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Biomedical subjects

H Kaneko

Publications and source records attributed to H Kaneko.

At least 19 recordsLinked to original sources

Differences in alpha 2u-globulins increased in male rat kidneys following treatment with several alpha 2u-globulin accumulating agents: cystein protease(s) play(s) an important role in production of kidney-type-alpha 2u-globulin.

Effects of alpha 2u-globulin accumulating agents on alpha 2u-globulins in rat kidneys were examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting analysis. Treatment of male animals with decalin (150 mg/kg), 2,2,4-trimethylpentane (50 mg/kg), isophorone (150 mg/kg), d-limonene (150 mg/kg) or 1,4-dichlorobenzene (150 mg/kg) by gavage for 14 consecutive days in each case resulted in a marked intensification of a protein band corresponding to kidney-type-alpha 2u-globulin, with a molecular mass calculated to be approximately 16 kDa. However, intraperitoneal treatment with leupeptin and E-64 (two times 0.07 mmol/kg, for each), well known cystein protease inhibitors, while only slightly increasing this kidney-type-alpha 2u-globulin band, caused the intensification of a approximately 19-kDa molecular mass protein band which was revealed to be a native-type-alpha 2u-globulin by SDS-PAGE and immunoblotting. These results indicated that at least two types of alpha 2u-globulin can be increased in male rat kidney by chemical treatment. Moreover, cystein protease(s) appear(s) to play an important role in the degradation of alpha 2u-globulin and particularly in the conversion of native-type-alpha 2u-globulin to kidney-type-alpha 2u-globulin in rat kidneys.

Alpha-Globulins

Helicobacter pylori infection induces a decrease in immunoreactive-somatostatin concentrations of human stomach.

Immunoreactive-somatostatin (ir-somatostatin) concentrations of the gastric mucosa and gastric juice with Helicobacter pylori infection were measured in the human stomach. One hundred seventy-one patients (106 males, 65 females; mean age, 52.0; range, 19-84 years) were registered. Gastric juice and mucosa were obtained with the usual endoscopy procedure. Somatostatin concentration was measured by radioimmunoassay. The ir-somatostatin concentrations in the H. pylori-negative group were significantly higher than in the positive group gastric mucosa, whereas its levels in gastric juice tended to decrease with H. pylori infection. There was an inverse correlation between luminal ammonia levels and ir-somatostatin concentrations of the gastric mucosa. On the other hand, ir-somatostatin concentrations of the gastric mucosa significantly decreased with chronic and active inflammatory change. This decrease was not correlated with the grade of active inflammation, which was in close relation to H. pylori infection, but with the grade of chronic inflammation. These results indicate that H. pylori may reduce ir-somatostatin concentrations of the human stomach and that its effect is partly mediated via luminal ammonia produced by H. pylori.

Adult

Dedifferentiated leiomyosarcoma of the intestinal tract: histological, ultrastructural and immunohistochemical examinations.

Six cases of dedifferentiated leiomyosarcoma of the small and large bowel are presented with histological, ultrastructural and immunohistochemical examination. One case arose in the jejunum, two in the ileum, and the other three in the large intestine. The tumours were submucosal in four cases with large areas of ulceration; two were polypoid. Four tumours showed typical leiomyosarcomatous appearance with dedifferentiated components and two were typical leiomyosarcomas at the primary site with differentiated components only in metastatic foci. By immunohistochemistry, typical leiomyosarcomatous areas showed a positive reaction for muscle-specific actin (MSA), MB1, MB2 and myosin. In contrast, desmin-positive cells were scattered throughout the tumour or were not present. Tumour cells in dedifferentiated components were positive for alpha-1-antitrypsin and alpha-1-antichymotrypsin in all cases but one; neuron specific enolase, MB1, MB2 and myosin were positive with variety. MSA was faintly positive in only a few tumour cells of two cases and desmin was not detected in any of the cases studied. Ultrastructurally, tumour cells in typical leiomyosarcomatous areas demonstrated evident smooth muscle features, although in dedifferentiated areas they lacked such features except in one case. Our results indicate that dedifferentiated elements may derive from ordinary leiomyosarcoma and loose muscle features due to dedifferentiation.

