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Biomedical subjects

H Kagawa

Publications and source records attributed to H Kagawa.

At least 55 records · Page 3Linked to original sources

Distribution and seasonal variations in levels of three native GnRHs in the brain and pituitary of perciform fish.

Specific and sensitive radioimmunoassays (RIAs) were newly developed for two types of gonadotropin-releasing hormone (GnRH), namely, seabream (sb) GnRH and chicken (c) GnRH-II. We employed these two RIAs together with a previously reported RIA for salmon (s) GnRH to study the presence and regional distribution of these three GnRHs in the brains and pituitaries of four perciform fishes (red seabream, Pagrus major; black seabream, Acanthopagrus schlegeli; striped knifejaw, Oplegnathus fasciatus; and Nile tilapia, Oreochromis niloticus), as well as clarify seasonal changes in levels of these GnRHs in the brain and pituitary of red seabream. All three GnRHs were found in brains of all fishes examined, with regional distributions in the brains of the three GnRHs being rather similar. sbGnRH was abundant in telencephalon and hypothalamus. cGnRH-II was concentrated from the middle to posterior part of the brain and distributed throughout the brain. sGnRH was concentrated in the olfactory bulb and distributed all over the brain, as was cGnRH-II. The dominant form of GnRH in the pituitary was sbGnRH, with levels 500- to 2400-fold higher than those of sGnRH, while cGnRH-II was undetectable in all four species. In the brain and pituitary of female red seabream, levels of both brain and pituitary sbGnRH increased from October (immature phase) and reached a peak in April (spawning phase), reflecting the increase in gonadosomatic index and vitellogenesis. However, levels of sbGnRH remained high only in the pituitary of completely regressed fish in June. Levels of both sGnRH and cGnRH-II in the brain were higher in the regressed phase and remained lower during the spawning phase. From these and previous results, it appears that sbGnRH is physiologically the most important form of GnRH in reproduction in red seabream and, probably, in other perciforms also.

Animals↗

Goat fetuses disconnected from the placenta, but reconnected to an artificial placenta, display intermittent breathing movements.

To investigate whether placental factors are involved in the intermittent breathing movements in goat fetuses, we assessed electrocortical activity (ECoA) and tracheal pressure in 5 fetuses (124-135 days) separated from the placenta and connected for 48 h to an extrauterine fetal incubation system that provided umbilical arteriovenous extracorporeal membrane oxygenation. The fetal physiological condition on this system was almost the same as that in utero for at least 48 h after the preparation. All fetuses showed intermittent low-voltage ECoA and breathing movements. The breathing movements occurred almost exclusively during periods of low- voltage ECoA. The proportions of time spent in low-voltage ECoA and breathing movements were 48-57% and 46-56%, respectively. In conclusion, breathing movements of fetuses on the extrauterine incubation system were episodic, suggesting that intermittent breathing movements are intrinsic to fetuses, independent of placenta-derived factors.

Animals↗

Effect of ticlopidine on platelet-derived microparticles in patients with connective tissue diseases.

We evaluated the plasma concentrations of platelet activation markers and platelet-derived microparticles (PMP) in patients with connective tissue diseases complaining of peripheral circulation disorders (n = 16) and studied the effect of ticlopidine hydrochloride (ticlopidine) on PMP generation. There were significant differences in the levels of PMP and a platelet activation marker between before and after treatment with ticlopidine (PMP: 695 +/- 393 vs. 354 +/- 206/10(4) platelets, p < 0. 01; platelet CD63: 9.13 +/- 5.64 vs. 5.22 +/- 2.74%, p < 0.05). On the other hand, markers of vascular endothelium, such as vascular endothelium-derived small vesicles and serum thrombomodulin levels, were not affected by the administration of ticlopidine. Levels of cytokines and soluble adhesion molecules remained unchanged by ticlopidine administration. These findings suggest that ticlopidine may be useful for the inhibition of PMP-dependent vascular damage in patients with connective tissue diseases complaining of peripheral circulation disorders.

