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Biomedical subjects

Y Sakai

Publications and source records attributed to Y Sakai.

At least 325 records · Page 18Linked to original sources

[Outcome of emergency surgery for Stanford type A aneurysms: selection of operative procedures and supported systems of cerebral protection].

Fourteen surgical cases of acute dissecting aneurysms of Stanford type A were reported. Clinical symptoms, operative methods, pathophysiology, cerebral protection, supported systems, and prognosis were examined. All patients underwent surgery within 5 days of symptom onset. The patient population consisted 8 males and 6 females with a mean age of 56.6 years. Ascending aortic replacement was performed using a vascular graft 12 patients. ECC was performed under deep hypothermia. Femoral artery cannulation and retrograde cerebral perfusions was performed in all cases. The ascending aorta was the site of entry in 13 of the 14 cases. Whenever feasible, enhanced CT and aortography were performed to confirm the entry lesion. Two patients expired. One patient died intraoperatively due to massive bleeding. The other patient, while hospitalized, experienced a cerebrovascular accident and died due to pneumonia. All other patients ran an uneventful post-operative course without cerebrovascular accident. In conclusion we think that although ascending aorta replacement using prosthetic grafts is not ideal for patients with Stanford type A dissecting aneurysms, it is a viable option for emergency cases. We found retrograde circulatory cerebroplegia (RCCP) to be satisfactory for brain protection during these emergency procedures.

Adult↗

[Development of non-iodized oily agent in targeting chemoembolization for hepatocellular carcinoma].

The purpose of this study was to evaluate a new oily agent in targeting chemoembilization for hepatocellular carcinoma. The oily preparation was made by mixing non-iodinated poppy seed oil and a thickener to obtain the same viscosity as Lipiodol. The oily preparation and Lipiodol were compared by injecting them into the hepatic artery of rabbits inoculated with VX 2 carcinoma in their liver. On the CT scan following intra-arterial injection, tumors were visibly stained in the non-iodinated preparation group, whereas the Lipiodol group was not evaluable because of excessively high attenuation. The non-iodinated oily preparation was concluded to be of clinical significance.

Animals↗

[Inflammatory response during cardiopulmonary bypass: neutrophil apoptosis].

Cardiopulmonary bypass (CPB) is essential to open heart surgery. However, CPB induces many types of inflammatory response, and may contribute to the tissue injury and the development of postoperative complications. On the other hand, the neutrophil responses to injury and infection immediately and secretes elastases and cytokines followed by prolongation of inflammatory changes, and programmed cell death (apoptosis) of neutrophils is delayed by inflammatory response. In this study, we evaluated the alternation of the neutrophil life span during CPB. Peripheral blood was obtained from eight adult patients before CPB, 1 hr and 2 hr after CPB start. After separation of neutrophils, and incuvation in the presence of TNF-alpha for 3 hr, we measured fluorescence-microscopically apoptosis rate (%A). %A significantly decreased with time (before 9.7 +/- 2.3%, 1 hr 3.0 +/- 1.0%, 2 hr 1.5 +/- 0.6%, p < 0.05). We conclude that neutrophil apoptosis was suppressed significantly during CPB. Systemic inflammatory change induced by CPB may be prolonged with extended life span of neutrophil.

Adult↗

[The investigation of surgical procedures for post infarcted ventricular septal defects: a comparison between Daggett and David method].

Post infarcted ventricular septal perforations (VSP) has diverse clinical and pathological manifestations and the surgical results in severe cases have not yet been satisfactory. In the past we had performed the procedure of Daggett. However since 1992 we have also introduced the procedure of infarction exclusion technique proposed by David which involves plastering the ventricular cavity in a large patch without infarcted myotomy. We reported 5 cases treated with David method, 5 cases with Daggett method, and their results were compared. There were four mortality cases in Daggett method and three in David method. No significant difference was observed regarding the surgical mortality. However, there were different post-operative features between the two groups. In Daggett method patients had prolonged heart failure and LOS. In David method patients, had no severe LOS, but residual shunt were recognized in two cases. We think that the emergence of residual shunt in David method was probably due to suturing without prior removal of the damaged fragile infarcted myocardium. In Daggett method there were death cases caused by LOS and postoperative heart failure but without residual shunts. Despite its recent growing popularity for treating VSP, our experience suggests that residual shunt is an important issue remains to be solved in David method.

