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Biomedical subjects

K Yoshida

Publications and source records attributed to K Yoshida.

At least 37 records · Page 2Linked to original sources

The measurement of low levels of factor VIII or factor IX in hemophilia A and hemophilia B plasma by clot waveform analysis and thrombin generation assay.

BACKGROUND: Precise assessment of clotting function is essential for monitoring of hemostatic treatment for hemophilias A and B. MATERIALS AND METHODS: Clot waveform analysis and thrombin generation assays were performed on factor (F) VIII- and FIX-deficient plasmas, which had been reconstituted with known amounts of recombinant FVIII (rFVIII) and affinity-purified FIX respectively. Clot waveforms were assessed qualitatively and quantitatively by measuring the parameters clotting time, maximum coagulation velocity (Min1), and maximum coagulation acceleration (Min2). The thrombin generation assay was also assessed qualitatively and measurements made of time to peak and peak height. RESULTS: Overall results obtained with both assays showed good correlation for both clotting factors confirming that the changes in clotting waveform reflected changes in thrombin generation. Both assays demonstrated a predictable dose response to the addition of FVIII or IX. However, clot waveform analysis was more sensitive than the thrombin generation assay, particularly in detecting very low levels (0-0.1 IU dL(-1)) of both factors. CONCLUSIONS: These data suggest that the application of clot waveform analysis to the routine management of the hemophiliacs could increase our understanding of the clinical significance of low levels of FVIII and FIX that cannot be measured by assays in current use. This may be particularly useful in the management of hemophiliacs with inhibitors or undergoing gene therapy.

Biometry↗

Association study between kynurenine 3-monooxygenase gene and schizophrenia in the Japanese population.

Several lines of evidence suggest that metabolic changes in the kynurenic acid (KYNA) pathway are related to the etiology of schizophrenia. The inhibitor of kynurenine 3-monooxygenase (KMO) is known to increase KYNA levels, and the KMO gene is located in the chromosome region associated with schizophrenia, 1q42-q44. Single-marker and haplotype analyses for 6-tag single nucleotide polymorphisms (SNPs) of KMO were performed (cases = 465, controls = 440). Significant association of rs2275163 with schizophrenia was observed by single-marker comparisons (P = 0.032) and haplotype analysis including this SNP (P = 0.0049). Significant association of rs2275163 and haplotype was not replicated using a second, independent set of samples (cases = 480, controls = 448) (P = 0.706 and P = 0.689, respectively). These results suggest that the KMO is unlikely to be related to the development of schizophrenia in Japanese.

Aged↗

Expression of glutamine synthetase and cell proliferation in human idiopathic epiretinal membrane.

BACKGROUND/AIM: The mechanisms of the cellular origin and cell proliferation in the idiopathic epiretinal membrane (ERM) are unsolved. The aim of this study was to examine the expression of cell cycle related molecules and glutamine synthetase (GS), which is expressed in Müller cells and their processes, in ERM tissues. METHODS: The ERMs were surgically removed using pars plana vitrectomy. Formalin fixed, paraffin embedded ERM tissues were analysed by immunohistochemistry with anti-cyclin D1, p27 (KIP1), proliferating cell nuclear antigen (PCNA), and GS antibodies. RESULTS: The histopathological findings showed that all the ERMs consisted of oval or spindle mononuclear cells with thin collagen-like tissues. Immunoreactivity for GS was detected in collagen-like tissues of ERM, presenting a continuous, isodense pattern. GS immunopositive cells in all cases expressed PCNA in their nuclei. Nuclear immunoreactivity for cyclin D1 was noted in the ERM constituent cells, whereas p27 (KIP1) positive nuclei were not detected. CONCLUSION: Cyclin D1 and PCNA were expressed in the idiopathic ERM, which was mainly derived from Müller cells and extensions of their processes.

Aged↗

Does informed consent exempt Japanese doctors from reporting therapeutic deaths?

