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Biomedical subjects

M Sakaguchi

Publications and source records attributed to M Sakaguchi.

At least 19 recordsLinked to original sources

Glucocorticoid-induced diabetes mellitus: prevalence and risk factors in primary renal diseases.

BACKGROUND/AIMS: In patients with primary renal diseases the current knowledge of hyperglycemia associated with corticosteroid therapy is limited. We therefore examined the prevalence and risk factors of glucocorticoid-induced diabetes mellitus (DM) in primary renal diseases. METHODS: Patients were recruited with primary renal diseases who were started on corticosteroids between April 2002 and June 2005. In patients with DM, an impaired fasting glucose level and/or positive urinary glucose analyses before corticosteroids therapy were excluded. RESULTS: During corticosteroid therapy (initial dose: prednisolone 0.75 +/- 0.10 mg/kg/day), DM was newly diagnosed in 17 (40.5%) of 42 patients. All of the 17 patients were diagnosed as having DM by postprandial hyperglycemia at 2 h after lunch, although they had normal fasting blood glucose levels. Age (OR 1.40, 95% CI 1.06-1.84) and body mass index (OR 1.87, 95% CI 1.03-3.38) were determined as independent risk factors for glucocorticoid-induced DM. CONCLUSION: Over 40% of patients with primary renal disease developed DM during treatment with corticosteroids. A high age and high body mass index are the independent risk factors for glucocorticoid-induced DM. 24-hour urinary glucose analyses and postprandial plasma glucose are useful for detecting glucocorticoid-induced DM.

Adult↗

Fate of cystic ovarian follicles and the subsequent fertility of early postpartum dairy cows.

The fate of cystic ovarian follicles that developed spontaneously during the early postpartum period of 50 lactating dairy cows was traced by ultrasonography to characterise the follicular dynamics in relation to the fertility of the cows. The absence of postpartum ovulations caused by repeated waves of anovulatory large follicles was also characterised and evaluated. Fifteen of the 50 cows developed cystic follicles, and these follicles became follicular cysts in five of the 15 cows. Most of the cystic follicles emerged before the first postpartum ovulation of the cows. The transition from cystic follicles to follicular cysts delayed the cows' first ovulation, oestrus and insemination, but had less influence on their fertility after they had recovered spontaneously. In addition to the 15 cows that developed cystic follicles or follicular cysts, six of the cows had five to 13 waves of follicles before their first ovulation. These repeated waves of follicles caused a more severe delay in the early postpartum reproductive events but did not affect the cows' fertility.

Animals↗

The effects of a neutrophil elastase inhibitor on the postoperative respiratory failure of acute aortic dissection.

BACKGROUND: Postoperative respiratory failure is often encountered in patients suffering from acute aortic dissection (AAD) and is believed to be influenced by release of neutrophil elastase after cardiopulmonary bypass. Sivelestat is a specific neutrophil elastase inhibitor, and this study aims to evaluate the effects of sivelestat on postoperative respiratory failure due to AAD. METHODS AND RESULTS: Patients who were operated for AAD from January 2000 to April 2005 and who had less than 300 mmHg initial postoperative PaO (2)/FiO (2) were investigated retrospectively and divided into two groups. Group 1 (n = 9) received intravenous administration of sivelestat immediately after the operation, while Group II (n = 9) received no sivelestat. There were no significant differences between Group I and II with respect to patients' characteristics or background (age, body weight, operating time, cardiopulmonary bypass time, amount of bleeding, preoperative WBC number and initial PaO (2)/FiO (2)). Though patients in Group I showed a subtle improvement in certain parameters such as PaO (2)/FiO (2), A-aDO (2) and respiratory index (RI) over a 3-day observation period compared to those of Group II, there were no significant differences. Neither postoperative mechanical ventilation time nor ICU stay differed between Group I and II. However, Group I showed a significantly greater improvement in the ratio of RI to initial RI on the 3POD compared to that of Group II (61.6 +/- 44.2 % vs. 111.9 +/- 40.9 %, P = 0.02). CONCLUSION: Inhibiting the activity of the neutrophil elastase may attenuate the postoperative respiratory complications of patients with AAD.