Aged↗

Comparison of the antiplatelet effect of YM337 and abciximab in rhesus monkeys.

We directly compared the effects of YM337, the Fab fragment of the humanized monoclonal antibody C4G1, on platelet aggregation and template bleeding time with those of abciximab, the Fab fragment of the human/murine chimeric monoclonal antibody 7E3, in rhesus monkeys. The duration of inhibition of platelet aggregation by abciximab after i.v. bolus injection was much longer than that by YM337. Although YM337 significantly prolonged template bleeding time at 5 min after i.v. bolus injection, this action recovered within 1 h after injection. In contrast, although abciximab also prolonged template bleeding time, the duration of this effect was sustained. In a dose-escalating continuous infusion study, we evaluated the relationship between inhibition of platelet aggregation and prolongation of template bleeding time. Platelet aggregation was inhibited by over 80% by both agents at 3 microg/kg per min, and template bleeding time was prolonged to about 30 min at 30 microg/kg per min for YM337 and 10 microg/kg per min for abciximab. Interestingly, plasma concentrations between inhibition of platelet aggregation and prolongation of template bleeding time did not overlap with YM337, but did overlap with abciximab. These results suggest that YM337 allows easier control of antiplatelet activity with less effect on bleeding time than abciximab, and has a wider therapeutic window than abciximab.

Abciximab↗

Isolation and characterization of Xenopus laevis xSox-B1 cDNA.

A family of genes related to the sex-determining region Y gene (SRY) has been termed SOX, and the members are known to encode transcriptional factors and be involved in animal development. We have isolated and sequenced a novel Sox cDNA of Xenopus laevis in this study. The cDNA encodes a protein of 309 amino acids, which encompasses a B-type SOX HMG box; the cDNA was named xSox-B1 in this study. The xSox-B1 mRNA is 1.6 kb in length. Various tissues of adult frog were tested for xSox-B1 mRNA by reverse transcription/ polymerase chain reaction, and the results showed that xSox-B1 expression was highly restricted to the ovary. The message of the xSox-B1 gene was also detected in unfertilized eggs and the late blastula embryos of X. laevis. Recombinant polypeptide of the xSox-B1 HMG domain preferentially binds to the AACAAT sequence.

Amino Acid Sequence↗

XLS13A and XLS13B: SRY-related genes of Xenopus laevis.

SRY-related cDNAs, XLS13A and XLS13B, have been isolated from Xenopus laevis ovary. The cDNAs encode polypeptides of 382 and 375 amino acids, respectively. Nucleotide sequences of the two cDNAs are highly homologous to each other. The type-A and type-B XLS13 proteins, and xSox13 reported previously share an identical high mobility group (HMG) box at the amino acid level, although they contain silent nucleotide alterations. The HMG box exhibits strong similarity (> 93% amino acid identity) to those of mouse Sox4/human SOX4 and chicken Sox11/human SOX11. The size of XLS13A/XLS13B mRNA was estimated to be 2.8 knt in Xenopus ovary by Northern analysis. Reverse transcription/polymerase chain reaction (RT/PCR) assay indicated that XLS13A and XLS13B mRNAs are present in various tissues of adult frog. The mRNAs of XLS13A and XLS13B of maternal origin found in unfertilized eggs disappear in the early stages of the Xenopus embryo. DNA-binding properties of the XLS13 HMG domain were examined by electrophoretic mobility shift assay (EMSA). The HMG domain preferentially binds to the canonical target sequence of SOX proteins, AACAAT, in vitro.

Amino Acid Sequence↗

The paramyxovirus, Sendai virus, V protein encodes a luxury function required for viral pathogenesis.