Aged

Central catecholamine, sympathetic nerve and vascular protein in the acute phase of two-kidney, one-clip renovascular hypertension in rats.

Incorporation of 3H-proline into the non-collagenous protein in mesenteric arteries in two-kidney, one-clip hypertensive rats was greater than that in normotensive rats. Splanchnicotomy predominantly over the root of mesenteric arteries or intracranioventricular injection of 6-hydroxydopamine prevented the development of hypertension in 2K-1C rats concomitant with the reduction of incorporation of 3H-proline into the non-collagenous protein in mesenteric arteries. The content of norepinephrine in the hypothalamus in 2K-1C rats was lower than that in normotensive control rats. These findings indicate that increased non-collagenous protein synthesis in mesenteric arteries or low level of hypothalamic norepinephrine has facilitative effects on the development of 2K-1C hypertension.

Animals

Effect of luminal administration of thyrotropin-releasing hormone or somatostatin on gastric pH and interaction of these peptides in rats.

The effect of intraluminal administration of thyrotropin-releasing hormone (TRH) on gastric pH and release of luminal somatostatin, and a possible interrelationship between TRH and somatostatin in the rat stomach were studied. TRH was administered into the stomach via an intragastric tube at various doses (50 pg/kg-10 micrograms/kg) and gastric pH was measured after 15 min. The intraluminal administration of TRH significantly decreased gastric pH at doses over 1.0 ng/kg. Time-course studies at a dose of 100 ng/kg TRH exhibited a significant decrease in gastric pH at 15, 30 and 60 min. Furthermore, TRH administration caused a significant increase in immunoreactive-somatostatin (ir-somatostatin) concentrations in the gastric wall and a significant decrease in ir-somatostatin concentrations in the gastric juice. On the other hand, intraluminal administration of somatostatin caused a significant increase in ir-TRH concentrations in the gastric wall and a significant decrease in ir-TRH concentrations in the gastric juice, and significantly raised gastric pH at 5 min. These findings suggest that luminal TRH may exert a regulatory effect on gastric acid secretion, and that TRH may have a possible interaction with somatostatin in the modulation of gastric acid secretion.

Animals

Tissue-specific expression, induction, and inhibition through metabolic intermediate-complex formation of guinea pig cytochrome P450 belonging to the CYP2B subfamily.

The tissue-specific expression and induction of P450GP-1, a constitutive form of cytochrome P450 of the guinea pig classified into the CYP2B subfamily, were studied. Prior to these studies, a P450 form (P450GP-1 PB) was purified from phenobarbital-treated guinea pigs and the properties were compared with those of the P450GP-1. This form was judged to be the same as P450GP-1 existing in untreated animals by comparisons of their N-terminal amino acid sequences, peptide maps, and affinities toward anti-P450GP-1 antibody. Immunostaining of P450GP-1 revealed that the lung and small intestine as well as the liver of untreated guinea pigs contain P450GP-1, while none or only small amounts of this P450 form were observed in the kidney, heart, spleen, urinary bladder, and testis. The amount of liver P450GP-1 protein expressed in untreated guinea pigs was estimated to be 19.4% of the total cytochrome P450 and this form was increased 1.7-fold by phenobarbital treatment. Similarly, intestinal P450GP-1 was increased by phenobarbital treatment. However, lung P450GP-1 was not increased by the treatment. It was also observed that the liver P450GP-1 is induced with SKF-525A to the same extent as with phenobarbital. On the other hand, dexamethsone, p,p'-dichlorodiphenyltrichloroethane, and isosafrole showed no or only a weak ability to increase the liver P450GP-1 content. The drug-metabolizing activities in the liver microsomes of SKF-525A-pretreated guinea pigs were lower than those in phenobarbital-treated animals, although the P450GP-1 protein was induced equally by these treatments. The low activities of SKF-525A-treated animals in the drug metabolisms were attributed to the formation of the metabolic-intermediate complex between P450GP-1 and SKF-525A metabolite. These results permitted us to conclude that the tissue specificity in the expression of guinea pig P450 belonging to the CYP2B subfamily and the inducibility with chemicals are similar to those of rat CYP2B1, although the constitutive expression of guinea pig liver P450GP-1 is much higher than that of CYP2B1.