Antigens, CD↗

Genetic analysis of HLA- and HPA-typing in idiopathic (autoimmune) thrombocytopenic purpura patients treated with cepharanthin.

We performed genetic analysis of human leukocyte antigen (HLA) and human platelet antigen (HPA) in 45 patients with cepharanthin-treated idiopathic thrombocytopenic purpura. HLA-typing was performed by the polymerase chain reaction-restriction fragment length polymorphism method, and HPA-typing by a polymerase chain reaction-sequence-specific primer method. There were 14 responders and 31 nonresponders. Responders included many patients who had already been treated with prednisolone. HLA-DRB1*0901 was significantly more common in responders than in nonresponders. In contrast, HLA-DRB1*0410 and DQB1*0401 were significantly more common in nonresponders. The a/b genotype of HPA-2a/2a (Ko(b)/Ko(b)) was significantly increased in responders. In contrast, HPA-2a/2b (Ko(b)/Ko(a)) and HPA-3a/3b (Bak(a)/Bak(b)) were significantly more common in nonresponders. These findings suggest that genetic studies of HLA and HPA can predict the response of idiopathic thrombocytopenic purpura to cepharanthin.

Adult↗

Effects of nilvadipine on cytokine-levels and soluble factors in collagen disease complicated with essential hypertension.

We examined some immunological parameters, particularly cytokines and soluble factors in collagen diseases complicated with essential hypertension. We also investigated the effects of Nilvadipine on immunological parameters after treatment with this drug for six months. The frequency of helper/inducer T cells (CD4+ CD8- cells, CD4+ CD45RA- cells) decreased in the peripheral blood on a 6 month treatment with nilvadipine. There was a significant decrease of suppressor/inducer T cells (CD4+ 45RA+ cells), and an insignificant decrease of activated T cells (CD3+ HLA-DR+ cells) and memory T cells (CD45RA- CD45RO+ cells) after treatment. Before treatment with Nilvadipine, interleukin-1beta, tumor necrosis factor-a, and interleukin-6 levels increased higher in the patients than in healthy volunteers. However, interleukin-1beta and interleukin-6 concentrations tended to decrease after treatment with Nilvadipine. Besides, tumor necrosis factor-alpha decreased significantly after treatment. The soluble interleukin-2 receptor concentrations also showed a decreased tendency after treatment, although high concentrations were found in the patients before treatment. In contrast, soluble human leukocyte antigen-1 and soluble thrombomodulin levels showed no significant change after treatment. These results suggest that Nilvadipine inhibits the generation of cytokines derived from activated T lymphocytes. Nilvadipine, calcium antagonist, may be useful for inhibition of vascular complication in collagen diseases.

Adult↗

[Fornix of vagina suspension for cystocele].

OBJECTIVE: Bladder neck hypermobility causes cystocele in middle to old elderly women. We developed an easy and useful surgical technique for cystocele. METHODS: Thirteen patients with cystocele (grade 2-4) were operated by fornix of the vagina suspension. Patients were placed on lithotomy position under general or spinal anesthesia. Lower midline or lower abdominal transverse incision was made to open the peritoneum and denuded vesicouterine pouch. Several nylon sutures were placed on the lateral side of exposed fornix of the vagina. These sutures were suspended to anterior layer of the rectus sheath. Fornix of the vagina was fixed to the rectus muscle, so the prolapsed bladder wall was pulled up in normal position. RESULTS: Operating time ranged from 15-110 minutes (average 73 minutes). Ten patients of thirteen were successful up to 2-43 months postoperatively. Cystocele recurred in three patients of thirteen. Two patients was re-operated by the same method, but one of them recurred. Two of three recurrent patients had grade 4 cystocele. CONCLUSION: Fornix of the vagina suspension for cystocele seems useful and promising because of easy procedure without serious morbidity, especially in elderly high-risk patients.

Aged↗

[Transurethral resection of the prostate for patients with dementia].

