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Biomedical subjects

T Sakamoto

Publications and source records attributed to T Sakamoto.

At least 199 records · Page 11Linked to original sources
PubMed2000

Formation of platelet aggregates after attacks of coronary spastic angina pectoris.

Using a novel laser-light scattering method, we examined platelet aggregability, especially small-sized platelet aggregates, at baseline and after spontaneous coronary spastic attacks in 14 patients with coronary spastic angina, and before and after anginal attacks during an exercise test in 11 patients with stable exertional angina. The number of small-sized platelet aggregates after coronary spastic anginal attacks increased significantly, but not in patients with stable exertional angina. These results imply that an increase in the number of small-sized platelet aggregates from coronary spasm may be a trigger for coronary thrombosis via medium- and large-sized platelet aggregates.

Acetylcholine↗
PubMed2000

Vergence disorders in patients with spinocerebellar ataxia 3/Machado-Joseph disease: a synoptophore study.

Diplopia, a common symptom in spinocerebellar ataxia 3/Machado-Joseph disease (SCA3/MJD) cases, is not always due to asymmetric ophthalmoplegia. We found a Japanese SCA3/MJD family, in which three patients clearly had an impairment of divergence eye movement. We thus quantitatively examined the vergence ranges in eight Japanese SCA3/MJD cases using the synoptophore test. An impairment of the vergence eye movements was found in all patients, and the vergence impairment pattern, but not the ophthalmoplegia pattern, was found to be compatible with the diplopia pattern. The diplopia in SCA3/MJD cases is, therefore, attributed, at least in part, to the impairment of the vergence eye movements.

Abducens Nerve↗
PubMed2000

Comparison of the risk factors for coronary artery spasm with those for organic stenosis in a Japanese population: role of cigarette smoking.

We compared the risk factors for coronary spasm with those for coronary atherosclerosis in 183 patients with coronary spasm, 132 patients with coronary organic stenosis, and 224 control subjects with chest pain syndrome. Our findings confirmed that, when compared with controls, age, gender, total cholesterol, LDL-cholesterol, hypertension, diabetes mellitus, and cigarette smoking are all significant risk factors for coronary organic stenosis. On the other hand, only cigarette smoking proved to be a significant risk factor for coronary spasm. Also, when compared between coronary spasm group and coronary organic stenosis group, the incidence of cigarette smoking in males was significantly higher in the coronary spasm group than in the coronary organic stenosis group. We conclude that cigarette smoking is a crucial risk factor for coronary spasm. On the other hand, serum lipid levels and the incidence of hypertension and diabetes mellitus were within the normal ranges in the coronary spasm patients and were thus poorly associated with coronary spasm. These results showed that the risk factors for coronary spasm differ significantly from those for atherosclerosis-based coronary stenosis in the Japanese. Among the risk factors for coronary atherosclerosis (organic stenosis) smoking alone was a significant preventable risk factor for coronary artery spasm.

Aged↗
PubMed2000

Difference in fibrinolytic activity between multivessel coronary spasm and one-vessel coronary spasm.

Plasminogen activator inhibitor activity was higher in 18 patients with multivessel spasm than in 20 patients with 1-vessel spasm and in 22 control patients. Tissue plasminogen activator antigen was also higher in patients with multivessel spasm than in those with 1-vessel spasm and control patients. The increased plasminogen activator inhibitor activity in patients with multivessel spasm indicates that the fibrinolytic system is more impaired in such patients than in those with 1-vessel coronary spasm; this may be related to the higher incidence of refractory angina during hospitalization and cardiac events during the follow-up period.

Angina Pectoris↗
PubMed2000

A soluble transforming growth factor beta receptor expressed in muscle prevents liver fibrogenesis and dysfunction in rats.