Amino Acid Sequence

Changes in peripheral levels of bioactive and immunoreactive inhibin, estradiol-17 beta, progesterone, luteinizing hormone, and follicle-stimulating hormone associated with follicular development in cows induced to superovulate with equine chorionic gonadotropin.

Changes in concentrations of bioactive and immunoreactive (ir-) inhibin, estradiol-17 beta, progesterone, LH, and FSH in peripheral blood were determined in cows induced to superovulate with eCG. The pattern of follicular growth was also characterized by daily ultrasonographic examination. Hormonal profiles and follicular development during the intact estrous cycle of the same animals before eCG treatment served as controls. Equine CG increased the number of follicles of various sizes (small, greater than or equal to 4 less than 7, medium, greater than or equal to 7 less than 10; large, greater than or equal to 10 mm in diameter) by 4 days after administration. The second growth of large follicles occurred within 1 day after superovulation. Inhibin bioactivity in jugular vein blood was detectable 48 h after eCG injection (44 h before LH peak), whereas it was not detected before administration of eCG or during control cycles. Circulating levels of bioactive inhibin further increased during the two waves of growth of large follicles. The highest activity of inhibin was noted at the time of the preovulatory LH peak (0 h). Thereafter, bioactivity of inhibin in peripheral plasma dropped from 0 to 24 h after the LH peak, and the activity increased again at 72 h compared to the value at -44 h. Plasma levels of ir-inhibin showed a pattern similar to changes in bioactive inhibin in the eCG-treated cows. Plasma concentrations of estradiol-17 beta also increased concomitantly with two waves of growth of large follicles. There was no correlation between plasma levels of progesterone and inhibin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Direct injection analysis of melphalan in plasma using column-switching high-performance liquid chromatography.

An automated column-switching high-performance liquid chromatographic (HPLC) method with ultraviolet detection is described for a simple and rapid determination of melphalan, an alkylating agent, in human plasma following direct sample injection. The system consists of a pretreatment column and an analytical column connected in series via a switching valve. Plasma samples are loaded onto a pretreatment column with an aqueous mobile phase, with which the sample to be analyzed is retained and the solubilized plasma proteins are flushed to be discarded. The retained compound is eluted from the pretreatment column onto the analytical column by using the chromatographic mobile phase with a higher elution capacity. The column-switching technique can be used to achieve an automated assay. Analytical recovery of the compound was 99.1%, and the coefficients of both intra- and interday variations did not exceed 3.5%. The detection limit was 10 ng/ml for the compound. Recovery of melphalan in plasma was only 2.1% after 4 weeks at 25 degrees C, as compared to 24.5% at 5 degrees C and 100.1% at -20 degrees C.

Adolescent

Common variable immunodeficiency with increased surface IgM-positive double-bearing B cells.

We report a case of common variable immunodeficiency (CVI) that shows low levels of IgG and IgA, but a normal quantitative or qualitative level of IgM. T-cell functions were not disturbed. Increased numbers of surface IgM (sIgM) and sIgD, sIgM and sIgG, sIgM and sIgA double-bearing B cells were observed as compared with a control. No IgG and IgA induction upon stimulation with Staphylococcus aureus Cowan I (SAC) and recombinant interleukin-2 (rIL-2), or pokeweed mitogen (PWM) and rIL-4 or rIL-6 was observed, although there was proliferation. Although mu mRNA was expressed as much as in a healthy control, transcription of gamma mRNA and alpha mRNA was very low. Furthermore, no enhanced effects of gamma mRNA and alpha mRNA were recognized upon stimulation with rIL-4 and rIL-6. These results suggest that the patient's B cells might be defective at the switching process from mu, mu and delta, mu and gamma to gamma or mu and alpha to alpha.

Antibody Formation

Diversity in DNA rearrangements and in RNA expressions of immunoglobulin gene on common variable immunodeficiency.