Acute Disease↗

Identification of peptides containing T-cell epitopes of Japanese cedar (Cryptomeria japonica) pollen allergen (Cry j 1) in dogs.

Japanese cedar (Cryptomeria japonica, CJ) pollen has been known to cause atopic dermatitis in dogs in Japan. However, since the mechanism of the CJ antigen recognition is not well understood in dogs, it is difficult to develop effective immunotherapy for atopic dermatitis caused by sensitization to CJ pollen. In order to aim at development of a peptide immunotherapy, we tried to identify T-cell epitopes of a major allergen of CJ pollen, Cry j 1, in dogs sensitive to CJ pollen allergen. Peripheral blood mononuclear cells (PBMCs) obtained from 22 dogs experimentally sensitized to CJ pollen allergen and 5 atopic dogs sensitive to CJ pollen allergen were used for mapping of T-cell epitopes of Cry j 1 using 35 kinds of synthesized overlapping peptides of Cry j 1. Reactive peptides were identified based on the results of blastogenic responses of PBMCs against the peptides when the stimulation indices were beyond 2.0. Three reactive peptides were identical in a relatively high population of experimental dogs, which were Nos. 8 (p71-90) (41%), 10 (p91-110) (50%), and 11 (p101-120) (41%). It was considered that these synthesized peptides should contain T-cell epitopes of Cry j 1 in the dogs. However, there were no reactive peptides identical among the five atopic dogs spontaneously sensitive to CJ pollen. The population of dogs experimentally sensitized to CJ pollen antigen will be used in order to investigate effects of a peptide immunotherapy using the reactive peptides. The results in atopic dogs sensitive to CJ pollen antigen will also provide useful information on necessity to develop a tailor-made immunotherapy using reactive peptides in each dog.

Allergens↗

Production of virus-specific antiserum corresponding to sequences in the lactate dehydrogenase-elevating virus (LDV) ORF6 protein.

The elucidation of the antigenic structure of the envelope proteins of Arteriviridae which includes lactate dehydrogenase-elevating virus (LDV) will provide further understanding of a mechanism of strict host cell specificity. To analyze the linkage between LDV envelope proteins, M/VP-2 and VP-3, which may play an important role in viral infectivity, we generated specific antibody against M/VP-2 that has not been reported in previous studies. A synthetic polypeptide corresponding to the C-terminal region of LDV strain C (LDV-C) ORF6, which encodes M/VP-2, was chemically synthesized and coupled to keyhole limpet hemocyanin (KLH). The peptide was immunogenic in rabbits and induced antibody specific for viral protein. Western blotting and immunofluorescence analysis of virion M/VP-2 in infected macrophages showed that the antibody was able to react specifically with authentic virion protein. The immunoreactive antibody against LDV M/VP-2 described in this study will be useful for further studies of the specific roles of the envelope proteins in arterivirus assembly and infectivity.

Animals↗

Analysis of protein expression by mammalian cell lines stably expressing lactate dehydrogenase-elevating virus ORF 5 and ORF 6 proteins.

Lactate dehydrogenase-elevating virus (LDV) has a strict species-specificity. Because only a subset of mouse primary macrophages have been identified that can support LDV replication in vitro, the precise molecular mechanism of viral entry and replication remains unclear. To analyze the LDV envelope proteins, which probably mediate viral attachment to the host cell, we developed a mammalian system for stable co-expression of LDV open reading frame (ORF) 5- and ORF 6-encoded proteins (ORF 5 and ORF 6 proteins), which correspond to envelope VP-3 and M/VP-2, respectively, and compared these expressed proteins to the native ones. Western blotting analysis combined with N-glycanase digestion revealed that ORF 5 and ORF 6 proteins were similar in size to native VP-3 and M/VP-2, and that ORF 5 protein was N-glycosylated, like the native VP-3. Immunofluorescence microscopy revealed that both ORF 5 and ORF 6 proteins were distributed throughout the cytoplasm and were colocalized in most cells. Moreover, ORF 5 protein was localized both in the perinuclear region and the Golgi complex and transported to the cell surface. This mammalian expression system in which the exogenously expressed proteins closely resemble the native proteins will provide the experimental basis for further studies of the interactions between LDV envelope proteins and host cells.