The Japanese Medical Act section 21 states that doctors must report unnatural deaths to the police, even though the term "unnatural death" is not defined by law. However, many doctors are reluctant to report potential therapeutic deaths (PTDs). The Japanese Society of Legal Medicine has submitted guidelines for unnatural death, including PTD. These define a PTD as an unexpected death, the cause of which is unknown, but which is potentially related to medical practice. Such deaths are "reportable" to the coroner in the UK. In this study, we addressed the question of whether physicians would report each of eight hypothetical PTDs. Although the clinical societies (the Japan Society of Internal Medicine and the Japan Surgical Society) declare that doctors must report deaths due to gross negligence, 60% of the participants said that they would not report gross negligence involving an overdose in cases where they had obtained informed consent or had provided an explanation after the death occurred. This can be accounted for by the mistaken belief on the part of the participants that obtaining informed consent exempts Japanese physicians from the duty of reporting PTDs. The attitude of Japanese physicians is caused by the death investigation system, which is designed to discover whether a crime has been committed rather than focusing on the cause of death. Accordingly, the Japanese Government has decided to commission a pilot study from an independent organisation in which medical specialists will investigate PTDs in order to prevent deaths occurring as a result of gross negligence.

Accidental Falls↗

Medullary sponge kidney in a 10-year-old Shih Tzu dog.

Medullary sponge kidney was diagnosed in a 10-year-old male Shih Tzu dog with a long history of hyposthenuria, but with no other findings indicating renal failure or hormonal aberration. At the dog's death from heart failure, an autopsy was performed. On gross morphology, bilateral kidneys were normal size and had many cysts ranging from the corticomedullary junction to renal papillae. Histopathologic findings showed that almost all of the cysts were lined by monolayered or multilayered and columnar or cuboidal epithelium with chilium similar to epididymis. Immunohistochemically, all of these cells were strongly positive for AE1/AE3 and negative for vimentin. Many of these cells were positive for cytokeratin 7 (CK7), and only a few cells were positive for desmin. The results of staining are the same as those for epithelium of the collecting duct of normal canine kidney. This is the first report of this pathologic entity in the canine kidney.

Animals↗

[Diastolic heart failure in patients with aortic valve disease].

From March 2002 to August 2005, 53 patients with age between 30 and 86 underwent surgical treatment for aortic valve disease. Preoperative diastolic heart failure was observed in 15 cases (28.3%). Operative procedures consisted of aortic valve replacement (AVR) in 42 cases [AVR and mitral valve replacement (MVR) in 3], aortic valve plasty (AVP) in 2, and aortic root replacement in 4. Concomitant procedures included maze procedure in 2 cases, coronary artery bypass grafting (CABG) in 6, mitral valve surgery in 15, and tricuspid valve annuloplasty (TAP) in 8. There were 7 cases for patient-prosthesis mismatch (PPM) [13.2%]. There were 2 hospital deaths (both were low-output syndrome). Among the surgical survivors, there were 2 late cardiac-related complications (all cases were cardiac failure). There was no recurrence or re-operation. Although all cases had severe diastolic failure, their systolic function was almost normal. Our study suggested that in patients with aortic valve disease, not PPM but diastolic heart failure correlated strongly with postoperative event and survival.

Aged↗

[Mitral valve plasty through right thoracotomy with submammary skin incision].

A 30-year-old female with congestive heart failure was referred to our hospital and massive mitral regurgitation was detected on the echocardiography. She was a mother of 2 infants, and wished early recovery from surgery, cosmetic consideration to skin incision and future pregnancy. Her mitral valve was successfully repaired through right thoracotomy with submammary skin incision. Postoperative transthoracic Doppler echocardiography revealed no mitral regurgitation. The patient recovered uneventfully and was discharged on the 8th postoperative day. And she has been drug-free since then.

Adult↗

[Tracheobronchial injury].

We studied 6 cases of tracheobronchial injury due to the blunt chest truma in our department. All patients were male of 19 to 60 years of age. Injured sites were main bronchus in 2, tracheobronchial portion in 2, cervical trachea and main bronchus in 1, cervical trachea in 1. In a case of cervical tracheal injury and 2 cases of tracheobronchial injury, emergent operation was performed on the day of accident. Other cases with the main bronchial injury underwent conservative treatment at first, but subsequent bronchoplasty was necessary for them due to the bronchial stenosis. After the surgery for 2 cases of tracheobronchial injury, mechanical ventilation with double lumen tube was continued to reduce the airway pressure for the anastomotic sites. In conclusion, early surgical treatment is recommended for the airway injury and the respiratory management using double lumen tube after surgery may be helpful in preventing trouble at the anastomosis.