Six heterogeneous common variable immunodeficiency (CVID) patients were analysed for germ-line DNA, DNA rearrangements, and RNA expressions of immunoglobulin (Ig) gene by Southern or northern blotting using appropriate probes. We detected no polymorphism in neutrophil DNA hybridized to a C mu and a C gamma probe. In three patients, both serum Ig and Ig-bearing cells were scarcely detected, and by northern hybridization methods, neither mu mRNA, gamma mRNA, alpha mRNA nor kappa mRNA was detected. However, one Epstein-Barr virus-transformed B lymphoblastoid cell line (LCL) of these three patients was different from the germ line in the region of JH, C gamma, and C kappa, and expressed mu mRNA at a higher level. The B cell defects of these three patients lay on the B cell maturation stage similar to X-linked agammaglobulinaemia (XLA). In two others among the six CVID patients, serum IgM and IgM-bearing cells were detected to a certain degree, and by northern hybridization, mu mRNA was detected at a lower level, but neither mu mRNA, alpha mRNA, nor kappa mRNA was detected. One LCL of these two patients could express mu mRNA at the normal level. In the last patient, the serum IgM was normal, serum IgG and IgA were somewhat low, Ig-bearing cells were normal, mu mRNA and kappa mRNA were detected at the normal level, and gamma mRNA and alpha mRNA were detected at a lower level. The defect of this patient affected the class switch stage. These results showed that primary B cell defects in CVID occurred at several B cell differentiation stages which could be classified by expression of the Ig gene, and at the degree of clonal diversity in the B cell repertoire. Furthermore, this study provides support for the idea that the CVID defect is related to a more generalized cellular function, such as regulating the proliferation and/or clonal expansion of cells of the B lymphoid lineage.

Antibody Formation

Effect of serotonin on the immunoreactive thyrotropin-releasing hormone concentrations of the rat stomach.

The effects of serotonin and its related compounds on immunoreactive thyrotropin-releasing hormone (ir-TRH) concentrations of the rat stomach wall and gastric juice were studied. Either serotonin, cyproheptadine or GR38032F was injected intraperitoneally, and the rats were decapitated at various times after the injection. ir-TRH concentrations of the stomach wall and gastric juice were measured by radioimmunoassay, and gastric serotonin concentrations were measured by HPLC. ir-TRH concentrations of the stomach wall decreased, and ir-TRH concentrations of gastric juice increased significantly after serotonin injection. On the other hand, both cyproheptadine and GR38032F did not affect ir-TRH concentrations of the stomach. The effects of serotonin on ir-TRH concentrations of the stomach were significantly blocked by the pretreatment of cyproheptadine and GR38032F. The reciprocal changes of gastric ir-TRH and serotonin concentrations were observed without changes in gastric juice pH. These findings suggest that serotonin stimulates ir-TRH release from the stomach wall into gastric juice, and the effects of serotonin on ir-TRH release may be partly mediated via 5-HT2- and 5-HT3-receptors.

Animals

[Mammalian toxicity of empenthrin (Vaporthrin, S-2852F)].

