionally in the sera of 240 healthy adults. The variability of serum GRO-alpha levels was also measured in normal volunteers, samples from whom were obtained by sequential venipunctures or by a small plastic cannula with a heparin-saline lock, to determine short-term variability. RESULTS: Whereas there was no difference between the concentration of human GRO-alpha from men (logarithmic mean, 77.6 pg/ml, n = 120) and that from women with normal menstrual cycles (log mean, 71.6 pg/ml, n = 73), the concentration from postmenopausal women (log mean 45.0 pg/ml, n = 31) was lower than that from women with normal menstrual cycles (log mean 71.6 pg/ml, n = 73). However, we could not detect any significant difference between healthy donors' serum levels and those of donors with acute inflammation. Fewer variations were recognized in the case of the sequential venipunctures method than in that of the heparin-saline lock method. CONCLUSION: We found that the GRO-alpha concentration of postmenopausal women was significantly lower than that of women with normal menstrual cycles. These results suggest the GRO-alpha serum levels of normal healthy women may have some correlation with sex hormones.

Acute Disease↗

High prevalence of cytotoxin positive Helicobacter pylori in patients unrelated to the presence of peptic ulcers in Japan.

BACKGROUND: It has been reported that infection with vacuolating cytotoxin positive Helicobacter pylori strains is associated with gastroduodenal disease in Western countries. AIMS: To evaluate the prevalence of cytotoxin producing strains among patients with H pylori infection in relation to gastrointestinal diseases in Japan. PATIENTS: Ninety seven patients undergoing endoscopy. METHODS: A Western blot assay was conducted to detect serum antibodies against the cytotoxin using recombinant cytotoxin (VacA protein) as an antigen. To obtain a purified recombinant cytotoxin, the vacA gene (2233 nucleotides) was cloned into an expression vector to produce the protein (744 amino acids), which was expressed in Escherichia coli. RESULTS: Serum IgG antibodies to the cytotoxin were present in 85%, 95%, 95%, and 100% of infected patients with gastric ulcer (n = 26), duodenal ulcer (n = 21), chronic gastritis (n = 19), and endoscopically normal mucosa (n = 14), respectively. CONCLUSION: The western blot method using recombinant VacA protein is simple and useful for detecting antibody to vacuolating cytotoxin. This method showed antibodies against cytotoxin were highly prevalent, even in subjects with endoscopically normal mucosa in Japan, indicating that the cytotoxin may not be an independent cause of gastrointestinal diseases induced by H pylori infection.

Amino Acid Sequence↗

Atrophy of the cerebellum and brainstem in dentatorubral pallidoluysian atrophy. Influence of CAG repeat size on MRI findings.

To elucidate how the size of the expanded CAG repeat of the gene for dentatorubral pallidoluysian atrophy (DRPLA) and other factors affect the atrophy of the brainstem and cerebellum, and the appearance of high-intensity signals on T2-weighted MRI of the cerebral white matter of patients with DRPLA, we quantitatively analyzed the MRI findings of 26 patients with DRPLA, the diagnosis of which was confirmed by molecular analysis of the DRPLA gene. When we classified the patients into two groups based on the size of the expanded CAG repeat of the DRPLA gene (group 1, number of CAG repeat units > or = 66; group 2, number of CAG repeat units < or = 65), we found strong inverse correlations between the age at MRI and the areas of midsagittal structures of the cerebellum and brainstem in group 1 but not in group 2. Multiple regression analysis, however, revealed that both the patient's age at MRI and the size of the expanded CAG repeat correlated with the areas of midsagittal structures. Involvement of the cerebral white matter as detected on T2-weighted images was observed more frequently in patients belonging to group 2 than in group 1 patients. Furthermore it was demonstrated that high-intensity signals can be detected on T2-weighted images of the cerebral white matter of patients with a largely expanded CAG repeat (group 1) in their thirties. These results suggest that patient age as well as the size of the expanded CAG repeat are related to the degree of atrophy of the brainstem and cerebellum, and the white matter changes in patients with DRPLA.

Adolescent↗

[Treatment of gingivitis in elderly patients in a nursing home].

For 3 months, 4 patients in a nursing home for the elderly received supervised professional oral care in conjunction with oral hygiene instruction. Within the first month after the start of this program, plaque was reduced to 1/3 and gingivitis was reduced to 1/9 of their respective initial levels. In 5 patients who did not receive either oral hygiene instruction or professional oral care, plaque retention and gingivitis were unchanged. We conclude that professional oral care combined with oral hygiene instruction supervised by dental professionals can help to control gingivitis in the elderly.

Aged↗

[Pharyngeal bacteria and professional oral health care in elderly people].