Adult↗

Infection of Rosellinia necatrix with purified viral particles of a member of Partitiviridae (RnPV1-W8).

Isolate W8 of the white root rot fungus, Rosellinia necatrix, harbors three dsRNA segments, L1-, L2- and M-dsRNAs, and showed an irregular colony margin, slow growth, and moderate virulence. The M-dsRNA was previously shown to be the genome of a partitivirus, RnPV1-W8. Here a transfection protocol was developed for RnPV1-W8. Protoplasts of two virus-free isolates of R. necatrix were inoculated with purified viral particles using a polyethylene glycol-mediated method. Virus infection was confirmed by electrophoresis and Northern analysis. RnPV1-W8 introduced into the new host isolates was transmissible via hyphal anastomosis. However, the infection had no effect on the morphology and virulence of infected isolates of R. necatrix. This is the first report on the transfection of a partitivirus for R. necatrix.

Ascomycota↗

Adenovirus-mediated interferon alpha gene transfer induces regional direct cytotoxicity and possible systemic immunity against pancreatic cancer.

We previously demonstrated a characteristically high sensitivity of pancreatic cancer cells to interferon alpha (IFN-alpha) gene transfer, which induced a more prominent growth suppression and cell death in pancreatic cancer cells than in other types of cancers and normal cells. The IFN-alpha protein can exhibit both direct cytotoxicity and indirect immunological antitumour activity. Here, we dissected and examined the two mechanisms, taking advantage of the fact that IFN-alpha did not show any cross-species activity in its in vivo effect. When a human IFN-alpha adenovirus was injected into subcutaneous xenografts of human pancreatic cancer cells in nude mice, tumour growth was significantly suppressed due to cell death in an adenoviral dose-dependent manner. The IFN-alpha protein concentration was markedly increased in the injected subcutaneous tumour, but leakage of the potent cytokine into the systemic blood circulation was minimal. When a mouse IFN-alpha adenovirus was injected into the same subcutaneous tumour system, all mice showed significant tumour inhibition, an effect that was dependent on the indirect antitumour activities of IFN-alpha, notably a stimulation of natural killer cells. Moreover, in this case, tumour regression was observed not only for the injected subcutaneous tumours but also for the untreated tumours at distant sites. This study suggested that a local IFN-alpha gene therapy is a promising therapeutic strategy for pancreatic cancer, due to its dual mechanisms of antitumour activities and lack of significant toxicity.

Adenoviridae↗

Evidence for complex multigenic inheritance of radiation AML susceptibility in mice revealed using a surrogate phenotypic assay.

The mapping of genes which affect individual cancer risk is an important but complex challenge. A surrogate assay of susceptibility to radiation-induced acute myeloid leukaemia (AML) in the mouse based on chromosomal radiosensitivity has been developed and validated. This assay was applied to the mapping of radiation-induced AML risk modifier loci by association with microsatellite markers. A region on chromosome (chr) 18 with strong association is identified and confirmed by backcross analysis. Additional loci on chrs 8 and 13 show significant association. A key candidate gene Rbbp8 on chr18 is identified. Rbbp8 is shown to be upregulated in response to X-irradiation in the AML sensitive CBA strain but not AML resistant C57BL/6 strain. This study demonstrates the strength of utilizing surrogate endpoints of cancer susceptibility in the mapping of mouse loci and identifies additional loci that may affect radiation cancer risk.

Acute Disease↗

Molecular characterization of a partitivirus from the plant pathogenic ascomycete Rosellinia necatrix.

