Biomedical subjects

S Hamano

Publications and source records attributed to S Hamano.

At least 19 recordsLinked to original sources

PubMed2003

High expression of the novel endothelin-converting enzyme genes, Nbla03145/ECEL1alpha and beta, is associated with favorable prognosis in human neuroblastomas.

The clinicobiological feature of neuroblastoma is enigmatic because spontaneous regression often occurs in early stages of tumors of the patients under 1 year of age, while rapid growth usually occurs in the tumors of the patients over 1 year of age. Such difference in the clinical behavior may be caused by the difference in the pattern of gene expression among the subsets of neuroblastoma. To understand the molecular basis of neuroblastoma biology, we decided to identify the novel genes expressed differentially between favorable and unfavorable neuroblastomas. The oligo-capping cDNA libraries were constructed from different subsets of neuroblastomas. After random selection and DNA sequencing, the differentially expressed genes between favorable and unfavorable neuroblastomas were screened by reverse transcriptase-PCR. The clinical significance of gene expression was evaluated based on the results of Northern blot analysis. We have identified a novel gene Nbla03145 (alpha), also cloned and termed by another group as ECEL1, which encodes a new member of putative zinc-binding metalloendopeptidase (endothelin-converting enzyme) with unknown substrate. We also cloned a COOH-terminally truncated Nbla03145/ECEL1beta which is expressed only in thymus. In primary NBLs, the alpha isoform is more preferentially expressed than the beta isoform. High levels of Nbla03145/ECEL1 expression were significantly correlated with a younger age (p=0.0005), lower stages (p=0.0019), high level of TrkA expression (p</=0.00005), a single copy of MYCN (p<0.00005) and the tumors found by mass screening (p<0.00005). Decreased expression of Nbla03145/ECEL1 mRNA was significantly associated with poor prognosis (log-rank test: p=0.012). The present results have shown that expression of Nbla03145/ECEL1 is a novel prognostic marker of neuroblastoma. Further analysis of the gene may also give a cue to the understanding of the role of endothelin-like signaling in neuroblastoma and to the development of diagnostic and therapeutic strategies against aggressive tumors.

Amino Acid Sequence↗

PubMed2002

Embryonic and calving losses in bovine mixed-breed twins induced by transfer of in vitro-produced embryos to bred recipients.

One or two in vitro-produced (IVP) Japanese Black (JB) cattle embryos at 8 days after in vitro fertilization were transferred to the contralateral uterine horn of previously bred Japanese Shorthorn (JSH) or JSH-JB cross recipients, and then the occurrence of early embryonic death, abortion during mid- and late gestation, and calving loss were recorded. The survival rate of embryos, including indigenous ones, was not affected by the number of embryos transferred, and a significantly higher twinning rate (68% of pregnant recipients at 80 days after transfer) was achieved when two IVP embryos were transferred, as compared with the rate when one IVP embryo was transferred (24%). In late ET (recipients at 8.5-9.0 days after the onset of oestrus), the embryo survival rate (22%) and the pregnancy rate (42%) at 80 days after ET were significantly lower than those rates in the synchronous ET (recipients at 8.0 days after the onset of oestrus; 47 and 79%, respectively). In the early ET (recipients at 6.0-7.5 days after the onset of oestrus), no significant differences from the synchronous ET were detected in these rates. Twenty-six percent of twin pregnant recipients were aborted during mid- or late-pregnancy, and 39% of twin calves were stillborn. The mean gestation length of the twin-bearing JSH dams (276 days) was 1 week shorter than that of the single-bearing JSH dams, and it was 2 weeks shorter than that of the JB dams bearing a single JB calf derived from the IVP embryos. The longer gestation length of single JB calves derived from IVP embryos resulted in a significantly higher mean birth weight than that of in vivo control calves with the standard length of gestation. In conclusion, the number of embryos to be transferred did not affect the embryo survival rate, and the transfer of two IVP embryos to previously inseminated recipients induced a significantly higher twinning rate during early pregnancy than that of one IVP embryo transfer. The incidence of embryonic losses during early pregnancy increased when Day 8 embryos were transferred to the recipients later in the oestrous cycle (>8.0 days). The results suggested that one cause of the high rate of abortions and stillbirths in twin-bearing dams is the difference in the mean gestation length between the native JSH and JB foetuses derived from transferred IVP embryos.