Animals↗

Th1-dominant shift of T cell cytokine production, and subsequent reduction of serum immunoglobulin E response by administration in vivo of plasmid expressing Txk/Rlk, a member of Tec family tyrosine kinases, in a mouse model.

BACKGROUND: Th1 and Th2 cells, resulting from antigenic stimulation in the presence of IL-12 and IL-4, respectively, are implicated in the pathology of various diseases including allergic and autoimmune diseases. Txk/Rlk is a member of Tec family tyrosine kinases. We reported that Txk acts as a Th1-specific transcription factor in the T lymphocytes. OBJECTIVE: In this study we have asked whether administration of txk expression plasmid brings about a Th1/Th2 shift in vivo of the mice, and subsequent reduction of circulating IgE. METHODS: Mice were administered a txk expression plasmid with hemagglutinating virus of Japan (HVJ) envelope vector. Txk expressions in spleen cells were assessed by immunoblotting and immunocytochemical staining. Cytokine productions by the spleen cells and serum Ig concentrations were studied by ELISA. RESULTS: Administration of a txk expression plasmid with HVJ vector induced expression of Txk in the spleen cells. The spleen cells showed enhanced Th1-specific cytokine production; spleen cells from the txk administered mice produced more IFN-gamma as compared with those from control plasmid-administered mice in an antigen-specific manner. IL-2 and IL-4 secretions of the spleen cells were comparable between the two mouse groups. Txk administration did not reduce serum IgG concentration. It markedly reduced total IgE level and an IgG1/IgG2a ratio, reflection of Th1/Th2 balance, in sera. Furthermore, txk administration reduced ovalbumin (OVA)-specific IgE levels in sera of the OVA sensitized mice. CONCLUSION: Thus, Txk enhances IFN-gamma secretion and thus modulates Th1/Th2 cytokine balance, leading to reduction of serum IgE.

Animals↗

Increase of CC chemokine receptor 4-positive cells in the peripheral CD4 cells in dogs with atopic dermatitis or experimentally sensitized to Japanese cedar pollen.

BACKGROUND: Since dogs frequently develop allergic diseases, similar to those in humans, dogs represent a possible animal model for allergy in humans. In human atopic dermatitis (AD), CC chemokine receptor 4 (CCR4) has been shown to play an important role in the development of allergic inflammation of AD; however, the association between allergic reaction and CCR4 is not well understood in dogs. OBJECTIVE: To examine CCR4 expression in peripheral blood CD4+ cells in dogs that had AD and were experimentally sensitized with Japanese cedar pollen. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from 17 dogs with AD. The proportion of CCR4+ cells in peripheral blood CD4+ cells (CCR4/CD4) was evaluated by flow cytometry and compared with that in 10 healthy dogs. Similarly, in dogs that were experimentally sensitized to Japanese cedar pollen antigen, the proportion of CCR4/CD4 was examined pre- and post-sensitization. RESULTS: The proportion of CCR4/CD4 in dogs with AD was 40.3+/-3.3%, which was significantly higher than that in normal dogs (23.6+/-4.3%) (P<0.01). In the experimentally sensitized dogs, the proportion of CCR4/CD4 was 25.4+/-2.6% at pre-sensitization and it was significantly increased (29.8+/-2.9%) at post-sensitization (P<0.01). CONCLUSION: The proportion of CCR4+ cells in peripheral blood CD4+ cells was measured in dogs with allergic conditions. The present findings indicate that CCR4+ cells may be involved in the pathogenesis of allergy in dogs as in humans.

Allergens↗

Postpartum ovarian follicular dynamics and estrous activity in lactating dairy cows.

