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Biomedical subjects

K Nishi

Publications and source records attributed to K Nishi.

At least 73 records · Page 4Linked to original sources

[A proposal of essentials for forensic pathological diagnosis of sudden infant death syndrome (SIDS)].

There are many sudden unexpected infant death cases which are easily diagnosed as sudden infant death syndrome (SIDS) both with or without autopsy in Japan. A SIDS diagnosis may provide a cover for accidental or criminal death. SIDS should not be a convenient diagnostic box that shelters the cases of unexpected infant death which lack the necessary antemortem information to make the correct diagnosis. The authors consider that SIDS should be diagnosed according to the direction of the international definition of SIDS, and propose the following essentials for a forensic pathological diagnosis. 1) A thorough autopsy should be performed based on precise autopsy protocol, including not only histological observation, but also, if necessary, toxicological, bacteriological, viral and/or biochemical examinations. 2) The forensic pathologist should be provided with pertinent information regarding antemortem health status, past clinical history, social circumstances, death scene investigation, etc. In order to collect more precise information, the authors recommend using a questionnaire such as the example in this report to record information from the deceased's guardians. 3) Suspicion of accidental death or infanticide should be completely ruled out. SIDS should be diagnosed only after these three essentials have been satisfied. When there is even a slight suspicion of accidental death or infanticide, or when the forensic pathologist can not obtain pertinent information about the deceased, the causes and classification of the death should be diagnosed as unspecified or undetermined. That is, the causes and classification of the death are undetermined as to whether it is a natural or unnatural death. Furthermore, several warning flags indicating a possible SIDS diagnosis were proposed: a case found dead in a supine position, the existence of a foreign body in the respiratory tract or mild infectious findings. The authors also emphasize the physician's responsibility to report a case found dead or dying of unnatural or clinically unexplained causes to the police. This is the crucial first step in getting an accurate diagnosis of SIDS.

Autopsy↗

[Pharmacokinetics of cisplatin and methotrexate in a patient suffering from advanced ureteral tumor accompanied by chronic renal failure, undergoing combined hemodialysis and systemic M-VAC chemotherapy].

The pharmacokinetics of cisplatin and methotrexate were determined in a patient suffering from advanced ureteral tumor accompanied by chronic renal failure undergoing 4 consecutive cycles of M-VAC chemotherapy and hemodialysis. No significant difference was observed in t1/2, AUC or CLtot of total platinum between the patient with the chronic renal failure and patients with normal renal function. The AUC and CLtot of free platinum in the patient with the chronic renal failure were higher and lower, respectively, than in the patients with normal renal function. The free cisplatin rebounded remarkably after the end of dialysis, which may be partly attributed to an increase in the AUC and decrease in CLtot. However, the dialysis index was about 75 and 85% in the 3rd and 4th cycles, respectively. The t1/2 and CLtot of methotrexate in the patient with the chronic renal failure tended to be longer and smaller than those in patients with normal renal function, respectively. Seventy-two hours after administration, the methotrexate level was 0.02 microM, which was not at the high-risk level of high-dose therapy. After four cycles of M-VAC therapy, the rest of the right ureteral tumor was extirpated and the clinical response was CR. In conclusion, it is considered that cisplatin and methotrexate can be given to a patient with chronic renal failure. However, the cisplatin and methotrexate serum levels must be monitored, even after very low doses.

Aged↗

[Significance of product documents (tenpubunsho) cited in judicial precedents in the field of anesthesiology].

The significance of the product documents (Tempubunsho) was mentioned in 21 out of 94 medical malpractice cases published in several laws reports 1963-97. The number of such cases has been increasing in recent years. Among the items described in the product documents, the precautions for use were most frequently mentioned (12 cases) followed by the instructions for administration and dosage (3 cases). In most cases, the judgment was against the medical institution involved due to the violation of legal obligations with respect to the contents of the product documents. Product documents will be taken much more seriously in future lawsuits. Attention should be focused on the contents of the product documents, especially when revised. When the administration of a drug deviates from the contents of the product document, medical evidence is required to support this deviation.

Anesthesiology↗

[Survey on postmortem examination to police surgeons and emergency physicians. Possibility of physicians' assist in mass-disaster].