We demonstrated that local expression of a dominant-negative type II TGF-beta receptor prevents live fibrogenesis and dysfunction in dimethylnitrosamine-treated rats. Using the same model, we have now tested whether a soluble TGF-beta receptor expressed in skeletal muscle can effectively suppress TGF-beta signaling in a remote organ (the liver). We constructed an adenovirus expressing an entire ectodomain of human TGF-beta type II receptor fused to the Fc portion of human IgG (AdTbeta-ExR). This soluble receptor secreted from AdTbeta-ExR-infected cells bound TGF-beta and blocked TGF-beta-signaling in vitro. After intramuscular injection of AdTbeta-ExR in rats, the soluble receptor protein was detectable in the blood for at least 3 weeks. When such rats were treated with dimethylnitrosamine, liver fibrosis was markedly attenuated without apparent systemic or local side effects. The hepatic hydroxyproline content was reduced to a level indistinguishable from that achieved by local expression of the dominant-negative TGF-beta receptor. Since a qualitatively and quantitatively similar suppression was achieved by the two methods, it may be concluded that the new strategy can achieve a complete inhibition of TGF-beta signaling under pathophysiological conditions in vivo. This strategy should facilitate clarification of the role of TGF-beta in vivo in various organs where direct gene transfer seems to be difficult.

Animals↗
PubMed2000

The effect of interleukin-6 (IL-6)/gp130 signalling on biliary epithelial cell growth, in vitro.

The effect of IL-6 on the growth of mouse biliary epithelial cells (BEC), in vitro, was tested by comparing BEC obtained IL-6-deficient mice (IL-6(-/-)) to wild-type littermate controls (IL-6(+/+)), in two different media: simple serum-free media (S-SFM), and complete serum-free media (C-SFM) containing forskolin, which stimulates BEC IL-6 production. In S-SFM, neither IL-6(+/+)nor IL-6(-/-)BEC constitutively produced IL-6 mRNA or protein, and there was no difference between IL-6(+/+)and IL-6(-/-)BEC growth. In contrast, when the BEC were maintained in C-SFM, over 48 h, the growth of IL-6(+/+)BEC was 40% greater than IL-6(-/-)BEC (P<0.006). Enhanced IL-6(+/+)BEC growth in C-SFM was associated with induced expression of IL-6 mRNA and IL-6 protein secretion into the medium, upregulation of the IL-6Ralpha (gp80) and phosphorylation of the signal transducing molecule gp130. In C-SFM, anti-IL-6 neutralizing antibodies blocked enhanced IL-6(+/+)BEC growth, whereas exogenous rhIL-6 stimulated retarded growth of IL-6(-/-)BEC. Thus, under conditions that mimic an inflammatory or stressful microenvironment in vivo, BEC produce, secrete and respond to IL-6, via upregulation and activation of the IL-6Ralpha (gp80)/gp130 signaling system in an autocrine/paracrine manner.

Animals↗
PubMed2000

Prognostic significance of vascular endothelial growth factor and its receptors in endometrial carcinoma.

OBJECTIVE: The aim of this study has been to evaluate the clinical significance of expression of VEGF and its receptors, Flt-1, KDR, and Flt-4, in endometrial carcinomas. METHODS: Specimens of endometrial carcinomas from 86 patients were investigated immunohistochemically using respective specific antibodies. Additionally, samples from 14 patients with complex atypical endometrial hyperplasia (AEH) and 15 patients with normal endometria were also examined. Immunohistochemical assessment was classified as negative, weakly positive, and strongly positive according to staining intensity and the percentage of positive cells. RESULTS: In positive cases, VEGF and its receptors were usually expressed homogeneously in the cytoplasms of cells in the endometrial carcimona, similar to the staining intensity of endothelial cells of stromal microvessels adjacent to carcinoma nests. The overall positive rates in the 86 carcinoma specimens were 66% for VEGF, 51% for Flt-1, 38% for KDR, and 57% for Flt-4. Their expressions in endometrial carcinoma tissues were high with significance or with borderline significance, compared to those in samples of complex AEH or normal endometria. Survival curves determined by the Kaplan-Meier method and univariate analysis showed VEGF, Flt-1, and Flt-4 overexpression to be related to poor prognosis of patients with endometrial carcinomas. However, multivariate analysis revealed that Flt-4 overexpression correlated independently with poor survival, similar to a value for myometrial invasion at one-half or more and that for retroperitoneal lymph node metastasis, whereas VEGF and Flt-1 overexpression did not. CONCLUSION: Flt-4 overexpression might be a promising prognostic indicator for survival of a patient with endometrial carcinoma.