During the period from July 1995 to June 1996 we performed transurethral resection of the prostate (TURP) on 824 patients with benign prostatic hyperplasia (BPH). Among them, 13 were dementia patients between 74 and 96 years old; they presented with urinary hesitancy in 6, retention in 4, frequency in 2 and incontinence in 1 patient. Past history included stroke in 7, hypertension in 6, pulmonary tuberculosis in 4, diabetes in 3, asthma in 2, angina pectoris in 1, Parkinson's disease in 1, pneumonia in 1, and hepatitis in 1. Careful preoperative examination revealed that they were proper candidates for TURP. They underwent TURP under spinal anesthesia. The mean operative time was 34 min, ranging from 20 to 60 min. The adenoma resected weighed 24 g on the average, ranging from 7.5 to 48 g. During surgery, although hypotension was noted in 2 patients, there was no serious morbidity. Their mental condition was well controlled with ketamine and diazepam during and after surgery. Postoperative complications included acute myocardial infarction in 1, multiple gastric ulcer in 1, and decubitus in 1. None died within 3 months after TURP, 3 died there after, and 10 patients were alive at the mean follow-up period of 26 months. Six patients reported good urination, 3 reported some improvement in urination after surgery, although requiring intermittent catheterization and 1 developed mild incontinence. In conclusion, TURP appears to provide some benefit in selected patients with dementia and should not be considered to be a contraindication for such patients.

Aged↗

[Renal transplantation for patients with systemic lupus erythematosus: report of two cases].

Renal transplantation for patients with systemic lupus erythematosus (SLE) remains controversial. We performed living-tissue related renal transplantation on a 45-year-old woman with SLE and an eight-month history of hemodialysis. We also did cadaveric renal transplantation on a 41-year-old man with SLE and a 12-year history of hemodialysis. Serological tests including tests for antinuclear antibodies and complements were negative prior to surgery and throughout the course in both cases. The latter patients survived herpes-zoster virus infection in month 6 and bacterial pneumonia in month 9 after transplantation. Neither patient experienced any rejection or relapse of lupus nephritis after the procedure, and both maintained good renal allograft functions. The recurrence of lupus nephritis is reportedly extremely rare, i.e., with a possibility rate of less than 1% in transplant patients with burnt-out SLE. To the best of our knowledge, these cases are the 27th and 28th case reports of renal transplantation for SLE patients in Japanese literature.

Adult↗

Expression of functional tissue factor on small vesicles of lipopolysaccharide-stimulated human vascular endothelial cells.

We examined tissue factor expression on lipopolysaccharide-stimulated endothelial cells and their small vesicles by using specific antibodies and flow cytometry. Tissue factor functional activity was also assessed by activation of factor X. Endothelial cells were stimulated with 10 microg/ml of lipopolysaccharide in M-199/bovine serum albumin. Flow cytometry showed that expression of tissue factor on endothelial cells reached a maximum at 6 hours after stimulation, whereas that on small vesicles reached a maximum after 12 hours. Factor X activation mediated by factor VIIa and tissue factor was observed over a similar time course and was inhibited by the addition of antitissue factor antibody. Immunoelectron microscopy suggested that small vesicles with expression of some tissue factor were produced from the surface of endothelial cells. Our findings thus showed that tissue factor on endothelial cells produced by lipopolysaccharide stimulation was partly released to small vesicles. This may cause disseminated intravascular coagulation and related coagulation disorders.

Cells, Cultured↗

Clinical significance of HLA-DRB1*0410 in Japanese patients with idiopathic thrombocytopenic purpura.