The objectives of this study were to characterize early postpartum follicular dynamics in dairy cows in relation to their estrual activity and subsequent reproductive performance using 50 (26 primiparous and 24 multiparous) lactating Holstein cows. Ovaries and uterine horns of postpartum lactating cows were examined by ultrasonography 3 times weekly and continued until first services occurred after a 45-d voluntary waiting period. No differences were detected in fertility between primiparous and multiparous cows. In 40 of 50 cows, first postpartum ovulation was observed within 4 follicular waves, and the follicular wave patterns and ovarian cycles in most cows returned to normal as in cattle having normal estrous cycles after the second postpartum ovulation. Cows with the longest intervals from calving to first ovulation produced the most milk and also had prolonged intervals to first estrous activity. Differences in follicular dynamics before first ovulation altered intervals to first estrus, first service, and uterine involution, but these differences did not affect pregnancy rate, number of services, and days open. First postpartum insemination after 3 follicular waves tended to have greater pregnancy rates than those after 2 follicular waves. First inseminations at first estrus could produce greater pregnancy rates than those at subsequent periods of estrus.

Animals↗

[The efficiency of nifekalant hydrochloride for the prevention of ventricular tachycardia during cardiac surgery].

Many cases have been successfully treated by us with experimented nifekalant hydrocholoride to prevent ventricular tachycardia (VT) during cardiac surgery. The 13 patients who underwent cardiac surgery at our hospital from 1999 to 2002 were retroactively given nifekalant hydrocholoride against VT. Lidocaine hydrochloride was not effective for VT, and it was difficult for 3 patients to be weaned for cardio-pulmonary bypass, while 6 patients needed aortic balloon pumping or percutaneous cardio-pulmonary support. Nifekalant hydrochloride suppressed VT induction in 9 patients (69.2%). Blood pressure and heart rate did not change, but QTc intervals were significantly increased with nifekalant hydrochloride (p < 0.005). Proarrhythmic events (Torsades de pointes) occurred in 2 patients, but none of the cases showed drug-induced worsening of cardiac function. Nifekalant hydrochloride is a class III antiarrhythmic drug that has been found to be effective against VT and ventricular fibrillation. While class I antiarrhythmic drugs are usually ineffective and induce severe heart failure, nifekalant hydrochloride can be effective.

Adult↗

[Mitral valve plasty and coronary artery bypass grafting under beating heart cardiopulmonary bypass for severe left ventricular dysfunction; report of a case].

A 54-year-old man with ischemic mitral regurgitation and severe heart failure due to broad myocardial infarction successfully underwent mitral valve plasty and coronary artery bypass grafting under beating heart. He had an old anterior myocardial infarction and was admitted to our hospital with acute inferior myocardial infarction. Two weeks later, the cathetelization revealed moderate mitral regurgitation and triple vessel coronary artery disease. We selected antegrade continuous blood perfusion for myocardial protection on operation. He recovered uneventfully and discharged on postoperative day 31. We could perform this procedure safety and satisfactorily, we could this procedure for heart valve operation with other complications.

Cardiac Surgical Procedures↗

Mechanical compression of the extracranial vertebral artery during neck rotation.

Using duplex ultrasonography (US), the authors showed compression of the extracranial vertebral artery (ECVA) during neck rotation in 5.0% of 1,108 patients. Age (per 10-year increase, OR 0.80, 95% CI 0.67 to 0.96), vessel diameters (per 0.5-mm diameter increase, OR 0.63, 95% CI 0.51 to 0.79), and symptoms upon neck rotation (OR 4.01, 95% CI 1.35 to 11.9) were associated with vessel compression. In one case, SPECT revealed decreased cerebral perfusion of the hindbrain during rotation. ECVA US is useful in identifying vessel compression, especially in patients with symptoms on neck rotation.

Aged↗

Analysis of sequential immunoglobulin E-binding epitope of Japanese cedar pollen allergen (Cry j 2) in humans, monkeys and mice.