1. Acute toxicity: Empenthrin ((RS)-(EZ)-1-ethynyl-2-methyl-2-pentenyl (1R)-cis/trans-chrysanthemate) caused some toxic signs such as muscular fibrillation, tremor, hypersensitivity, decrease of spontaneous activity, ataxic gait, lymb paralysis, irregular respiration, excretion of oily substance, loose stool and urinary incontinence in oral acute toxicity studies at 1000 mg/kg and above in rats, and at 2000 mg/kg and above in mice. The oral LD50 value was estimated greater than 5000 mg/kg (male) and greater than 3500 mg/kg (female) in rats and greater than 3500 mg/kg (both sexes) in mice. In both rats and mice, the toxic signs were not found at 2000 mg/kg by dermal administration. The dermal LD50 value was estimated greater than 2000 mg/kg (both sexes) in both rats and mice. The LC50 value in rats for the acute inhalation toxicity of empenthrin was estimated to be greater than 4610 mg/m3 for both sexes. The LC50 value in mice was determined to be 2700 mg/m3 for male and 2300 mg/m3 for female. Mice showed higher sensitivity to empenthrin than rats. 2. Reproductive and developmental toxicity: Empenthrin was orally administered to fetal organogenesis periods of rats at the dose levels of 50, 150 and 500 mg/kg, and of rabbits at 100, 300 and 1000mg/kg. Maternal toxicity was found at 500 mg/kg in rats and at 300 mg/kg or more in rabbits. There were no teratogenicity, no embryotoxicity and no fetal retardation in rats or rabbits. In addition, there were no adverse effects on F1 pups growth, development or reproductive performance. 3. Subchronic toxicity: Empenthrin was orally administered to male and female SD rats at dose levels of 0 (corn oil), 10, 100 and 300 mg/kg for 26 weeks. Clinical signs, body weight, food and water consumption were monitered, and hematological, blood biochemical, ophthalmological and histopathological examination were carried out. As a result, changes related to administration of empenthrin were observed mainly in the liver and kidneys in rats receiving 100 mg/kg or more. Therefore, the no-effect-level of empenthrin is determined to be 10 mg/kg in both sexes of rats in this study.

Administration, Oral

[Clinical studies of recombinant human granulocyte colony-stimulating factor in elderly patients with malignant lymphoma].

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was given in combination with chemotherapy in elderly patients (greater than or equal to 65 years old) with malignant lymphoma, and the therapeutic efficacy and the incidence of side effects were determined. The subjects consisted of 5 males and 8 females with a median age of 74 years. One patient had Hodgkin's disease and 12 had non-Hodgkin's lymphoma. Regarding lymphoma stage, 2 were in stage II, 3 were in stage III, and 8 were in stage IV. The chemotherapy used was COP-BLAM in 8 patients, COP-BLAM III in 2, IMV-triple P in 2, and ACVP-16 in 1. Treatment with rhG-CSF (1.5 micrograms/kg/day) was commenced during or after the 2nd course of chemotherapy when the neutrophil count dropped to greater than or equal to 1,000/microliters, and was continued until the recovery of either the neutrophil or leukocyte count to 10,000/microliters or 20,000/microliters, respectively. The neutrophil nadir in the non-G-CSF group was 367.3 +/- 231.6/microliters. In the G-CSF group it was 754.6 +/- 116.4/microliters for the second course, with the difference between the 2 groups being significant (p less than or equal to 0.05). Also, the following time periods were significantly shorter in the G-CSF group than the non-G-CSF group: 1) the duration of a neutrophil count less than 1,000/microliters, 2) the duration of fever (greater than or equal to 37.5 degrees C), and 3) the time to recovery from the neutrophil nadir.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

[Non-Hodgkin's lymphoma in an elderly patient complicated by cyclophosphamide-induced allergic hepatic dysfunction].

A 77-year-old male presented at our Department of Urology in August 1990 with a gradually enlarging swelling in the right scrotum. On August 21, right high orchietomy was performed. This was diagnosed histologically as non-Hodgkin's lymphoma (diffuse large cell type), and the patient was transferred to our department on September 11 for further examination and treatment. As enlargement of the lymph nodes around the abdominal aorta was evident, it was diagnosed as stage IIA according to the Ann Arbor Classification. Beginning on September 21, three courses of COP-BLAM therapy (CPM, VCR, PDN, BLM, ADR, PCZ) were administered (the third course started on November 8) to achieve complete remission. Hepatic dysfunction appeared, however, from November 16, and by November 19, GOT and GPT increased to 6700 and 2120, respectively, with aggravation of jaundice. PDN therapy was instituted, and GOT and GPT improved gradually, but jaundice did not improve. On December 22, laparoscopy was performed, and liver biopsy produced histologic findings of drug-induced hepatitis. Further, lymphoblastic response was positive for CPM. Hepatic failure occurred on December 29, and plasma exchange was performed, but it failed to improve the condition, and the patient died on January 15. We described a case of non-Hodgkin's lymphoma complicated by hepatic dysfunction, probably induced by CPM, in an elderly patient who died to hepatic failure.