We performed HLA-A, -B, and -C antigen and -DR DNA typing in 111 Japanese patients with idiopathic thrombocytopenic purpura (ITP). DRB1*0410 was significantly increased in ITP patients compared with healthy controls (relative risk = 9.52, P < .05), but the other DRB1*04 alleles showed no significant differences. On HLA-DR serotyping, patients with Vogt-Koyanagi-Harada disease (VKH) had a high frequency of DR4, so we compared the frequencies of DRB1*04 suballeles between ITP and VKH. The high frequency of DRB1*04 was dependent on DRB1*0405 in VKH, but on DRB1*0410 in ITP. Plasma autoantibodies were studied in 111 patients using a microtiter well assay. Thirty-six patients had anti-GPIIb/IIIa autoantibodies, and antibody positivity was associated with HLA-DR4 (29 of 36, 80.6% v 28 of 75, 37.3%) but not with DRB1*0410. When HLA-DR4 and DRB1*0410 were compared between patients with a good or poor response to prednisolone, HLA-DR4 was decreased and DRB1*0410 was significantly decreased (chi2 = 11.455, P < .01) in patients with a good response. In conclusion, this study showed that genetically determined factors influence the course of ITP. However, our findings should be considered preliminary because of possible racial differences in HLA status between Japanese and other ITP patients.

Adult↗

Immunocytochemical identification of two distinct gonadotropic cells (GTH I and GTH II) in the pituitary of bluefin tuna, Thunnus thynnus.

Immunocytochemical identification of GTH I and GTH II cells in the pituitary of the bluefin tuna (Thunnus thynnus) was performed using antisera specific for the common alpha-subunit and the two distinct beta-subunits of tuna (Thunnus obesus) GTH I and GTH II. Cells of the dorsal part of the proximal pars distalis (PPD), in close association with somatotrophs, displayed immunoreactivity of GTHIbeta. GTH IIbeta immunoreactivity was present in cells of the central part of the PPD and the external border of the pars intermedia. Anti-GTHalpha immunostained both GTH Ibeta- and GTH IIbeta-immunoreactive cells and also thyrotrophs. Both GTH Ibeta- and GTH IIbeta-immunoreactive cells were observed in immature bluefin tuna, although there were greater numbers of GTH IIbeta immunoreactive cells. These results suggest that GTH I and GTH II are synthesized in separate cells in the pituitary of the bluefin tuna. The localization and appearance of the two distinct gonadotropic cells of the tuna are compared with the salmonid arrangement.

Animals↗

GTH II but not GTH I induces final maturation and the development of maturational competence of oocytes of red seabream in vitro.

The effects of red seabream gonadotropins (PmGTH I and PmGTH II) on the induction in vitro of germinal vesicle breakdown (GVBD) and the development of maturational competence (responsiveness to maturation-inducing steroid) were examined in the oocytes of red seabream. PmGTH II was highly effective in inducing GVBD in both maturationally incompetent (45.6 +/- 3.2% GVBD at a concentration of 300 ng/ml) and competent oocytes (42.3 +/- 0.4% GVBD at a concentration of 300 ng/ml). 17,20beta-Dihydroxy-4-pregnen-3-one (DHP, 10 ng/ml) increased the frequency of GVBD induced by PmGTH II. PmGTH I (33, 100, 300, and 900 ng/ml) was unable to induce GVBD at any tested concentration in the presence or absence of DHP. Actinomycin D (1 microgram/ml) and cycloheximide (1 microgram/ml) totally inhibited the PmGTH II-induced GVBD in the presence and in the absence of DHP. Both PmGTH I and PmGTH II stimulated in vitro production of 11-ketotestosterone in sliced testes of red seabream in a similar potency. These results indicate that PmGTH II, but not PmGTH I, induces the final maturation of oocytes, as well as the development of the maturational competence of oocytes, in red seabream.

Animals↗

Differential developmental process of respective behavioral states in human fetuses.

