[Successful diagnosis and treatment of a case of cytomegalovirus infection in a previously healthy adult by antigenemia assay].
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Antigens, Viral↗
Biomedical subjects
S Nagata
Publications and source records attributed to S Nagata.
[A case of liver abscess caused by Streptococcus milleri].
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Amoxicillin↗
Possible involvement of ATP-dependent K-channel related mechanisms in the antihypertensive and cough suppressant effects of the novel ACE inhibitor (2S, 3aS, 7aS)-1-(N2-nicotinoyl-L-lysyl-gamma-D-glutamyl)octahydro-1H- indole-2-carboxylic acid.
The antihypertensive and cough suppressant mechanisms of DU-1777 ((2S,3aS,7aS)-1-(N2-nicotinoyl-L-lsyl-gamma-D-glutamyl )octahydro-1H-indole-2 -carboxylic acid, CAS 116662-73-8), a new long-acting angiotensin-1-converting enzyme (ACE) inhibitor, were investigated in vivo and in vitro. The antihypertensive effects of DU-1777 at 10 mg/kg p.o. and cromakalim at 0.3 mg/kg p.o. were partially (about 60%) or fully antagonized by glibenclamide at 10 mg/kg i.v. in 2-kidney, 1-clip renal hypertensive rats (2K-1C RHR). The antihypertensive effects of a Ca blocker (nifedipine) and other ACE inhibitors (captopril, alacepril, enalapril, lisinopril, imidapril and quanapril) were not antagonized by glibenclamide. In deoxycorticosterone acetate-salt hypertensive rats (DOCA-HR), the antihypertensive effects of DU-1777 at 3-30 mg/kg p.o. were fully antagonized by glibenclamide. However, in vitro, DU-1777 (10(-6)-10(-3) mol/l) did not affect aortic ring contractions induced by high K (30 mmol/l). In guinea pig, citric acid induced cough was increased by ACE inhibitors, captopril, alacepril, enalapril and lisinopril (10 and 30 mg/kg p.o.). DU-1777 had a tendency to decrease citric acid induced cough and the effect was antagonized by glibenclamide. These results suggest that while DU-1777 itself does not open ATP-dependent K channel, it indirectly produces these effects through unknown mechanisms in vivo. Moreover, these effects contributed to the antihypertensive effect in DOCA-HR and cough suppressant effect in guinea pigs.
Adenosine Triphosphate↗
Choice of replacement valve in the elderly.
BACKGROUND AND AIMS OF THE STUDY: Little comparative information exists on the outcome of the valve replacement with bioprostheses or mechanical valves in the elderly. This study was carried out to make such a comparison. METHODS: Follow up data were examined from 219 patients aged > or = 65 years who underwent aortic and/or mitral valve replacement using bioprosthetic (n = 67) or mechanical valve (n = 152) between April 1979 and December 1993. The mean follow up periods were 6.3 +/- 2.8 years after bioprosthesis and 4.9 +/- 2.1 years after mechanical valve implantation. RESULTS: Although the actuarial rate of structural deterioration was higher in patients with bioprosthetic valves than in those with mechanical valves (58% versus 100% freedom at 10 years after surgery, p < 0.01), no such prosthesis-related difference was seen in the subgroup of patients aged > or = 70 (100% versus 100% at nine years, p = N.S.). The actuarial rate of major bleeding was higher after mechanical valve implantation than after bioprosthetic valve placement (90% versus 100% freedom at 10 years, p < 0.05); this lower rate with bioprosthetic valves was maintained in patients aged > or = 70 (78% versus 100% at nine years, p < 0.05). There were no significant differences in the incidences of thromboembolism and bacterial endocarditis between the two valve types. CONCLUSIONS: Structural degeneration of bioprosthetic devices was a major problem in patients aged 65-70 years, but it was essentially negligible in those aged > or = 70 years. Anticoagulant-related bleeding was a major problem with mechanical valves in both age groups. Therefore, for patients older than 70 years, valve replacement with a bioprosthesis appears to be the method of choice.
Age Factors↗
[The relationship between workers' attitudes towards health, lifestyle and mental health].
In order to investigate the relationship between health practices, various psychosocial factors, and mental health, a survey was conducted by means of a self-rating questionnaire on 424 industrial workers. The questionnaire included items concerning Goldberg's 12 selected items from the Japanese version of the General Health Questionnaire, the Type A scale used in the Framingham study, Breslow's 7 health practices, and other original psychosocial, health practicing items. A total of 391 or 92.2% responded to the questionnaire. Among them, 354 (266 males and 88 females) complete responders to the GHQ were analysed for the present study. As a result, several factors such as decrease in age, perceived present illness, worsening of perceived health status, increase in anxiety concerning health, exacerbation of alcohol and smoking related behaviour, decrease in physical exercise, reduction of Breslow's 7 health practices, perceived stress and difficulty in dealing with stress, increase in stress content, negative and malfunctional coping strategies, and decrease in relaxation were, according to the GHQ scores, related to negative mental health. Furthermore, Type A scores were significantly correlated to GHQ scores, the number of stress factors, and Breslow's 7 health practices in males, but they were weak or had no correlation in females. It is considered that favorable health practices and attitudes towards health might help to maintain positive mental health, but further analysis is needed to determine their causal relationships because of the cross-sectional design of the present study.