Aged

[Elderly non-Hodgkin's lymphoma presenting with pulmonary squamous cell carcinoma as a complication of chemotherapy for malignant lymphoma].

The authors report a case of pulmonary squamous cell carcinoma which occurred after chemotherapy of non-Hodgkin's lymphoma (NHL). A 76-year-old man, who was admitted to our department because of swelling of cervical lymph nodes, was diagnosed as having NHL (follicular mixed cell lymphoma). He was treated with 11 courses of CHOP therapy. Thereafter, chemotherapy including ifosfamide was carried out for approximately three years. In June, 1991, he was readmitted to our department because of swelling and pain in his left thigh and an abnormal shadow on chest X-ray. Chest CT demonstrated a cavitated shadow (about 5 cm in diameter) with an irregular margin in right S1, which was suggested to be lung cancer or pulmonary infiltration of malignant lymphoma. Bronchoscopy, which was carried out on July 12, showed bloody sputa from the right B1 ramus and markedly reddened mucosa at the orifice of the right upper bronchus. Sputum cytology revealed no malignancy. ACVP-16 chemotherapy including ara-C, CBDCA and VP-16 was initiated on July 14 because of enlarged superficial lymph nodes. On July 18, he fell out of bed and fractured his left femur. He also suffered from respiratory failure. He died of pulmonary haemorrhage on July 26. Autopsy revealed pulmonary squamous cell carcinoma. The occurrence of pulmonary squamous cell carcinoma is rare after the chemotherapy of malignant lymphoma.

Aged

[Experimental study on the effect of injection with anticancer agent-oil suspension].

Local injection of an anticancer agent guided by endoscopy is thought to be effective for cancerous lesion associated with lymph node metastasis, if the anticancer drugs are drained into the lymph nodes. In the experimental study, anticancer drug-oil (nimustine-Lipiodol) (N-L) suspension (5 mg/ml) was injected into the tumor (Lewis lung cancer) that had been implanted sub dorsally in mice (57 black/6 mice) for the purpose of finding out the antitumor effect on the primary lesion. Then it was injected into sarcoma-180 that had been implanted into hind feet of mice (ICR mice) for the purpose of finding out the antitumor effect on metastatic lymph nodes. The results showed that the N-L suspension was effective for the primary cancerous lesion and metastatic lesions.

Animals

[Effect of a long-term oral ammonia administration on immunoreactive-somatostatin concentrations of rat stomach].

The effect of a long-term oral ammonia administration on immunoreactive-somatostatin concentrations was investigated in rat stomach. The gastric ir-somatostatin concentrations in the group treated with 0.01% ammonia (pH 9.6) for four weeks were significantly higher than those in both the group treated with 0.1% ammonia (pH 10.4), 0.1 mM-NaOH (pH 9.6), or distilled water (pH 7.0) for four weeks and the group treated with 0.01% ammonia for two weeks. On the contrary, ir-somatostatin levels in the gastric juice and serum tended to decrease with ammonia administration. Further, ammonia administration significantly induced the decrease in mucosal thickness in the pyloric gland area and parietal cell numbers in a dose- and time-dependent manner. From these findings, it was suggested that a long-term oral treatment with 0.01% ammonia, which was clinically estimated as the concentration of the gastric juice in patients with Helicobacter pylori infection, induced not only atrophic changes on gastric mucosa, but the inhibitory effect on somatostatin secretion in rat stomach.

Administration, Oral

[Mitral valve surgery using combined superior-transseptal approach to the left atrium].

Although various approaches to the mitral valve surgery have been tried in the past, it still may be difficult to obtain a good surgical field, particularly in cases of small left atrium or reoperation. We performed mitral valve surgery in 6 patients using the combined superior-transseptal approach to the left atrium proposed by Berreklouw. Exposure of the mitral valve was excellent and the operative procedure was simple in all cases. There were no differences in bleeding volume, length of operation or complication of arrhythmia between patients treated with this new approach and a group treated with conventional approach in our institute.

Adult