In 15 elderly residents of an old-age home, we measured the total number of bacteria and the numbers of streptococci and staphylococci in the pharynx over 5 months. Seven residents received professional oral health care from dentists and dental hygienists and eight practiced oral care by themselves or together with a helper. During the 5 months, the total number of bacteria and the numbers of streptococci and staphylococci decreased (p < 0.01) in those who received professional care. In contrast, the total number of bacteria and the numbers of streptococci and staphylococci neither did not change or increased in those who did not receive professional care. These findings show that professional oral health care by dentists and dental hygienists can decrease the total number of bacteria and the numbers of streptococci and staphylococci in the pharynx of elderly people, which might prevent aspiration pneumonia.

Aged↗

[Anesthetic management of a pediatric patient with non-Fukuyama type congenital muscular dystrophy].

Non-Fukuyama type congenital muscular dystrophy (n-FCMD), a subtype of progressive muscular dystrophy (PMD), is a very rare autosomal recessive disorder. N-FCMD is characterized by severe and progressive motor weakness and atrophies of proximal muscles during the infant period. A 9-year-old boy with n-FCMD underwent elective surgery for muscle release around the hip joints bilaterally. As many perioperative complications related with volatile anesthetics and muscle relaxants had been reported in the anesthetic management of PMD, these drugs were thought to be contraindicated in patients with n-FCMD. Because n-FCMD seemed to have very similar pathogenesis with PMD, caudal epidural block was chosen, supplemented with the administration of diazepam, pentazocine and nitrous oxide. The operation and anesthesia were conducted uneventfully. No complications occurred postoperatively.

Adjuvants, Anesthesia↗

[Diffuse alveolar hemorrhage associated with idiopathic interstitial pneumonia syndrome after allogeneic bone marrow transplantation].

A 24-year-old male with myelodysplastic syndrome (refractory anemia) was treated with allogeneic bone marrow transplantation (BMT) from HLA-identical brother on September 9, 1994, after conditioning with busulfan and cyclophosphamide. From early in April 1995, the patient complained of cough and fever. Chest X-ray showed interstitial infiltrates involving hilar and lower lung fields. Although pulmonary infiltrates were resolved with methylprednisolone pulse therapy, on May 19, the patient rapidly deteriorated with dyspnea. Diffuse alveolar infiltrates appeared on chest X-ray and he died of respiratory failure. At autopsy, diffuse alveolar hemorrhage accompanied with thickening of the alveolar walls and interstitial infiltration of lymphocytes was demonstrated. There was no evidence of bleeding in other organs. This is a rare case of diffuse alveolar hemorrhage in the late stage of allogeneic BMT. This report should lead to an evaluation of this disease by the collection of similar cases.

Adult↗

Induction and nuclear translocation of thioredoxin by oxidative damage in the mouse kidney: independence of tubular necrosis and sulfhydryl depletion.

Adult T-cell leukemia-derived factor (ADF), originally defined as an interleukin-2 receptor inducer, is a human thioredoxin (TRX). ADF/TRX is a conserved multifunctional reductant presumably associated with redox regulation of the cellular environment; it works in vitro as a cytokine, free radical scavenger, activator of transcription factors, and substrate for several enzymes. In the present series of experiments, we studied the expression and intracellular localization of ADF/TRX in mouse kidney from two different renal tubular injury models: a free radical-associated model with ferric nitrilotriacetate (Fe-NTA) and a free radical-independent model with HgCl2. Markers of oxidative damage, such as 8-hydroxy-2'-deoxyguanosine, thiobarbituric acid-reactive substances, and 4-hydroxy-2-nonenal-modified proteins, were significantly increased in kidney from male C57B/6 mice 1 hour after a single intraperitoneal injection of Fe-NTA (5 mg iron/kg). However, in kidney from mice given a subcutaneous injection of HgCl2 (5 mg Hg/kg), none of these markers were increased, despite tubular necrosis with sulfhydryl depletion. In the Fe-NTA model only, Northern and Western blot analyses of the kidney revealed induction of ADF/TRX (> 2.5-fold) after 16 hours and translocation of ADF/TRX from the cytoplasmic to nuclear fraction (> 3.5-fold) after 24 hours. Immunohistochemistry showed a patchy distribution of ADF/TRX in the normal renal proximal tubules. In ex vivo experiments using serial normal kidney frozen sections, it was found that renal proximal tubules with low expression of ADF/TRX were more vulnerable to oxidative stress mediated by Fe-NTA. Collectively, these data suggest that: (a) ADF/TRX is induced and translocated to nuclei by oxidative damage mediated by Fe-NTA in the renal proximal tubules; (b) induction of ADF/TRX is independent of tubular necrosis or sulfhydryl depletion; and (c) ADF/TRX is involved in the cellular defense mechanisms in vivo against oxidative damage.