We conducted a questionnaire survey of police surgeons and emergency physicians, inquiring about their experience of medicolegal investigation of death and their willingness to join a death investigation team in a major disaster. The questionnaire also asked about their knowledge about and interest in the forensic specialist system established by the Japanese Society of Legal Medicine. Police surgeons were generally willing to join an investigation team only if a disaster occurred in or close to their hometown, because they could not afford more than several days away from patient care. Although many of the emergency physicians were willing to join a death investigation team, they had difficulty in doing so without permission or orders from their employer or the authorities concerned. The survey found that the percentage of aged police surgeons was increasing among those surveyed. This fact, in combination with the current emphasis of postgraduate education on specialty training, threatens to cause a substantial lack of physicians available for medicolegal investigation of death. Therefore, it is urgently necessary to establish a system of training resident and emergency physicians in medicolegal investigation of death. In addition to providing postgraduate training in medicolegal investigation of death to prospective trainees who are emergency physicians at major hospitals in potential disaster-stricken areas, the medical school should incorporate forensic medicine in postgraduate training programs so that they can actively perform death investigation on disaster victims dying before or after arrival at their hospitals. Furthermore, the forensic community should make every effort to increase the number of autopsies in each department of forensic medicine and to expand the medical examiner system throughout Japan that is currently in practice only in the Metropolis of Tokyo and Yokohama, Nagoya, Osaka and Kobe Cities in order to incorporate forensic training in the postgraduate clinical training programs that will become compulsory in 2004.

Attitude of Health Personnel↗

Differential roles of Ca(2+)/calmodulin-dependent protein kinase II and mitogen-activated protein kinase activation in hippocampal long-term potentiation.

The roles of Ca(2+)/calmodulin-dependent protein kinase II (CaM kinase II) and mitogen-activated protein kinase (MAPK) in long-term potentiation (LTP) were investigated in the CA1 area of hippocampal slices, using electrophysiological and biochemical approaches. A brief high-frequency stimulation, but not low-frequency stimulation, delivered to Schaffer collateral/commissural afferents produced a stable LTP and activated both CaM kinase II and 42 kDa MAPK. Different from the activity of CaM kinase II, the increase in MAPK activity was transient. At a concentration of 50 microM, but not of 30 microM, PD098059, a potent inhibitor of MAPK kinase, markedly inhibited the induction of LTP. Although the two concentrations had similar inhibitory effects on MAPK activity, only 50 microM PD098059 suppressed the activation of CaM kinase II. Application of calmidazolium, an antagonist of calmodulin, blocked both CaM kinase II activation and the LTP induction without affecting the increase in 42 kDa MAPK activity. Application of neurotrophin brain-derived neurotrophic factor (BDNF) promoted the induction of LTP, with concomitant activation of CaM kinase II. Under the same conditions, BDNF failed to activate MAPK in hippocampal slices. These results indicate that, although the LTP induction is accompanied by increases in two kinase activities, only CaM kinase II activation is required for this event.

Animals↗

Identification of cytosolic aldehyde dehydrogenase 1 from non-small cell lung carcinomas as a flavopiridol-binding protein.

The synthetic flavone flavopiridol can be cytostatic or cytotoxic to mammalian cells, depending on the concentration of the drug and the duration of exposure. It has been shown to inhibit the cyclin-dependent kinase (CDK) family of cell cycle regulatory enzymes. However, the existence of additional potential targets for drug action remains a matter of interest to define. To identify cellular targets, flavopiridol was immobilized. CDKs, particularly CDK 4, bound weakly to immobilized flavopiridol when ATP was absent but not in its presence. Two proteins with molecular weights of 40 kDa and 120 kDa had high affinities to the immobilized flavopiridol independent of the presence of ATP. They were present in all cell lines analyzed: cervical (HeLa), prostate and non-small cell lung carcinoma (NSCLC) cell lines. A 60-kDa protein, which was present only in NSCLC cells and bound similarly well to immobilized flavopiridol, was identified as cytosolic aldehyde dehydrogenase class 1 (ALDH-1). The level of this protein correlated with the resistance of NSCLC cell lines to cytotoxicity caused by 500 nM flavopiridol but not higher flavopiridol concentrations. Despite binding to ALDH-1, there was no inhibition of dehydrogenase activity by flavopiridol concentrations as high as 20 microM and flavopiridol was not metabolized by ALDH-1. The results suggest that high cellular levels of ALDH-1 may reduce cytotoxicity of flavopiridol and contribute to relative resistance to the drug. This is the first report that flavopiridol binds to proteins other than CDKs.