Abortion, Spontaneous↗

PubMed2002

Frequent mutations of SCN1A in severe myoclonic epilepsy in infancy.

Mutations in the neuronal voltage-gated sodium channel alpha-subunit type I gene (SCN1A) were found responsible for severe myoclonic epilepsy in infancy (SMEI). The authors describe novel mutations of SCN1A in Japanese patients with SMEI. They screened 12 unrelated patients and a pair of monozygotic twins and detected 10 mutations that lead to truncation of the protein.

Diseases in Twins↗

PubMed2001

Essential role of the nonreducing terminal alpha-mannosyl residues of the N-linked carbohydrate chain of bovine zona pellucida glycoproteins in sperm-egg binding.

It has been proposed that mammalian sperm bind species-specifically to carbohydrate chains of zona pellucida glycoproteins at fertilization. Although the sperm ligand carbohydrate chains have been characterized in mice and pigs, the existence of the ligands of other mammals remains unclear. In order to explore the bovine sperm ligand, two in vitro competition assay methods were applied. As a result, a high-mannose-type carbohydrate chain, Manalpha1-6(Manalpha1-3)Manalpha1-6(Manalpha1-3)Manbeta1-4GlcNAcbeta1-4GlcNAc, which is the major neutral chain in bovine egg zona glycoproteins, was shown to possess bovine sperm ligand activity. When nonreducing terminal alpha-mannosyl residues were eliminated from the zona glycoproteins by alpha-mannosidase digestion, the ligand activity was reduced, indicating that the alpha-mannosyl residues play an essential role in bovine sperm-egg binding. The number of sperm binding to eggs was reduced to about one-half after fertilization. The ligand-active high-mannose-type chain may be buried after fertilization, since its amount remains unchanged. Pretreatment of bovine sperm with the sperm ligand-carbohydrate chain significantly inhibited penetration of the sperm into oocyte and the male pronucleus formation. Thus, a correlation between the sperm ligand activity and in vitro fertilization rate was observed.

Animals↗

PubMed2001

The effect of interleukin-4 on the induction of intestinal mast cells and chronological cytokine profiles during intestinal nematode Strongyloides ratti infection.

The effect of interleukin-4 (IL-4) on the induction of intestinal mast cells and cytokine profiles during Strongyloides ratti infection was studied using IL-4 knockout (IL-4 KO) mice. The antigen-specific proliferative response of mesenteric lymph node cells was not impaired in IL-4 KO mice. The number of intestinal mast cells induced in IL-4 KO mice during S. ratti infection was 2- to 3-fold lower than that observed in WT mice. Intestinal mastocytosis had disappeared in IL-4 KO mice by day 21 postinfection, when significant mastocytosis continued to be observed in WT mice. In mesenteric lymphnode of IL-4 KO, IL-3 production decreased and mice IFN-gamma production significantly increased as compared with those of WT mice. The numbers of eggs excreted per gram of feces (EPG) by IL-4 KO mice were greater than those excreted by WT mice on day 6 postinfection, but no difference was observed in the subsequent period. In conclusion, intestinal mast cells are induced during S. ratti infection in the absence of IL-4, and IL-4 is not essential for protection against intestinal adult worms of S. ratti.

Animals↗

PubMed2001

IL-4 reduces resistance of mice to Trypanosoma cruzi infection.

The role of IL-4 has often been studied, especially in the Leishmania major infection model, but not in Trypanosoma cruzi infection. In the present study, the role of IL-4 in host defense against infection with the Tulahuen strain of T. cruzi was examined by depleting IL-4 with an anti-IL-4 monoclonal antibody in vivo. In both IL-4 depleted and control C57BL/6 mice, the parasitemia showed peaks on the 21st day of infection. Both parasitemia and mortality were decreased in IL-4 depleted mice compared with control mice when IFN-gamma and nitric oxide productions were increased in IL-4 depleted mice compared with control mice. The mice treated with N-nitro-L-arginine methyl ester, a competitive inhibitor of nitric oxide synthase, showed increased susceptibility to T. cruzi infection to the same level in both IL-4 depleted and control mice. Thus, it is suggested that endogenous IL-4 induces susceptibility to T. cruzi mainly by suppressing the production of IFN-gamma and nitric oxide, which has trypanocidal activity.

Animals↗

PubMed2001

Clinical and pedigree study on familial cases of West syndrome in Japan.