8-Hydroxy-2'-Deoxyguanosine↗

[Adult onset Still's disease with a brainstem lesion demonstrated on MRI].

We report a 39-year-old man with seven-year history of adult onset Still's disease (AOSD) who developed left abducens palsy and ataxic gait. T2-weighted MRI demonstrated high-intensities in the left side of the lower pons, including nucleus abducens and the inferior cerebellar peduncle, and in the right anteromedial portion of the thalamus corresponding to his neurological abnormalities. He responded favorably to corticosteroid treatment, and the high-intensities in the T2-weighted MRI diminished subsequently. Previously, he had developed bilateral sensorineural hearing loss which had responded to corticosteroid treatment during an exacerbation of the disease. There was no evidence of multiple sclerosis or other systemic diseases affecting the central nervous system (CNS) in the laboratory findings. Although the precise reason for the MRI lesions was unclear, we thought they were CNS manifestations of Still's disease. We suggest that AOSD is one of the causes of focal CNS involvement in young adults, particularly who has a history of fever of unknown origin.

Abducens Nerve↗

[Influence of fluid replacement on serum magnesium concentration and proper magnesium supplementation during general anesthesia].

We have studied the influence of fluid replacement on serum magnesium (Mg2+) concentrations, and studied proper Mg2+ supplementation during general anesthesia. Thirty eight patients undergoing elective surgery randomly received: Mg(2+)-free acetated Ringer solution (Group I, n = 15), acetated Ringer solution containing 0.5 mmol.l-1 of Mg2+ (Group II, n = 6), 1.0 mmol.l-1 of Mg2+ (Group III, n = 7), 2.0 mmol.l-1 of Mg2+ (Group IV, n = 6), or 4.0 mmol.l-1 of Mg2+ (Group V, n = 4). Measurements were made on serum and urine Mg2+ concentrations during anesthesia. In Group I, the serum Mg2+ concentrations decreased in correspondence with the water balance. It is suggested that dilution due to the fluid replacement induced the reduction in serum Mg2+ concentrations since the observed urine Mg2+ concentrations were negligible. In Group II-V, the reduction in serum Mg2+ concentrations was inhibited by Mg2+ supplementation, and the serum Mg2+ concentrations remained unchanged in Group IV. We conclude the Mg2+ supplementation is required during anesthesia when a large amount of fluid is infused.

Adolescent↗

[Changes in epidural pressure during total intravenous anesthesia with propofol, fentanyl and ketamine].

Although ketamine elevates cerebrospinal fluid pressure (CSFP) with an increase in cerebral blood flow, sedatives such as benzodiazepines, barbiturates and opioids have been reported to inhibit it. In this study, we evaluated the changes in epidural pressure (EP) as a good index for CSFP during total intravenous anesthesia with propofol-fentanyl-ketamine (PFK) compared to isofluranenitrous oxide anesthesia (GOI). Twelve patients for gastrectomy were allocated to two groups: PFK (n = 6) and GOI group (n = 6). In PFK group, epidural pressure did not increase during the anesthesia, and was significantly lower than in GOI group (30 and 180 min after induction of anesthesia, and 0, 30 and 60 min after stopping anesthetic administration). The present data suggest that PFK may safely be used for patients with intracranial hypertension.

Aged↗

[Rhabdomyolysis following water intoxication in two schizophrenic patients].

We report two cases of self-induced water intoxication with rhabdomyolysis. They had been diagnosed as chronic schizophrenia, and admitted to mental hospitals. The patients were transferred to our emergency room because of sudden loss of consciousness and generalized convulsions. Laboratory findings revealed marked hyponatremia (case 1; 109 mEq/L and case 2; 104 mEq/L). CT scans showed the effacement of interhemispheric and bilateral sylvian fissures and sulci of the cerebral hemisphere due to diffuse brain edema. 10% glycerol and saline were intravenously injected to the patients. They recovered from hyponatremia after excreting a large amount of urine. Their disturbed consciousness recovered to the normal level in parallel with the normalization of their serum sodium concentration. Soon after the normalization of their consciousness level, their serum creatine kinase (CK) was markedly elevated (case 1; 13086 IU/L and case 2; 41832 IU/L), and their serum myoglobin level was also significantly elevated (case 1; 2670 ng/ml and case 2; 1420 ng/ml). A sufficient amount of transfusion was performed for avoiding the acute renal failure. The two patients recovered from rhabdomyolysis without any severe complication. We conclude that brain CT is useful for the diagnosis of brain edema, and monitoring of CK is also important to anticipate renal damage secondary to rhabdomyolysis.