Adult↗
PubMed2000

Reduction of blood loss using tranexamic acid in total knee and hip arthroplasties.

There have been several attempts to reduce postoperative blood loss in patients undergoing total arthroplasty. Benoni et al. reported the usefulness of tranexamic acid in total knee arthroplasty (TKA). We investigated its effect in TKA and total hip arthroplasty (THA). Blood loss was significantly reduced in patients given tranexamic acid in both the TKA and THA groups, and no severe complications, such as venous or pulmonary thrombosis, were noted in any of the patients who received the agent. Administration of tranexamic acid seems to be useful for reducing postoperative blood loss in TKA and THA.

Antifibrinolytic Agents↗
PubMed2000

The fertility and pregnancy outcomes of the patients who underwent preservative operation followed by adjuvant chemotherapy for malignant ovarian tumors.

The fertility and pregnancy outcomes of the patients were studied, who previously underwent preservative operation for malignant tumors, including those of borderline malignancy, in our ward from 1981 to 1995. For each of the 9 patients, unilateral ovary was preserved, the range of their ages before operation was 10 to 28 years old, and histologically, 7 patients had tumors derived from germ cells, and 2 had those from epithelial cells. As for clinical stages according to the FIGO's criteria, 5, 1, 2 and 1 patients were in stage I, II, III and IV, respectively. The regimens of the combination chemotherapy for patients with germ cell tumors were PVB (cisplatin, vinblastine and bleomycin), PEP (cisplatin, etopside and pepleomycin), PVP (cisplatin, vinblastine and pepleomycin), AVAC (doxorubicin, vincristine, actinomycin-d and cyclophosphamide). Those for the patient with epithelial tumors were CAP (cyclophosphamide, doxorubicin and cisplatin), CP (cyclophosphamide and cisplatin). Eight patients have been doing well, although 1 of them experienced recurrence and died. Amenorrheic periods of 2 to 12 months were noticed in 3 patients, although in all of them, ovulatory cycles recovered. Eight pregnancies were reported: 5 term delivery with normal babies, and others were preterm termination due to abruptio placenta with a baby of appropriate for date, spontaneous abortion, and artificial termination. We suppose that the combination chemotherapy applied for the patients in the present study affected neither the fertility of the patients nor the outcomes of the pregnancies.

Adolescent↗
PubMed2000

Secondary acute nonlymphocytic leukemia following successful chemotherapy combining cisplatin, doxorubicin, and cyclophosphamide for stage IV epithelial ovarian cancer.

Although chemotherapy is indispensable for the treatment of ovarian cancer, secondary acute leukemia has become increasingly important as one of the most unfavorable late effects according to widespread long-term chemotherapy. We report a patient suffering from acute nonlymphocytic leukemia (ANLL) 3 years after treatment for stage IV ovarian cancer began.

Antibiotics, Antineoplastic↗
PubMed2000

Clinical features of sudden hearing loss associated with a high signal in the labyrinth on unenhanced T1-weighted magnetic resonance imaging.

We report on five patients with high signals in the labyrinth on unenhanced magnetic resonance imaging who developed sudden hearing loss and vertigo. Weissman et al. (1992) suggested the possibility that such high signals were caused by hemorrhage. We assessed these patients using audiograms, caloric tests, and auditory brainstem responses to investigate the possibility of inner ear hemorrhage. Most of the patients were found to have severe and irreversible impairment of both cochlear and vestibular function. These findings were consistent with the hypothesis that their symptoms were caused by inner ear hemorrhage.

Adolescent↗
PubMed2000

Ebselen decreases ozone-induced pulmonary inflammation in rats.