Aldehyde Dehydrogenase↗

Tyrosine hydroxylase and aromatic L-amino acid decarboxylase do not coexist in neurons in the human anterior cingulate cortex.

Immunoreactivity for aromatic L-amino acid decarboxylase (AADC), the second step dopamine-synthesizing enzyme, was found immunohistochemically in neurons of the human anterior cingulate cortex (ACC). Most of these neurons were located in layers V and VI and subcortical white matter; a small number were occasionally found in layer III. Double immunohistochemistry for tyrosine hydroxylase (TH: the first step dopamine-synthesizing enzyme) and AADC revealed that no neuronal cell bodies in the ACC were doubly immunostained for TH and AADC, suggesting that these TH-only- or AADC-only-immunoreactive neurons were not dopaminergic. AADC neurons in the human ACC might transform L-DOPA to dopamine, droxidopa to noradrenaline, and/or 5-hydroxytryptophan to serotonin.

Adult↗

Improvement in CNS protective treatment in non-high-risk childhood acute lymphoblastic leukemia: report from the Japanese Children's Cancer and Leukemia Study Group.

BACKGROUND: Prevention of central nervous system (CNS) leukemia by early introduction of therapy to this sanctuary site is an essential component of modern treatment strategy for acute lymphoblastic leukemia (ALL). However, the optimal form of preventive CNS therapy remains debatable. PROCEDURE: To address this issue, we evaluated the efficacy of CNS preventive therapy for 572 children with ALL who achieved complete remission in the Children's Cancer and Leukemia Study Group (CCLSG) ALL874 (1987-1990) and ALL911 (1991-1993) studies. They received risk-directed therapy based on age and leukocyte count. In the ALL 874 study, the non-high-risk (low-risk [LR] + intermediate risk [IR]) patients were randomly assigned to the conventional cranial irradiation (CRT) regimen (L874A and I874A) and the high-dose methotrexate (HDMTX) regimen without CRT (L874B and I874B). The former patients received 18-Gy CRT plus 3 doses of intrathecal (i.t.) MTX and the latter patients received 3 courses of HDMTX at 2 g/m2 plus 13 doses of ITMTX (L874B) or 4 courses of HDMTX at 4.5 g/m2 plus 1 dose of ITMTX (I874B). RESULTS: The 7-year probabilities (+/- SE) of CNS relapse-free survival were 97.3% +/- 2.6% (L874A, n = 41) vs. 90.3% +/- 5.3% (L874B, n = 39) (P = 0.25) in the LR patients, and 100% (I874A, n = 55) vs. 78.5% +/- 6.5% (I874B, n = 54) (P = 0.002) in the IR patients. The corresponding disease-free survival (DFS) rates were 79.4% +/- 6.5% vs. 74.4% +/- 7.3% (P = 0.62) in the LR group and 63.3% +/- 6.8% vs. 58.3% +/- 7.2% (P = 0.66) in the IR group. Thus, the HDMTX regimen could not provide better protection of CNS relapse as compared with the CRT regimen, although their overall efficacy was not significantly different. In the ALL 911 study, intensive systemic chemotherapy with extended i,t, injections of MTX plus cytarabine achieved a high CNS relapse-free survival (98% +/- 1.9% at 7 years) and a favorable DFS (85.5% +/- 5% at 7 years) in the IR patients. The patients in the high-risk (HR) group in both ALL874 and ALL911 studies received the 18-Gy or 24-Gy CRT with intensive systemic chemotherapy. Their 7-year probabilities of CNS relapse-free survival ranged from 88% to 95%, among which the T-ALL patients had a risk of CNS leukemia, which was 3-4 times higher compared with B-precursor ALL patients. CONCLUSIONS: These results indicate that long-term intrathecal CNS prophylaxis as well as appropriate systemic therapy for the non-high-risk patients can provide protection against CNS relapse equivalent to that provided by cranial irradiation.