Adult↗

Synthesis of 6-aminouracils and pyrrolo[2,3-d]pyrimidine-2,4-diones and their inhibitory effect on thymidine phosphorylase.

Inhibitors of thymidine phosphorylase (dThdPase) are expected to suppress the growth and metastasis of tumor cells by inhibition of angiogenesis and were designed by utilizing the three dimensional structure of the enzyme. 5-Substituted 6-aminouracils (5) and 7-substituted pyrrolo[2,3-d]pyrimidine-2,4-diones (6) were synthesized and tested for inhibition of human placenta thymidine phosphorylase. 5-Bromo-6-aminouracil (5d), 5-cyano-6-[3-(methylamino)propyl]-uracil (5e), and 7-(2-aminoethyl)-pyrrolo[2,3-d]pyrimidine-2,4-dione (6c) inhibited dThdPase with IC50s of 7.6, 3.8 and 44.0 microM, respectively.

Antimetabolites, Antineoplastic↗

The role of mitogen-activated protein kinase in oxytocin-induced contraction of uterine smooth muscle in pregnant rat.

Oxytocin causes the rapid tyrosine phosphorylation of mitogen-activated protein (MAP) kinase in both human and rat puerperal uterine myometrial cultured cells. The potential role of the MAP kinase pathway in oxytocin action was investigated with the specific MAP kinase kinase (MEK) inhibitor, PD98059. Oxytocin stimulation of the tyrosine phosphorylation of MAP kinase in both human and rat cultured puerperal uterine cells was abolished by pretreatment of the cells with MEK inhibitor in a dose-dependent manner. Although MEK inhibitor had no effect on oxytocin-induced intracellular Ca2+ mobilization in either pregnant human or pregnant rat uterine cells, it partly inhibited oxytocin-induced pregnant rat uterine contraction in a dose-dependent manner. These results suggest that MAP kinase pathway may have some important roles in oxytocin-induced uterine contraction.

Animals↗

Thioredoxin: a redox-regulating cellular cofactor for glucocorticoid hormone action. Cross talk between endocrine control of stress response and cellular antioxidant defense system.

Adaptation to stress evokes a variety of biological responses, including activation of the hypothalamic-pituitary-adrenal (HPA) axis and synthesis of a panel of stress-response proteins at cellular levels: for example, expression of thioredoxin (TRX) is significantly induced under oxidative conditions. Glucocorticoids, as a peripheral effector of the HPA axis, exert their actions via interaction with a ligand-inducible transcription factor glucocorticoid receptor (GR). However, how these stress responses coordinately regulate cellular metabolism is still unknown. In this study, we demonstrated that either antisense TRX expression or cellular treatment with H2O2 negatively modulates GR function and decreases glucocorticoid-inducible gene expression. Impaired cellular response to glucocorticoids is rescued by overexpression of TRX, most possibly through the functional replenishment of the GR. Moreover, not only the ligand binding domain but the DNA binding domain of the GR is also suggested to be a direct target of TRX. Together, we here present evidence showing that cellular glucocorticoid responsiveness is coordinately modulated by redox state and TRX level and propose that cross talk between neuroendocrine control of stress responses and cellular antioxidant systems may be essential for mammalian adaptation processes.

Animals↗

Sensitive method for the determination of pulmonary surfactant phospholipid/sphingomyelin ratio in human amniotic fluids for the diagnosis of respiratory distress syndrome by thin-layer chromatography-immunostaining.

By TLC-immunostaining with the monoclonal antibody VJ-41, which preferentially reacted with sphingomyelin (Sm) and disaturated fatty acid-containing phosphatidyl choline (DSPC), Sm and surfactant phospholipid dipalmitoyl PC were only detected in the lipid extracts from human amniotic fluid. The method was useful in the selective and simultaneous determination of surfactant phospholipid and Sm concentrations in the amniotic fluids to determine the level of maturity of the lungs of the fetus. By measuring the density of spots visualized by TLC-immunostaining, we detected Sm at a sensitivity two times higher than that for dipalmitoyl PC using the antibody. More than 50 ng of dipalmitoyl PC and Sm was detected on the same TLC plate and the standard curves were linear up to 1 microgram of phospholipids. The method was applied to determine the surfactant phospholipid/Sm ratio in 20 microliter of the amniotic fluids obtained at delivery, and the amniotic fluids from the women who delivered a baby suffering from respiratory distress syndrome (RDS) were easily discriminated from the normal amniotic fluids. In an analysis of 200 microliter of amniotic fluids from 4 RDS cases and 16 normal baby cases, the mean DSPC/Sm ratios were 0.97 +/- 0.53 and 5.75 +/- 1.29, respectively.

Amniocentesis↗