We studied the effects of ebselen on rat lung inflammatory responses against ozone exposure. Rats were treated with ebselen every 12 h from 1 h before a single 4-h exposure to 2 ppm ozone. Treatment with ebselen (10 mg/kg) significantly decreased pulmonary inflammation as indicated by the albumin concentration and the number of neutrophils in the bronchoalveolar lavage fluid 18 h after the ozone exposure. Although treatment with ebselen did not alter the macrophage expression of inducible nitric oxide synthase after the ozone exposure, it did markedly inhibit the nitration reaction of tyrosine residues, suggesting that ebselen scavenges peroxynitrite during ozone-induced pulmonary inflammation. Treatment with ebselen also enhanced the pulmonary expression of both copper, zinc, and manganous superoxide dismutases at the same time point. These enzymes may also contribute to a decrease in the formation of peroxynitrite by lowering the concentration of superoxide. Thus, ebselen represents a useful compound for protecting against certain acute lung injuries by modulating the oxidant-related inflammatory process.

Acute Disease↗
PubMed2000

Experimental study of an artificial esophagus using a collagen sponge, a latissimus dorsi muscle flap, and split-thickness skin.

The time and effort spent trying to devise an artificial esophagus have not yet resulted in success, and leakage and strictures at the anastomotic sites remain the most frequent complications. We developed an artificial esophagus with a bilayered structure made of porous collagen sponge (artificial dermis; AD), a latissimus dorsi muscle flap (LD), and split-thickness skin (STS). We investigated whether the use of AD prevented the contraction of grafted skin and its effects on the extensibility of the neoesophagus in rabbits. We experimented with two groups. In the AD group, AD was applied to the surface of the LD. Three weeks later, the STS was grafted. In the control group, the STS was grafted directly onto the LD. The sizes of the STS in both groups 3 weeks after the graft were, respectively, 56.6% +/- 4.1% and 39.0% +/- 10.2% of the initial surface area of the STS (P < 0.01). The roll made in the AD group had better extensibility than that in the control group. We replaced the cervical esophagus in 12 rabbits with the neoesophagus made from AD, STS, and LD. The longest survival period was 16 days. Esophagography did not reveal either anastomotic leakage or stenosis in any of the five rabbits in the experiments. These findings suggested that AD can thus be used to create a more suitable hybrid artificial esophagus.

Animals↗
PubMed2000

The development and compensation of biliary cirrhosis in interleukin-6-deficient mice.

In an effort to understand the role of IL-6/gp130 signaling in chronic liver injury, IL-6 deficient (IL-6(-/-)) and wild-type control (IL-6(+/+)) mice were subjected to bile duct ligation (BDL) for 12 weeks. This maneuver causes chronic biomechanical stress and liver injury, fueling sustained biliary epithelial and hepatocyte proliferation. By 12 weeks after BDL, IL-6(-/-) mice develop significantly higher total serum bilirubin levels (23.2 +/- 2.3 versus 14.9 +/- 2.1 mg/dl, P < 0.0001; delta bilirubin subfraction 16.7 +/- 4.0% versus 9.2 +/- 1.8%; P < 0.002), and the majority (15/18) show "black" gallbladder bile, compared to IL-6(+/+) mice (5/16; P < 0.003). The IL-6(-/-) mice also cannot sustain the compensatory liver mass increase commonly seen with chronic obstructive cholangiopathy, because of less hepatocyte proliferation, despite a rate of hepatocyte apoptosis similar to that of IL-6(+/+) mice. Moreover, IL-6(-/-) mice show a more advanced stage of biliary fibrosis and a higher mortality rate than the IL-6(+/+) controls (51% versus 23%; P < 0.02). These phenotypic changes in the IL-6(-/-) mice are associated with decreased expression and phosphorylation of gp130 and the transcription factor STAT3, compared to IL-6(+/+) mice. Daily treatment with exogenous recombinant IL-6 for 3-6 weeks starting at 6 weeks after BDL significantly lowers the serum total bilirubin in both groups. In the IL-6(-/-) mice, exogenous IL-6 treatment also increases the level of gp130 protein expression and completely reverses the loss of liver mass by increasing the hepatocyte proliferation. In conclusion, IL-6 appears to contribute to biliary tree integrity and maintenance of hepatocyte mass during chronic injury.