Adaptation, Psychological↗
[Differential diagnosis of post-transfusion graft-versus-host disease (GVHD) by rapid immunopathologic examination of the skin].
The diagnosis of post-transfusion graft-versus-host disease (GVHD) in early period is critical for the prognosis of the patients. Exanthema and fever are the earliest symptom of the post-transfusion GVHD and usually precede the disturbance of the liver and bone marrow. Snap-frozen, cryostat-sectioned specimens from the lesional and perilesional skin were labeled by monoclonal antibodies against HLA-ABC, HLA- DR, ICAM-1, CD1a and CD8. The reaction was visualized by indirect immunofluorescence. Graft-versus-host reaction (GVHR) was immunopathologically characterized by extensive expression of HLA-DR and ICAM-1 in the epidermal keratinocytes, exocytosis of CD8 positive cytotoxic T-cell and the reduction or disappearance of CD1a expression by epidermal dendritic cells. The other GVHRs such as erythema exudativum multiforme (EEM), fixed drug eruption, toxic epidermal necrolysis (TEN) and lichen planus could not be separated. Our protocol of the immunopathologic examination could be done quickly (within 3 hours) and provides more detailed and useful information for the diagnosis of GVHD in early period compared with conventional histopathology.
Diagnosis, Differential↗
Clinical, morphologic, and biochemical characteristics of Chediak-Higashi syndrome in fifty-six Japanese black cattle.
OBJECTIVE: To characterize Chediak-Higashi syndrome (C-HS) in Japanese Black cattle. ANIMALS: 56 of 200 cattle with a bleeding disorder and giant granules in leukocytes. PROCEDURE: Clinical observation, CBC, hemostatic screening test, platelet aggregometry, electron microscopy, platelet constituent analysis, and ophthalmoscopic examination were done. RESULTS: Affected Japanese Black cattle had increased bleeding tendency and abnormal granules in their leukocytes. Susceptibility to infection was not increased. Cutaneous albinism was evident in 6 new-born calves, but not in most affected cattle. In all affected cattle, the tapetal fundus was pale and the nontapetal fundus was almost devoid of pigment. By electron microscopy, a remarkable decrease in the number of dense granules in platelets was observed. Functionally, collagen-induced platelet aggregation was markedly reduced. CONCLUSIONS: This bleeding disorder was diagnosed as C-HS. With regard to susceptibility to infection, albinism, and mortality, clinical manifestations of C-HS in Japanese Black cattle were moderate, compared with C-HS in human beings and Hereford cattle. CLINICAL RELEVANCE: Because an autosomal recessive mode of inheritance was documented and recessive homozygotes could be easily detected, C-HS in Japanese Black cattle can be controlled.
Adenosine Diphosphate↗
[Psychosocial evaluation on the correct recollection of periodic medical checkups of workers. 1. The ratio of correctly recalled results of medical checkups].
To investigate the usefulness of a periodic medical checkup at the workplace from the standpoint of remembering the results, a survey was performed by a self-rating questionnaire on 424 industrial workers in a certain manufacturing company. The questionnaire included several items, such as their recalled abnormal medical findings and follow-up toward them, Breslow's 7 health practices, Goldberg's 12 selected items from the Japanese version of the General Health Questionnaire, and other original health related items. The study was conducted a month after the workers received their results. A total of 391 (290 males and 101 females) or 92.2% responded to the questionnaire. Several factors, such as age, gender, the type of occupation, and perceived health status were significantly correlated to the recalled results of medical checkups, but, only age and the way of observing the results were in accordance with the actual results. Only forty-nine percent of the responders correctly remembered their results. Age and perceived health status were significantly correlated to the exact recollection of the results. In particular, those who had poor perceived health status tended to have a wrong understanding of their medical results. Furthermore, there were those with the highest averaged GHQ scores who responded as having some abnormal findings even though no abnormalities were discovered in the medical checkups. On the other hand, there were those with the lowest averaged GHQ scores who answered that they had no abnormal findings even though some abnormalities were revealed in the medical checkups. The frequency of correct follow-up of the results was lower than the exact recalling of the results. In addition, those who made a mistake in the follow-up were inclined to have an optimistic view. Therefore, comprehensive health care for precise recalling of the results of medical checkups should be required to improve abnormal findings or maintain a good health status.
Adult↗
[A resected case of intralobar pulmonary sequestration with increased serum tumor markers, CA19-9, CA125 and NCC-ST-439].