BACKGROUND: Japanese cedar (Cryptomeria japonica; CJ) pollinosis has been reported to occur naturally in Japanese monkeys (Macaca fuscata) as well as in humans. Most human patients and monkeys with pollinosis have specific IgE for Cry j 2, a major allergen of CJ pollen. OBJECTIVE: The main purpose of this study was to identify IgE B cell epitopes of Cry j 2 using a synthetic peptide in humans, monkeys and mice. METHODS: We synthesized 38 overlapping peptides that span the entire length of Cry j 2. We examined the B cell epitopes of Cry j 2 that are recognized by IgE in the sera of human patients and monkeys with pollinosis and immunized mice using synthetic peptides of Cry j 2. We also examined the reaction of Cry j 2-specific mouse monoclonal IgG antibodies to the peptides. Furthermore, we conducted a histamine release assay with leucocytes from a pollinosis patient using human serum albumin (HSA) conjugated with the peptides as a B cell epitope. RESULTS: We found that 16 of the 20 pollinosis patients who had specific IgE to Cry j 2 also exhibited IgE reaction with some Cry j 2 peptides. Of these 16 patients, 10 exhibited IgE reaction with Cry j 2 peptide no. 13 (121GQCKWVNGREICNDRDRPTA140). Five of the seven monkeys with CJ pollinosis exhibited a reaction with peptide no. 13. Furthermore, IgE in mice immunized with Cry j 2 and two mouse monoclonal IgG antibodies reacted with peptide no. 13. Peptide no. 13-conjugated HSA showed the release of histamine from basophils. Furthermore, to determine the minimum epitope in peptide no. 13, we conducted an enzyme-linked immunosorbent assay inhibition test. The core of the epitope in humans, monkeys and mice was 124KWVNGREI131. CONCLUSION: We found that 124KWVNGREI131 is an important B cell epitope recognized by IgE in humans, monkeys and mice.

Animals↗

[Aortic valve replacement with a freestyle stentless valve using the modified subcoronary technique and hemiarch replacement for bicuspid aortic valve and ascending aortic aneurysma; report of a case].

An association between bicuspid aortic valve disease and ascending aortic aneurysma has long been recognized. Root replacement with a composite valve graft for such disease is a well-established technique. But it may involve serious technical difficulties, and may be a more time-consuming procedure than separate valve replacement and graft replacement. We performed an aortic valve replacement with Freestyle stentless valve using the modified subcoronary technique and hemiarch replacement for a 72-year-old man with severe aortic stenosis and ascending aortic aneurysma. Angiographic studies after surgery showed no residual aortic regurgitation (AR) and no deformity of aorta. This technique is an acceptable option for an aortic disease and ascending aneurysma in elderly patients.

Aged↗

Small intestinal metastasis from renal cell carcinoma exhibiting rare findings.

Small intestinal metastasis from renal cell carcinoma (RCC) has only rarely been described. We report two patients who developed small bowel metastases from RCC showing different clinicopathological characteristics. Both patients underwent hemilateral nephrectomy for RCC and developed lung metastases metachronously or simultaneously. One patient developed occlusive ileus caused by multiple polypoid tumours composed of sarcomatoid tissue in the jejunum shortly after nephrectomy. The other patient presented melaena due to bleeding from a Borrmann 2-like tumour in the jejunum six years after nephrectomy. Clinically, his disease was slow-growing. Sarcomatoid histology and Borrmann 2-like tumour in this report are rare findings in metastatic tumour of RCC in the small bowel.

Antineoplastic Agents↗

[Redo coronary artery bypass operation under beating heart via the left thoracotomy reusing patent grafts].

We report three cases of successful redo coronary artery bypass grafting (CABG) under beating heart via left thoracotomy with recycling of patent grafts previously implanted. Case 1 and 2: Anginal attack relapsed due to occlusion of the proximal portions of saphenous vein grafts (SVG) that had been sequentially anastomosed to the left coronary artery branches. In each case, the distal portion of the SVG was patent and functioned as coronary-coronary bypass. The left internal thoracic artery graft (ITAG) anastomosed to the left anterior descending coronary artery (LAD) was patent. Each patient underwent off-pump CABG through a left posterolateral thoracotomy. CABG was performed with the radial artery to the circumflex coronary artery (case 1) or the circumflex coronary artery and previous SVG (case 2). The proximal ends of radial artery grafts were anastomosed to the descending aorta. Case 3: Simultaneous reoperative CABG and the operation for the pseudoaneurysm that developed after the abdominal aortic graft replacement were performed. Bypass grafting between ITAG and LAD was performed with SVG via a left anterolateral thoracotomy because of severe anastomotic stricture of ITAG-LAD. The postoperative courses was uneventful for all patients.

Aged↗