Adolescent↗

Erythrocytapheresis for chronically transfused children with sickle cell disease: an effective method for maintaining a low hemoglobin S level and reducing iron overload.

Cerebrovascular accident (CVA) is a major complication of sickle cell disease during childhood. Long-term transfusion reduces the hemoglobin S level and generally prevents recurrent stroke, but it also results in progressive iron overload that requires regular chelation therapy. Erythrocytapheresis offers an alternative approach aimed at reducing the iron accumulation. We reviewed the results of erythrocytapheresis in eight sickle cell patients (mean age of 12.1 years) at high risk for a first or recurrent stroke. They were maintained at the standard pre-transfusion hemoglobin S (Hb S) level of 30%. Over an average of 9 months of erythrocytapheresis, none of the patients developed complications related to the procedure or to the increased blood use. Ferritin levels decreased by a mean of 26.5% in all patients. When evaluating the ferritin level in five patients, who remained on chelation therapy with deferoxamine (DFO), the level dropped by a mean of 32%. The levels remained stable in the three patients who were not on DFO. The procedure is safe and effective in reducing iron overload and can obviate the need for chelation therapy, even when the target Hb S is maintained at the standard 30% range.

Adolescent↗

Pericardio-peritoneal drainage using a subcostal approach.

A 56-year-old man admitted to our hospital for cardiac tamponade due to dilated cardiomyopathy did not respond to treatment by usual medical means or surgery. Pericardio-peritoneal drainage was conducted using a subcostal approach. Seven months later, the patient remains well and free of signs of pericardial tamponade. This method has proved to be safe and effective in patients with persistent massive pericardial effusion.

Cardiac Tamponade↗

Expression of transforming growth factor (TGF)-alpha, TGF-beta(2) and interleukin 8 messenger RNA in postsurgical and cultured lens epithelial cells obtained from patients with senile cataracts.

BACKGROUND: Testing our hypothesis that residual lens epithelial cells (LEC) participate in the pseudophakic inflammation by producing cytokines, prostaglandins (PG) or both, we detected interleukin-1 (IL-1), IL-6, b-FGF and PGE(2) in the incubation medium of cultured LEC. This paper describes our subsequent work on the expression of TGF-alpha, TGF-beta(2), IL-4 and IL-8 mRNA in postsurgical and cultured LEC. METHODS: The anterior lens capsule with attached LEC was obtained by anterior capsulotomy during cataract surgery and cultured. Specimens in serum-free medium immediately after surgery or those in serum-added medium after 2 weeks of culture were used. Reverse transcriptase-polymerase chain reaction (PCR) and electrophoresis were used to detect mRNA coding for TGF-alpha, TGF-beta(2), IL-4 and IL-8 in human cataract LEC. RESULTS: Electrophoresis of the PCR products showed that appropriately sized amplification products were specific for TGF-alpha and TGF-beta(2) in the specimens immediately after surgery and after culturing, and IL-8 in the cultured LEC. IL-4 was not detected in either group of specimens. CONCLUSIONS: Human cataract LEC synthesize TGF-alpha and TGF-beta(2) mRNA in situ and after culturing, and the cultured LEC also synthesize IL-8 mRNA. These cytokines may be synthesized by LEC in vitro and play an important role in an autocrine or paracrine manner in the proliferative process of LEC after cataract surgery, which can cause inflammation and aftercataract.

Aged↗

Blockade of kit signaling induces transdifferentiation of interstitial cells of cajal to a smooth muscle phenotype.