Nationwide survey on familial cases of West syndrome (WS) in first- and second-degree relatives was conducted by mailing a questionnaire to 64 major university hospitals, children's hospitals, and epilepsy centers in Japan, and by review of the Japanese cases in the literatures. Thirty-four familial cases, 20 males and 14 females, were obtained in 15 families including one with five affected members in two generations and another with three affected male siblings including a half brother by a different father (X-linked WS). A mother and the child or children were involved in three families. Nine families had 21 cryptogenic cases and six families had 13 symptomatic cases, and the etiologies were same among the affected members in each family. Familial cases of WS have characteristic clinical features and genetic mechanisms. Age of onset, seizure types, electroencephalographic abnormalities, early seizure outcome, effective treatment, long-term seizure prognosis, and long-term developmental prognosis were concordant among the affected members in each family. Long-term seizure and developmental prognoses were far better than those in WS in general, with seizure-free rate of 82% and normal mental development rate of 44%. Poor prognosis was limited to specific symptomatic cases. Adrenocorticotropic hormone (ACTH) was a treatment of choice, and even in relapse of WS after ACTH therapy, the patients well responded to antiepileptic drugs. Specific inheritance pattern was difficult to imagine in the majority of the present cases, except for one family with X-linked WS and another family with five patients of maternal inheritance. These results are helpful for the treatment choice and prognostication of clinical course for familial cases of WS.

Adrenocorticotropic Hormone↗

PubMed2001

WSX-1 is required for the initiation of Th1 responses and resistance to L. major infection.

WSX-1 is a class I cytokine receptor with homology to the IL-12 receptors. The physiological role of WSX-1, which is expressed mainly in T cells, was investigated in gene-targeted WSX-1-deficient mice. IFN-gamma production was reduced in isolated WSX-1(-/-) T cells subjected to primary stimulation in vitro to induce Th1 differentiation but was normal in fully differentiated and activated WSX-1(-/-) Th1 cells that had received secondary stimulation. WSX-1(-/-) mice were remarkably susceptible to Leishmania major infection, showing impaired IFN-gamma production early in the infection. However, IFN-gamma production during the later phases of the infection was not impaired in the knockout. WSX-1(-/-) mice also showed poorly differentiated granulomas with dispersed accumulations of mononuclear cells when infected with bacillus Calmette-Guerin (BCG). Thus, WSX-1 is essential for the initial mounting of Th1 responses but dispensable for their maintenance.

Animals↗

PubMed2001

Detection of kinetoplast DNA of Trypanosoma cruzi from dried feces of triatomine bugs by PCR.

It is important to clarify the distribution of infected triatomine bugs in the endemic area of Chagas' disease for proper control. In the present study, we tried to detect T. cruzi kinetoplast DNA by PCR from dried triatomine feces collected from the house wall of an endemic area to assess the distribution of infected bugs more easily. The primers (P35/P36) were chosen to amplify the conserved region within the minirepeats of T. cruzi kinetoplast minicircle DNA. The kinetoplast DNA of T. cruzi could be actually detected in the dried feces collected from the wall of a brick-built house in Santa Cruz, Bolivia. Next, we examined the stability of T. cruzi kinetoplast DNA in the feces exposed to artificial environments. T. cruzi DNA was also detected by PCR in the feces left for 26 weeks at 25 degrees C and in those left for 4 weeks at 40 degrees C. The present study indicates that examination of dried feces on the wall can be an effective tool for surveillance of the natural infection of triatomine bugs that live in houses.

Animals↗

PubMed2001

Biodisposition of FITC-labeled aloemannan in mice.

Biodisposition of FITC-labeled aloemannan (F-AM) with the homogenate from some organs in mice was demonstrated. F-AM was metabolized only by the mucosa from the large intestine into smaller molecules that were effectively absorbed in mice. The homogenate from the other tissues did not affect the metabolism of F-AM. The degraded product (1) of F-AM after incubation with 10% feces homogenate for 24 h was chromatographed on a highly porous polymer and a Sephadex LH-20 column to provide an FITC-degraded fraction (2), which was shown to have a molecular weight of 800 D on Sephadex G-25 gel permeation. Metabolite 2 was examined by physicochemical methods and shown to be a mixture of FITC-hexose and -2 hexose on FAB-MS. An FITC-degraded fraction (3) with a molecular weight of 3 KD was obtained by 6-h incubation with 10% feces homogenate on Sephadex G-25 column chromatography and was shown to be a mixture of FITC-9 and 12 x hexose on TOF-MS.