The presence of behavioral states has been recognized in human fetuses. However, developmental process of fetal behavioral states remains to be clarified. In thirty-one normal pregnant women between 20 and 41 weeks' gestation, fetal movements were examined by using multiple ultrasonic machines. The entire period was divided into eye movement (EM), no eye movement (NEM), and unclassified periods according to the mode of appearance of rapid eye movements. We investigated changes in the ratio of EM and NEM periods and the incidence of various fetal movements in these periods. The ratio of EM periods increased stepwise between 20 and 32 weeks. The difference in the incidence of "startle" and jaw movements between EM and NEM periods was found at 24-27 and 32-35 weeks, respectively. We found a significant decrease in the incidence of total body movements exclusively in NEM periods at 36-39 weeks and a significant increase in the incidence of "rolling" in EM periods at 40-41 weeks. Eye opening was ultrasonographically recognized, providing evidence for awake state in the human fetus. This study revealed the characteristic appearance of fetal movements as related to the presence or absence of EM during the second half of pregnancy, and thereby pointed to differential development process of behavioral states of human fetuses.

Adult↗

HLA and HPA typing in idiopathic thrombocytopenic purpura patients treated with Kami-kihi-to.

We performed human leukocyte antigen (HLA) and human platelet antigen (HPA) in patients with Kami-kihi-to-responsive idiopathic thrombocytopenic purpura. The HLA-A2, A61 and Cw1 were significantly increased in responders compared with nonresponders, as were HLA DRB1 *0901, DRB1 *1502, and DPB1 *0501. In contrast, HLA DPB1 *0201 and DPB1 *0901 were significantly decreased in responders. The a/b genotype of HPA-2 and a/a genotype of HPA-3 were markedly increased in nonresponders, and anti-GPIb antibody was also increased. These results suggest that HLA, HPA, and anti-GP antibody studies may predict the response of idiopathic thrombocytopenic purpura to Kami-kihi-to.

Antigens, Human Platelet↗

[Anti-fibrinogen antibody detected in a patient with systemic lupus erythematosus and disseminated intravascular coagulation].

A 22-year-old woman was admitted to our hospital with fever, generalized lymphadenopathy, and pancytopenia in February 1995. She was diagnosed as having systemic lupus erythematosus (SLE) based on positivity for anti-nuclear antibody, and polyarthritis among other findings. A diagnosis of disseminated intravascular coagulation (DIC) was made based on the increase of FDP and other data (DIC score: 7). We also detected an anti-fibrinogen antibody. Lymph node biopsy revealed subacute necrotizing inflammation and there were on signs of the hemophagocytic phenomenon in bone marrow. The DIC score improved and the anti-fibrinogen antibody disappeared in association with the response of SLE to prednisolone therapy. The onset of SLE associated with DIC has never been reported before, as far as we could determine. The mechanism of DIC associated with SLE may be related to endothelial damage caused by immune complexes.

Adult↗

Effect of cilostazol on soluble adhesion molecules and platelet-derived microparticles in patients with diabetes.

We evaluated the plasma concentrations of soluble adhesion molecules and platelet-derived microparticles (PMP) in patients with non-insulin dependent diabetes mellitus (NIDDM) and studied the effect of cilostazol on PMP generation. There were differences in the levels of soluble adhesion molecules between NIDDM patients (N = 43) and the control subjects (N = 30) (soluble thrombomodulin: 11.5+/-5.3 vs. 7.0+/-1.2 TU/ml, p<0.0001; soluble vascular cell adhesion molecule-1: 708+/-203 vs. 492+/-113 ng/dl, p<0.0001; soluble intercellular cell adhesion molecules- 1: 274+/-65 vs. 206+/-48 ng/dl, p<0.0001; soluble P-selectin: 194+/-85 vs. 125+/-43 ng/dl, p<0.0001). There were also differences in the levels of PMP and platelet activation markers between NIDDM patients and the controls (PMP: 943+/-504 vs. 488+/-219/10(4) plt, p<0.0001; platelet CD62P: 9.2+/-4.6 vs. 4.4+/-4.3%, p<0.001; platelet CD63: 10.2+/-4.5 vs. 4.5+/-3.3%, p<0.0001; platelet annexin V: 9.1+/-3.9 vs. 5.3+/-3.8%, p<0.001). To study the release of PMP into plasma, a modified cone-and-plate viscometer was used. Increased release of PMP from platelets was observed in diabetic plasma compared to normal plasma under high shear stress conditions (2,672+/-645 vs. 1,498+/-386/10(4) plt, p<0.05). Therefore, one cause of PMP elevation in NIDDM may be high shear stress. The levels of PMP, activated platelets, and soluble adhesion molecules all decreased significantly after treatment with cilostazol. These results suggest that cilostazol may be useful for the inhibition of both PMP-dependent and -independent vascular damage in NIDDM.