The Sendai virus (SeV) V protein is characterized by the unique cysteine-rich domain in its carboxy-terminal half which is fused to the amino-terminal half of the P protein, but its function has remained enigmatic. The V protein-directing mRNA is generated by a remarkable process known as mRNA editing involving the pseudotemplated addition of a single G residue at a specific septinucleotide locus in the P gene, whereas the unedited exact copy encodes the P protein. Here, we introduced two nucleotide changes in the septinucleotide motif (UUUUCCC to UUCUUCC) in a full-length SeV cDNA and were able to recover a virus from the cDNA, which was devoid of mRNA editing and hence unable to synthesize the V protein. Compared with the parental wild-type virus with regard to gene expression, replication and cytopathogenicity in various cell lines in vitro, the V(-) virus was found to be either potentiated or comparable but never attenuated. The V(-) virus, however, showed markedly attenuated in vivo replication capacity in and pathogenicity for mice. Thus, though categorized as a nonessential gene product, SeV V protein encodes a luxury function required for in vivo pathogenicity.

Animals↗

Assessment of the longevity of the liver using a rat transplant model.

To assess the longevity of the liver, arterialized, orthotopic liver grafts were performed using syngeneic male BN/BiRij rats. Young (5-month-old) livers were transplanted into 5-month-old recipients (group I, n = 27), and old (28-month-old) livers were transplanted into 5-month-old rats (group II, n = 28). Recipient survival after transplantation was similar in both groups. The average age of the livers at the time of death was 16.7 months in group I and 39.1 months in group II. Four of the livers in group II survived for more than 4 years (48.1 to 52.4 months). Early deaths (less than 1 year) after transplantation were most commonly caused by biliary obstruction and cholangitis in both groups. Late deaths (more than 1 year) after grafting were mainly from heart failure or tumors. None of the animals died of liver failure or liver disease. Weight gain in the rats, total serum protein levels, and alanine transaminase levels after transplantation did not differ significantly between the two groups. There was a trend for the histological features of aging of the liver-fibrosis, bile duct proliferation, and pigment deposition-to become more prevalent as the livers became very old (mean age, 46 months). Nevertheless, typical aging changes, as individual findings, were absent in nearly half of the oldest organs. The alterations in morphology had no apparent effect on the ability of the livers to sustain the lives of the recipients. The liver of the BN/BiRij rat was capable of surviving far beyond the maximum life span of BN/BiRij rats, and rats in general. It did not become diseased in the process.

Age Factors↗

Ischemic stricture of the rectosigmoid colon caused by division of the superior rectal artery below Sudeck's point during sigmoidectomy: report of a case.

Despite Sudeck's cautionary report regarding the risk of colon necrosis following a pull-through procedure, published in 1907, most colorectal surgeons do not pay close attention to Sudeck's critical point when operating in the rectosigmoid region. We report herein the case of a patient who developed an ischemic stricture, 6 cm in length, in the rectosigmoid colon distal to the anastomosis following a radical sigmoidectomy with division of the superior rectal artery immediately distal to Sudeck's point. This is the first documentation of a patient developing an ischemic stricture attributable to sigmoidectomy. Division of the artery distal to Sudeck's point most probably impaired the blood supply to the rectosigmoid colon, which subsequently resulted in occlusive ischemic colitis. Thus, there is a risk that division of the superior rectal artery distal to Sudeck's point may lead to colonic ischemia in the remaining rectosigmoid region following sigmoidectomy.

Aged↗

Induction of apoptosis in a human hepatocellular carcinoma cell line by a neutralizing antibody to transforming growth factor-alpha.

A cell line derived from a Japanese man with hepatocellular carcinoma was established in culture and designated OCUH-16. The cell line has the morphological and chromosomal features of hepatocellular carcinoma cells and has a short doubling time (approximately 33 h). OCUH-16 cells were shown to express transforming growth factor-alpha (TGF-alpha) in addition to albumin, DNA polymerase-alpha, c-JUN, and the retinoblastoma gene product. Electron microscopy revealed TGF-alpha immunoreactivity associated with the cell membrane, but TGF-alpha was not detected in medium conditioned by OCUH-16 cells by enzyme-linked immunosorbent assay. Reverse transcription and polymerase chain reaction analysis revealed the presence of TGF-alpha messenger RNA in these cells. Culture of OCUH-16 cells in the presence of a neutralizing antibody to TGF-alpha inhibited cell proliferation and induced many cells to undergo apoptosis (programmed cell death). These observations suggest that endogenous TGF-alpha is necessary for OCUH-16 cell growth.