BACKGROUND & AIMS: Interstitial cells of Cajal (ICC) serve as pacemaker cells and mediators of neurotransmission from the enteric nervous system to gastrointestinal muscles. ICC develop from mesenchymal cells that express c-Kit, and signaling via Kit receptors is necessary for normal development of ICC. We studied the fate of functionally developed ICC after blockade of Kit receptors to determine whether ICC undergo cell death or whether the phenotype of the cells is modified. The fate of undeveloped ICC was also investigated. METHODS: Neutralizing, anti-Kit monoclonal antibody (ACK2) was administered to mice for 8 days after birth. ICC in the small intestine were examined by immunohistochemistry and electron microscopy. Occurrence of apoptosis was also assayed. RESULTS: When Kit receptors were blocked, ICC nearly disappeared from the small intestine. Apoptosis was not detected in regions where ICC are normally distributed. Remaining Kit-immunopositive cells in the pacemaker region of the small intestine developed ultrastructural features similar to smooth muscle cells, including prominent filament bundles and expression of the muscle-specific intermediate filament protein, desmin, and smooth muscle myosin. ICC of the deep muscular plexus normally develop after birth in the mouse. Precursors of these cells remained in an undifferentiated state when Kit was blocked. CONCLUSIONS: These data, along with previous studies showing that ICC in the pacemaker region of the small intestine and longitudinal muscle cells develop from the same Kit-immunopositive precursor cells, suggest inherent plasticity between the ICC and smooth muscle cells that is regulated by Kit-dependent cell signaling.

Animals↗

Preventing posterior capsule opacification by creating a discontinuous sharp bend in the capsule.

PURPOSE: To clarify which factor--intraocular lens (IOL) design or material--contributes most to the inhibition of migrating lens epithelial cells (LECs). SETTING: Jinshikai Medical Foundation, Nishi Eye Hospital, Osaka, Japan. METHODS: After phacoemulsification, an acrylic IOL with sharp optic edges was implanted in 1 eye and a poly(methyl methacrylate) (PMMA) IOL with an optic design similar to that of the acrylic IOL in the contralateral eye of 4 rabbits. RESULTS: The Miyake view and histopathological findings 3 weeks after surgery revealed that the lens capsule wrapped tightly around the optic edges, conforming to a distinctly sharp rectangular bend there with both IOL types in all rabbits. The migrating-LECs were inhibited at the site, and a massive Soemmering's ring cataract was formed. CONCLUSIONS: The discontinuous sharp capsule bend created by the sharp optic edges in both IOL types appeared to induce contact inhibition of the migrating LECs. The preventive effect of an acrylic IOL on posterior capsule opacification may be design dependent.

Acrylic Resins↗

Changes in choice of method and lethality between last attempted and completed suicides: how did suicide attempters carry out their desire?

Some researchers have emphasized that, from the perspective of suicide prevention, research into the methods of suicide seemed to be particularly promising, as it has been shown repeatedly that restricting access to the prevailing method of suicide in a country will decrease suicide rates and that the lethality of the method used significantly correlated with the degree of intention to die. In this study, we examined changes in choice of method and the lethality score between the last attempted suicide (LAS) and completed suicide (CS) in 416 victims (male: 197, female: 219) to point out the tendency on their choice of method in LAS and CS. There was a significant difference in choice of suicide method between LAS and CS, and injury to themselves (33.7%) was the most common method of LAS, while hanging (37.5%) was the most common method of CS. The mean lethality score of CS method was significantly higher than that of LAS method in both sex groups, suggesting that at least one of the causes that drives suicide attempters to commit suicide finally may be the difference in the lethalities of LAS and CS. At the time of CS, suicidal victims tend to choose the same method as that of LAS again. These findings suggest that although suicide attempters tend to choose the same method, they will use a more lethal method if they change the suicide method. Interestingly, moreover, there was no sex difference in the percentage of the mean lethality score at CS.

Journal Article↗

Gene analysis and enzymatic properties of thermostable beta-glycosidase from Pyrococcus kodakaraensis KOD1.

A beta-glycosidase with broad substrate specificity was identified from a hyperthermophilic archaeon, Pyrococcus kodakaraensis KOD1. The gene encoding beta-glycosidase (Pk-gly) consists of 1449 nucleotides corresponding to a polypeptide of 483 amino acids. The protein showed similarity with other beta-glycosidases from family-1 glycosyl hydrolases, in particular, it showed high identity to beta-mannosidase from P. furiosus (55.7%), beta-glycosidase from Sulfolobus solfataricus (42.7%) and beta-glucosidase from P. furiosus (41.9%). The cloned gene was expressed in Escherichia coli and the recombinant protein was purified. The beta-glycosidase showed optimal activity at pH 6.5 and at an extremely high temperature of 100 degrees C, and had a half-life of 18 h at 90 degrees C. The beta-glycosidase hydrolyzed various pNp-beta-glycopyranosides, with kcat K(m) values in the order of pNp-beta-glucopyranoside = pNp-beta-mannopyranoside > pNp-beta-galactopyranoside > pNp-beta-xylopyranoside. pNp-beta-mannopyranoside was the substrate exhibiting the lowest K(m) value [0.254 mM] with a kcat K(m) ratio comparable to that of pNp-beta-glucopyranoside. This substrate specificity was distinct from previously reported beta-glycosidases. We observed that the region in PK-Gly corresponding to the fifth alpha-helix and beta-strand region of beta-glycosidase from S. solfataricus, which constitutes a large portion of the channel for substrate incorporation, displayed a chimeric structure, with the N-terminal region similar to beta-glycosidases and the C-terminal region similar to beta-mannosidases. An exo-type hydrolytic activity and transglycosylation activity were also observed towards cellooligomers.