The W8 isolate of the phytopathogenic fungus, Rosellinia necatrix that causes white root rot, contained three segments of double-stranded (ds) RNA, namely L1, L2 and M. Purified viral particles of about 25 nm in diameter contained an RNA segment with almost the same mobility as M-dsRNA, but the band was sensitive to S1 nuclease. Molecular analysis revealed that M-dsRNA consisted of two (RNA 1 and RNA 2) similarly sized species of 2299 and 2279 bp excluding an interrupted poly (A or U) tail of 16-51 bp. The predicted largest open reading frame in RNA 1 and RNA 2 was similar to those of RNA dependent RNA polymerase (RdRp) and coat protein (CP), respectively, encoded by the family Partitiviridae. The non-coding regions (NCR) of the two segments were similar (approximately 70% base identity) at the 5' end, but different at the 3' end. The NCR at the 3' end contained adenosine-uracil rich elements (AREs) in both segments. Northern analyses revealed RNA 1 and RNA 2 in mycelial and viral particle fractions. We coined the name Rosellinia necatrix partitivirus 1-W8 (RnPV1-W8) for M-dsRNA based on viral particle morphology and sequence information.

Amino Acid Sequence↗

Solid serous cystadenoma of the pancreas: MR imaging with pathologic correlation.

We report a case of solid type serous cystadenoma of the pancreas. Computed tomographic and magnetic resonance (MR) images showed a hypervascular solid tumor that was difficult to differentiate from endocrine tumor of the pancreas. However, the tumor showed marked hyperintensity similar to that of hepatic cyst on MR cholangiopancreatography, indicating not a solid but rather a cystic nature. MR cholangiopancreatography (heavily T2-weighted image) is quite useful for clearly differentiating solid from cystic tumors.

Cystadenoma, Serous↗

Chronic exercise accelerates the degeneration-regeneration cycle and downregulates insulin-like growth factor-1 in muscle of mdx mice.

The aim of this study was to examine the effects of chronic running exercise on degenerative-regenerative processes in the hindlimb muscles of dystrophin-deficient mdx mice. The number of large-sized degenerative-regenerative groups (DRGs) was markedly decreased, whereas that of small-sized DRGs was unchanged by exercise. Expression of insulin-like growth factor-1 (Igf1), as well as a myogenic factor MyoD (Myod1), was downregulated in mdx muscles by exercise. The downregulation of Igf1 may well correlate with the decrease in the population of early regenerating fibers, which existed predominantly in DRGs, because IGF-1 was mainly localized in these fibers. Our data indicate that chronic exercise may accelerate the active cycle of degeneration-regeneration in mdx skeletal muscles. This means that mdx skeletal muscles can temporarily cope with work-induced injury by enhancing muscle regeneration and repair, but we speculate that an early decline of IGF-1 will accelerate age-dependent muscle wasting and weakness in the later stage of life in mdx mice.

Adaptation, Physiological↗

Spontaneous lymphocyt ic thyroiditis in interferon regulatory factor-1 deficient non-obese diabetic mice.

Interferon regulatory factor-1 (IRF-1) is a transcription factor involved in interferon-mediated immune reaction, CD8+ T cell differentiation and development of T helper 1 immune reaction. We have recently demonstrated that IRF-1 is pivotal in iodine-induced lymphocytic thyroiditis (LT) in non-obese diabetic (NOD) mice. However, it remains unclear whether the mechanism involved in spontaneous LT is identical with iodine-induced LT in NOD mice. To determine the role of IRF-1 in spontaneous LT, we used IRF-1 deficient NOD mice as well as IRF-1 +/+ and +/- mice which were free from treatments for LT induction, and LT was evaluated at 24 weeks of age. IRF-1 +/+, +/- and -/- mice developed LT spontaneously, and there were no differences among the 3 IRF-1 genotypes in the incidence and severity of LT. Whereas both CD4+ and CD8+ T cells were present in the diseased thyroid of IRF-1 +/+ mice, CD8+ T cells were absent in the thyroid of IRF-1 -/- mice. MHC class II antigen expression was induced in the inflamed thyroid of IRF-1 -/- mice comparable to IRF-1 +/+ mice. There was a selective reduction in the number of CD8+ T cells in the spleen of IRF-1 -/- mice. IFNgamma production, but not IL-10, by concanavalin A-stimulated splenocytes was significantly reduced in IRF-1 deficient mice. These results suggest that IRF-1 plays only a minor role in spontaneous LT in NOD mice and, furthermore, the mechanism involved in spontaneous LT is different from that of iodine-induced LT in NOD mice.

Animals↗