Antibodies, Monoclonal↗

What is the risk factor for metachronous colorectal carcinoma?

PURPOSE: The purpose of this study was to determine the risk factors for developing metachronous colorectal carcinoma and to determine an adequate postoperative colonoscopic surveillance. METHODS: Two hundred eighty-four patients, examined by routine colonoscopy after resection for colorectal carcinoma, were reviewed. Clinical and pathologic factors were assessed by multiple logistic regression analysis. RESULTS: One hundred eighty-three patients with synchronous adenoma or carcinoma at the initial operation had a significantly higher incidence of both metachronous adenoma and carcinoma than the 101 patients without a synchronous lesion. Other clinical factors including age, gender, tumor stage, tumor site, and tumor grade were not significant for an increased incidence of metachronous carcinoma. The presence of synchronous lesions proved to be the only risk factor (relative risk, 3.293; P = 0.0155) for developing metachronous carcinoma. Metachronous carcinoma was detected in 30 patients (10.6 percent) and completely removed from all patients. Mucosal carcinoma was found in 25 patients (8.8 percent) and invasive carcinoma in 5 patients (1.8 percent). All five invasive carcinomas were detected in asymptomatic patients having synchronous lesion. Four patients required a second operation for metachronous carcinoma more than 13 months following the first. CONCLUSION: The risk factor for developing metachronous carcinoma is the presence of synchronous adenoma or carcinoma at the initial operation. To detect metachronous carcinoma at a curable stage, annual colonoscopic surveillance should be performed for high-risk patients.

Adenoma↗

Ischemic colitis arising in watershed areas of the colonic blood supply: a report of two cases.

There are several weak points in the colonic blood supply, known as watershed areas, which result from incomplete anastomoses of the marginal arteries. These watershed areas are more vulnerable to ischemic injury than other parts of the colon. We report herein the cases of two patients who developed ischemic colitis well localized in the cecum, and in the rectosigmoid region at Sudeck's point, respectively. This report and our review of the literature suggest that watershed areas, including the splenic flexure, or Griffith's point, Sudeck's point, and the ileocecal region, are high-risk regions for the development of ischemic colitis.

Colectomy↗

Beta 3-adrenergic-receptor polymorphism: a genetic marker for visceral fat obesity and the insulin resistance syndrome.

We investigated whether the polymorphism of the beta 3-adrenergic receptor (beta 3-AR) gene, which is associated with insulin resistance in non-diabetic subjects and an earlier onset of non-insulin-dependent diabetes mellitus in Pima Indians, was associated with visceral fat obesity and features of the insulin resistance syndrome in Japanese premenopausal obese women. There was no difference between 131 obese women and 256 control subjects (0.23 vs 0.17, p = 0.112) in the frequency of the Arg64 allele. The visceral fat area measured by computerised tomography scan was greater in homozygous Arg64Arg (172 +/- 17 cm2, n = 6) and heterozygous Trp64Arg (178 +/- 47 cm2, n = 48) women than in women homozygous for the Trp64Trp (121 +/- 46 cm2, n = 77) genotype (p < 0.01). This was also reflected by increased total body fat but not by increased body mass index. The association between the Trp64 allele and visceral fat mass by multiple regression analysis, was independent of age, body mass index and total fat mass (p < 0.004). Moreover, homozygous carriers of the Arg64 allele had higher systolic blood pressure, higher fasting and post-load glucose and insulin concentrations, higher cholesterol, and triglyceride and lower HDL-cholesterol concentrations than homozygous carriers of the Trp64 allele. Some of these differences were also observed between heterozygous Trp64Arg and homozygous Trp64Trp genotypes (glucose tolerance, insulin and cholesterol concentration). We conclude that in obese women the beta 3-AR polymorphism may be used as a genetic marker for visceral fat obesity and the insulin resistance syndrome.

Adipose Tissue↗

Adult onset globoid cell leukodystrophy (Krabbe disease): analysis of galactosylceramidase cDNA from four Japanese patients.