Adjuvants, Immunologic↗

PubMed2001

Serum immunosuppressive acidic protein as a potent prognostic factor for patients with metastatic renal cell carcinoma.

BACKGROUND: Estimation of survival probability of individual patients with metastatic renal cell carcinoma was difficult owing to diverse prognostic factors. We analyzed serum immunosuppressive acidic protein (IAP) levels and the cutoff value, then tested its validity for assessing patients' prognoses. METHODS: Serum IAP was measured longitudinally in 84 patients with metastatic disease. Before therapy, cutoff levels of IAP were tested every 20 microg/ml between 600 and 1200 microg/ml. The prognostic importance of IAP and its cutoff level was estimated. RESULTS: The cutoff level of IAP was set at 800 microg/ml for 40 patients who had metastatic disease with the primary tumor in situ and for 44 patients with recurrent disease. IAP was found to be a significant prognostic factor for both patient groups. CONCLUSIONS: Serum IAP is an important prognostic factor for patients with metastatic renal cell carcinoma. Stratification of patients according to prognosis is feasible using the cutoff level.

Adult↗

PubMed2001

Effect of KAD-1229, a nonsulfonylurea hypoglycemic agent, on plasma glucose and insulin in streptozotocin-induced diabetic dogs.

Hypoglycemic agents with a rapid onset and short duration of action should be useful for controlling postprandial hyperglycemia. Our aim was to establish a diabetes mellitus model in dogs, and then during an oral glucose tolerance test to compare the hypoglycemic effect and insulinotropic action of KAD-1229, a new hypoglycemic agent, with that of gliclazide, a conventional sulfonylurea. In this model, KAD-1229 reduced the increase in plasma glucose level without producing hypoglycemia. Gliclazide had a weaker effect on reduction of the glucose increase and caused hypoglycemia via a significantly raised insulin secretion in the late phase. A rapid insulinotropic action of KAD-1229 was clearly observed in the portal venous blood. The results suggest that in type 2 diabetes caused by, at least, insulin deficiency, KAD-1229 may improve impaired insulin secretion in the early phase and attenuate hyperglycemia without causing a sustained hypoglycemia.

Animals↗

PubMed2001

[A case of multiple sclerosis with recurrent episodes of psychiatric symptoms].

We reported a 19-year-old woman with multiple sclerosis (MS) with recurrent episodes of psychiatric symptoms at the age of 10 and 19, as the first and 11th relapse, respectively. Her first episode of MS resembled acute encephalitis at the age of 9 and she relapsed 12 times. The psychiatric symptoms were not mood disorders but altered states of consciousness, such as the delirous state. She was treated with high doses of intravenous methylpredonisolone and her symptoms were almost resolved, but her anxiety neurosis remained. Her MRI showed demyelination in the white matter of the frontal lobe and the hippocampus, which suggested that psychiatric symptoms of MS would be related to the frontal lobe lesion.

Adult↗

PubMed2001

[A clinicopathological evaluation of prognostic factors of urothelial tumors of the renal pelvis and ureter].

We investigated the clinicopathological features of 109 patients with urothelial tumors of the renal pelvis and ureter who underwent surgery at four institute from April, 1975 to September, 1997. The patients consisted of 71 males and 38 females, and the mean age was 66.8 years, ranging from 41 to 92 years. Mean followup period was 43 months. The prognostic significance of the pathological factors; pT, Grade, INF, tumor size, pL, pV and pN were evaluated. All these factors affected the survival rates significantly in univariate analysis. Multivariate analysis showed the most influential prognostic factors to be pT and pN.

Adult↗

PubMed2000

Two circadian oscillatory mechanisms in the mammalian retina.

To investigate the mechanism that controls circadian rhythms in the mammalian retina, we examined the mRNA expression rhythms of serotonin N-acetyltransferase (NAT), the mammalian clock gene rPer2 and a clock-controlled gene Dbp in the retina of rats with lesions of the suprachiasmatic nucleus (SCN), the master clock in mammals. Northern blot analyses showed that retinal NAT mRNA still exhibited the circadian expression in the SCN-lesioned rats, whereas the lesion abolished the rhythms of rPer2 and Dbp mRNAs. These findings suggest that the mammalian retina has two circadian oscillatory mechanisms: one can generate rhythmicity independent of the SCN and the other requires the SCN to maintain circadian oscillation.