Journal Article↗

Tissue-specific expression of Le(Y) antigen in high endothelial venules of human lymphoid tissues.

In this study, we demonstrated that the anti-Le(Y) antibody (BM-1) especially reacted with high endothelial venules (HEVs) in peripheral lymph nodes of blood group O individuals. The Le(Y) expression on HEVs showed a unique tissue-specific pattern, i.e., a large amount of the Le(Y) expression in peripheral lymph nodes and no or small amounts in mesenteric lymph node. Statistical analysis showed that there was the significant difference between the percentage of Le(Y)-positive HEVs in peripheral lymph nodes and mesenteric lymph nodes. No expression of Le(Y) was observed in vessels of Payer's patch, thymus, spleen and other non-lymphoid organs. In blood group A or B individuals, the reactivity between HEVs and anti-Le(Y) antibody increased after enzyme digestion with alpha-N-acetylgalactosaminidase or alpha-galactosidase. These findings show that the expression of difucosylated blood group ABH antigens are especially expressed on HEVs in peripheral lymph nodes. Furthermore, the tissue-specific pattern suggests that these antigens may be related to intercellular adhesion between lymphocytes and HEVs.

ABO Blood-Group System↗

A newly designed adapter for testing an ex vivo mitral valve apparatus.

Few instruments are currently available to test mitral valve function in an ex vivo state due to the technical difficulties involved. To investigate the native ex vivo mitral valve or prosthetic mitral valve with chordae, we developed a mitral valve adapter with an annulus suturing portion and 2 papillary muscle suturing sites that can be changed in angle, direction, and length of chordae. We used this adapter to test an ex vivo mitral apparatus in beagle dogs and evaluated the morphology and function of the mitral apparatus by endoscopy. Our newly designed mitral valve adapter proved extremely useful for examining the ex vivo mitral valve anatomy and function and for testing stentless mitral prostheses with annular-papillary muscle continuity.

Animals↗

Comparison of bronchoalveolar lavage cell findings in complete-resolution pneumonia and delayed-resolution pneumonia.

BACKGROUND: In some patients with bacterial pneumonia, the resolution of chest radiograph shadows are delayed. There have been many clinical and pathological studies on delayed-resolution pneumonia (DR). However, there are no reports concerning inflammatory cell findings of bronchoalveolar lavage (BAL) fluid in patients with DR. We compared the BAL fluid cell findings in patients with DR with those in patients with complete-resolution pneumonia (CR). METHODS: The subjects included six patients whose chest radiograph shadows were completely resolved within 2 weeks after an appropriate antibiotic administration (CR), and nine patients whose chest radiograph shadows were unresolved more than 2 weeks after the treatment (DR). BAL was done 2-3 weeks after the antibiotic treatment in both groups. We compared differential counts and lymphocyte subsets in BAL fluid among patients with CR, patients with DR, and asymptomatic subjects. RESULTS: There were no significant differences in BAL fluid cell findings between CR groups and asymptomatic groups. On the other hand, the percentages of lymphocytes, neutrophils and eosinophils in DR group were significantly increased compared with those in CR and normal groups. There was no significant difference in the CD4+/CD8+ ratio of BAL lymphocytes among the three groups. CONCLUSIONS: It is suggested that infiltration of inflammatory cells in the lung exists in DR, despite the disappearance of inflammatory reaction in the peripheral blood.

Adult↗