We examined galactosylceramidase (GALC) cDNA in four Japanese patients with adult onset globoid cell leukodystrophy (Krabbe disease; AO-GLD) by polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) analysis, subsequent sequence determination, and restriction enzyme digestion of PCR products, initial symptoms were the onset of slowly progressive spastic paraplegia from the middle of the second decade, and all patients had diminished GALC activity in their leukocytes. We identified three missense mutations (I66M, G270D, L618S) and one exon-6 skipping (535-573del). Two of the patients had only the I66M mutant mRNA, and one only the G27OD mutant mRNA. The fourth patient carried a compound heterozygous mutation of 535-573del and L618S. To determine the enzymatic activities produced by these mutations, we constructed mutated GALC cDNAs and expressed them in COS-1 cells. Three mutations, viz., G270D, L618S, and exon-6 skipping (535-573del), produced diminished GALC activity as expected. The I66M mutation in the wild-type GALC cDNA(I289) had normal activity, but when this mutation and the V289 polymorphism were introduced into the same allele, it had decreased activity. Thus, the combination of a unique mutation and polymorphism causes conformational change in the GALC enzyme, resulting in low enzymatic activity. AO-GLD mutations, including those found here, are located in the N-terminus (I66M, G270D, 535-573del) or C-terminus (L618S) of the GALC enzyme, whereas the reported mutations in the infantile form (IF-GLD) are in the central domain. This difference in mutation sites may affect the clinical features of GLD.

Adult↗

Do repolarization abnormalities in hypertrophic cardiomyopathy represent impaired fatty acid utilization? An observation with QRST isointegral maps.

To identify the clinical significance of the isointegral body surface map of the QRST interval (QRST map) and the occurrence of repolarization abnormalities in patients with hypertrophic cardiomyopathy (HCM), the QRST map and signal-averaged electrocardiogram were evaluated in 50 patients with HCM, in 33 of whom the results were compared with nuclear images both for radioiodine-labeled fatty acid metabolism and for radiothallium perfusion. The QRST departure map was used to determine two parameters of difference between patient and control recordings: the subnormal area (the number of lead points at which the departure index values were negative and lay more than 2 SDs from the mean of the normal control group) and the subnormal minimum (the absolute value of the minimum in the departure map). Late potentials were detected in 6 (12%) of the 50 patients; they were observed in 3 of the 5 patients with dilated-phase HCM but in only 3 (7%) of the other 45 patients. The subnormal area and minimum values were lower in nonobstructive HCM than in dilated-phase HCM. Of the 33 patients examined by myocardial imaging, 28 (33%) had a filling defect or decreased uptake, as shown on fatty acid metabolic images, and 10 of the 28 also showed abnormal myocardial perfusion images, while the 18 others showed normal perfusion images. These 28 patients showed significantly larger values of the subnormal area and minimum than patients with normal results in both image tests, regardless of whether or not myocardial perfusion imaging abnormalities were present. The localization of filling defects or of decreased uptake presented in fatty acid metabolic images corresponded to the position of the minimum on the QRST departure map. These results suggest that the QRST map is useful for detection of repolarization abnormalities in HCM and that these abnormalities are highly related to impaired fatty acid utilization of the myocardium.

Adolescent↗

Suppression of infectious virus spread and corneal opacification by the combined use of recombinant interferon beta and interleukin-10 following corneal infection with herpes simplex virus-1 in mice.

The effects of Interleukin-10 (IL-10) and recombinant murine interferon-beta (rMuIFN-beta) on experimental corneal herpes simplex virus 1 (HSV-1) inoculation in BALB/c mice were examined. The mice were inoculated with the HSV-1 strain KOS at their corneas after abrasion. IL-10 was then administered topically once a day for 10 days beginning 2 days post inoculation, while rMuIFN-beta was administered once a day for 10 days beginning 1 day post inoculation. The local viral growth in the inoculated eyes and trigeminal ganglia was reduced in the rMuIFN-beta-treated mice but not in the IL-10-treated mice. In the mice treated with both rMuIFN-beta and IL-10, the degree of both the local viral growth and corneal opacification decreased. The establishment of HSV-1 latency in the trigeminal ganglia was partially prevented by rMuIFN-beta treatment but not by IL-10 treatment. The combined use of the cytokines resulted in both the suppression of viral spread and the prevention of corneal inflammation induced by HSV-1 infection.

Animals↗