Alanine Transaminase↗
PubMed2000

Brain distribution of 6-mercaptopurine is regulated by the efflux transport system in the blood-brain barrier.

6-mercaptopurine (6-MP) has been used clinically for 40 years to maintain remission in patients with acute lymphoblastic leukemia (ALL). However, central nervous system (CNS) relapses frequently occur in patients with ALL who continuously receive anticancer drugs, including 6-MP, during remission maintenance therapy. The cause of such CNS relapse is not well understood. One possible reason may involve the restricted distribution of 6-MP in the brain. This study, therefore, investigates the blood-brain barrier (BBB) transport which largely regulates 6-MP distribution in the brain using a quantitative microdialysis technique and centers on the efflux transport of 6-MP across the BBB. The brain tissue, cerebrospinal fluid (CSF), or hippocampal interstitial fluid (ISF) concentration of 6-MP was very low compared with the unbound plasma concentration, suggesting that 6-MP distribution in the brain is highly restricted. Kinetic analyses of this BBB transport showed that the efflux clearance from brain ISF to plasma across the BBB (CLout) is approximately 20-times greater than the influx clearance from plasma to brain (CLin). The CLout was significantly reduced by 1mM N-ethylmaleimide (NEM), a sulfhydryl-modifying agent, suggesting the participation of transport protein in the efflux of 6-MP across the BBB. In addition, efflux transport was inhibited by an intracerebral infusion of probenecid (1.5 mM), p-aminohippuric acid (PAH, 3.0 mM), benzoate (3.6 mM), or salicylate (3.7 mM) administered through a microdialysis probe, but neither choline (0.8 mM) nor tetraethylammonium (TEA, 0.7 mM) had any effect. These data suggest that the restricted 6-MP brain distribution may be ascribed to efficient efflux from the brain, possibly via both the organic anion transport system, shared with probenecid and PAH, and the monocarboxylic acid transport system, shared with benzoate and salicylate.

Animals↗
PubMed2000

Is emergency open chest cardiopulmonary resuscitation accepted by patients' families?

Emergency open chest cardiopulmonary resuscitation (OCCPR) is sometimes performed on patients with cardiopulmonary arrest (CPA), especially those resulting from trauma. Since OCCPR is frequently carried out without the permission of patients' families, we surveyed the opinions of the families. A total of 1058 CPA patients were transferred to our department during the last 15 years. We sent questionnaires individually to the families of these patients to ask their opinions about OCCPR. The questionnaire provided the six questions allowing multiple answers; (1) Do you unconditionally agree with OCCPR? (2) Do you agree with OCCPR in children? (3) Do you agree with OCCPR in elderly patients? (4) Do you agree with OCCPR without permission from patient's families? (5) Do you entrust OCCPR to the doctors in charge? and (6) others. The questionnaire reached 846 families, of which 277 (32.7%) responded. The percentage response to each question was (1) 70.2, (2) 5.8, (3) 21.8, (4) 7.1, (5) 4.2 and (6) 5.0%. The younger the age of the responders the more they agreed with OCCPR. All the responders less than 30 years old agreed with the procedure. Of the 277 families, 95 had CPA patients treated with OCCPR. This group of families responded to six questions at the following rates: (1) 79.5, (2) 6.0, (3) 13.3, (4) 2. 4, (5) 4.8 and (6) 4.8%, suggesting that families with OCCPR patients are more cooperative to our treatment than those with non-OCCPR patients. The results of this study suggest that OCCPR in CPA patients is generally accepted by the patients' families, especially by young generations, although post-OCCPR careful explanation to patients' families is still indispensable.

Adult↗