Animals↗

PubMed2000

Urethral obstruction in patients with nighttime wetting: urodynamic evaluation and outcome of surgical incision.

The aim of this study was to investigate urodynamic findings and the outcome of surgical incision in patients with nighttime wetting due to urethral obstruction. A total of 239 patients with nighttime wetting (157 males and 82 females; mean age, 8.7; range, 4-18 years) was studied. One hundred and ten patients had monosymptomatic enuresis alone and 129 both nighttime wetting and daytime symptoms, that is, the majority was not simple bedwetters, but had signs of bladder overactivity. All patients were first treated with bladder training and fluid intake after dinner was restricted. The non-responders were then treated with tricyclic antidepressants, anticholinergics, or intra-nasal desmopressin and conditioning therapy. Ninety-seven patients who did not respond to these conventional treatments were investigated by voiding cystourethrography, bougie à boule, and urodynamic study. Urethral obstruction was noted in 34 patients (14.2%); posterior urethral valves in three males, ring stricture of the bulbar urethra in 26 males and distal urethral stenosis in five females. Detrusor instability was noted in 30 (94%) of 32 patients. Three patients had <15 mL/s of maximum flow rate and none had post-void residual urine. Pressure at maximum flow (PQ(max)) was 106.5 +/- 26.3 cm H(2)O in pressure/flow study. After surgery, nighttime wetting was cured in 25 patients (73.5%), improved in four (11.8%). Detrusor instability disappeared in six of 16 patients studied (37.5%) and improved in 8 (50%), and PQ(max) decreased significantly after operation (P = 0. 0034). In conclusion, most of the patients with urethral obstruction have detrusor instability and high pressure voiding, and these conditions improved after operation.

Adolescent↗

PubMed2000

Analysis of loss of heterozygosity at 16p12-p13 (familial neuroblastoma locus) in 470 neuroblastomas including both sporadic and mass screening tumors.

BACKGROUND: Neuroblastoma (NBL) in children usually occurs in a sporadic form. However, it rarely occurs in families. Recently, the familial neuroblastoma (FNB) locus has been mapped to 16p12-p13 by linkage analysis. PROCEDURE: Here we show the result of loss of heterozygosity in the region spanning 16p12-p13 (D16S406-D16S409, 46 cM) in 470 NBLs including both sporadic and mass screening cases. RESULTS: Allelic loss was found in 61(13%) tumors. Deletion of 16p was associated with mass screening tumor (P = 0.035) and <1 year of age at diagnosis (P = 0.048). We found two commonly deleted regions: the sizes of the region were approximately 2 cM and approximately 6 cM. CONCLUSIONS: Our data suggested that allelic loss of 16p was common in favorable NBLs, and there may be at least two candidate loci within the region of FNB.

Child↗

PubMed2000

The crucial role of granulocytes in the early host defense against Strongyloides ratti infection in mice.

The involvement of granulocytes in the host early defense against the nematode, Strongyloides ratti, was studied. It was confirmed that granulocytes were effectively depleted for 4 days by anti-granulocyte monoclonal antibody (anti-Gr-1). To examine the involvement of granulocytes in the host defense against migrating larvae, 2,000 S. ratti infective larvae (L3) were inoculated subcutaneously 1 day after antibody treatment. The number of S. ratti eggs secreted in feces (EPG) was higher in the granulocyte-depleted group than in the control group. The number of migrating larvae also increased in the granulocyte-depleted group in accordance with the increase in EPG. Therefore granulocytes are crucial for the host early defense against migrating larvae of S. ratti. Next, the involvement of granulocytes in the intestinal early defense was examined. Mice were treated with the antibody on day 3 post-infection. On that day, almost all inoculated larvae reached the intestine and molted to become adults. EPG on day 5 post-infection was increased by the antibody treatment, but no effect was observed on intestinal worm numbers. The fecundity (EPG/worm number) of S. ratti adult worms in the granulocyte-depleted group was higher than that in the control group. Thus granulocytes are also involved in the intestinal early defense through suppressing fecundity of the adult worms. On the other hand, the depletion of granulocytes had no effect on the late adaptive response against S. ratti adult worms (e.g. number of intestinal mucosal mast cells, time of worm expulsion). These results suggest that granulocytes are mainly involved in the host early defense against parasites.

Animals↗