Adult↗

An abnormal ketamine response in mutants defective in the ryanodine receptor gene ryr-1 (unc-68) of Caenorhabditis elegans.

To characterize excitation-contraction coupling in Caenorhabditis elegans, we applied two approaches. First, we isolated a mutant having abnormal responses to ketamine, an anesthetic in vertebrates. The novel mutation unc-68(kh30) (isolated as kra-1(kh30)), exhibited strict ketamine-dependent convulsions followed by paralysis. Second, we cloned the C. elegans ryanodine receptor gene ryr-1 that is located near the center of chromosome V. ryr-1 consists of 46 exons, which encode a predicted protein of 5071 amino acid residues that is homologous to Drosophila and vertebrate ryanodine receptors. ryr-1 promoter/lacZ plasmids were expressed in body-wall and pharyngeal muscles. Non-muscle cell expression may be seen with a truncated promoter. In addition, we show that the unc-68/kra-1(kh30) mutation is a Ser1444 Asn substitution at a putative protein kinase C phosphorylation site in ryr-1, and that unc-68(e540) contains a splice acceptor mutation that creates a premature stop codon in the ryr-1 gene. We confirmed that unc-68(e540) is a mutation in ryr-1 by injecting the complete ryr-1 gene into unc-68(e540) animals and recovering wild-type progeny. Results presented here will be useful in studying the structure and function of ryanodine receptors in excitation-contraction coupling and in understanding the evolution of ryanodine receptor tissue specificity.

Amino Acid Sequence↗

Tyrosine phosphorylation and p72syk activation by an anti-glycoprotein Ib monoclonal antibody.

NNKY5-5, an IgG monoclonal antibody directed against the von Willebrand factor-binding domain of glycoprotein (GP) Ib alpha, induced weak but irreversible aggregation (or association) of platelets in citrate-anticoagulated platelet-rich plasma. This phenomenon was defined as small aggregate formation (SAF). Platelets in hirudin-anticoagulated plasma or washed platelets showed little response to NNKY5-5 alone, but the antibody potentiated aggregation induced by low concentrations of adenosine diphosphate or platelet-activating factor. NNKY5-5 did not induce granule release or intracellular Ca2+ mobilization. However, NNKY5-5 caused tyrosine phosphorylation of a 64-kD protein and activation of a tyrosine kinase, p72syk. An anti-Fc gamma II receptor antibody had no effect on SAF, suggesting that NNKY5-5 activated platelets by interacting with glycoprotein Ib. Fab' fragments of NNKY5-5 did not induce SAF, but potentiated aggregation induced by other agonists. The Fab' fragment of NNKY5-5 induced the activation of p72syk, suggesting that such activation was independent of the Fc gamma II receptor. Cross-linking of the receptor-bound Fab' fragment of NNKY5-5 with a secondary antibody induced SAF. GRGDS peptide, chelation of extracellular Ca2+, and an anti-GPIIb/IIIa antibody inhibited NNKY5-5-induced SAF, but had no effect on 64-kD protein tyrosine phosphorylation or p72syk activations. Various inhibitors, including aspirin and protein kinase C, had no effect on SAF, protein tyrosine phosphorylation, or p72syk activation. In contrast, tyrphostin 47, a potent tyrosine kinase inhibitor, inhibited NNKY5-5-induced SAF as well as tyrosine phosphorylation and p72syk activation. Our findings suggest that binding of NNKY5-5 to GPIb potentiates platelet aggregation by facilitating the interaction between fibrinogen and GPIIb/IIIa through a mechanism associated with p72syk activation and tyrosine phosphorylation of a 64-kD protein.

Antibodies, Monoclonal↗