A 39-year old female was found to have intralobar pulmonary sequestration with a high serum level of the tumor markers, CA19-9, CA125 and NCC-ST-439. The lesion was located in the left S10 and an aberrant artery from the aorta was noted. After partial resection of the left lower lobe, serum levels of the tumor markers (CA19-9 2418U/ml, CA125 50.3U/ml, NCC-ST-439 13.0U/ml) gradually returned to normal. The half-life of serum CA19-9 was about 7 days. Immunohistochemical analysis revealed that CA19-9 was being produced in the bronchial epithelium of the sequestered lung. Increased serum levels of CA19-9 may be helpful in diagnosing pulmonary sequestration.
Adult↗
Cross-linking of Fas by antibodies to a peculiar domain of gp120 V3 loop can enhance T cell apoptosis in HIV-1-infected patients.
Previous studies have demonstrated that T cell-reactive antibodies in HIV-1 infection contribute to lymphocyte depletion by cytotoxicity that involves differential membrane targets, such as the 43.5-kD receptor on CEM cells. Here, we show that these antibodies bind Fas as result of a molecular mimicry of the gp120. Both flow cytometry and immunoblotting using the human Fas-transfected mouse WC8 lymphoma revealed positive binding of immunoglobulin G from several patients to a 43.8-kD membrane receptor that also reacts with the CH11 anti-Fas monoclonal antibody. Specificity to Fas was further confirmed to chimeric recombinant human Fas-Fc by ELISA, whereas overlapping peptide mapping of a Fas domain (VEINCTR-N) shared by gp120 V3 loop demonstrated a predominant affinity to the full-length 10-mer peptide. Four anti-Fas affinity preparations greatly increased the subdiploid DNA peak of CEM cells similar to agonist ligands of Fas. In addition, anti-Fas immunoglobulin G strongly inhibited the [3H]thymidine uptake of CEM cells in proliferative assays, inducing a suppression as high as provoked by both CH11 mAb and recombinant human Fas ligand. Since anti-Fas were reactive to gp120, it is conceivable that antibodies binding that domain within the V3 region are effective cross-linkers of Fas and increase apoptosis in peripheral T cells. These results suggest that autologous stimulation of the Fas pathway, rather than of lymphocytotoxic antibodies, may aggravate lymphopenia in a number of HIV-1+ subjects.
Acquired Immunodeficiency Syndrome↗
A trial to kill tumor cells through Fas (CD95)-mediated apoptosis in vivo.
We tried to induce tumor cell death in vivo through Fas (CD95)-mediated apoptosis. Murine hepatoma MH 134 (Fas-) was transfected with murine Fas antigen cDNA. Fas+ F6b but not Fas- N1d cells underwent apoptosis after treatment with anti-Fas antibody in vitro. The possibility of eradicating tumor cells in vivo with anti-Fas antibody was investigated using double-mutant gld/gld lpr/lpr mice which lack both Fas ligand (FasL) and Fas to avoid cytotoxic activity of the antibody to the liver and interference from endogenous FasL. A single administration of anti-Fas antibody efficiently suppressed the growth of F6b tumors but not that of N1d tumors in these mice. Thus, the therapy with Fas-FasL system may be a promising approach for cancer treatment, and this model is useful for study on in vivo apoptosis-mediated antitumor activity.
Animals↗
Novel neural adhesion molecules in the Contactin/F3 subgroup of the immunoglobulin superfamily: isolation and characterization of cDNAs from rat brain.
We cloned two kinds of cDNAs encoding novel Contactin/F3-subgroup adhesion molecules, which we termed NB-2 and NB-3. Nucleotide sequence analyses have shown that NB-2 and NB-3 are comprised of 1099 and 1028 amino acid residues, respectively. There was 51% similarity in the amino acid sequence of NB-2 and NB-3. NB-2 shared 46, 43, 55 and 55% identities with Contactin/F3, Tag-1, Big-1 and Big-2, respectively, at the amino acid sequence level. Likewise, the amino acid sequence of NB-3 exhibited 42, 44, 58 and 60% identities with Contactin/F3, Tag-1, Big-1 and Big-2, respectively. Expression of NB-2 mRNA was restricted to cerebrum, cerebellum and was hardly detectable, if any, in spinal cord. On the other hand, high expression of NB-3 mRNA was observed in spinal cord, as well as in cerebrum and cerebellum. In the other tissues, no expression of NB-2 and NB-3 mRNAs was detected.
Animals↗
Systemic injection of a tripeptide inhibits the intracellular activation of CPP32-like proteases in vivo and fully protects mice against Fas-mediated fulminant liver destruction and death.
Mice injected with anti-Fas antibody die within a few hours with total liver destruction due to massive apoptosis of hepatocytes. We show that this is preceded and accompanied by the sequential activation of cysteine proteases of the interleukin 1 beta-converting enzyme (ICE) and CPP32 types in the cytosol of the hepatocytes, and that proCPP32 cleavage and enzymatic activity can be prevented by intravenous injections of the tripeptide N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD.fmk), an inhibitor of ICE-like proteases. Four Z-VAD.fmk injections at 1-hour intervals abolished all signs of liver damage after anti-Fas antibody injection and resulted in 100% long-range recovery, without residual tissue damage, from a condition otherwise uniformly fatal within < 3 hours. This treatment was effective even when delayed until some liver DNA degradation was already detectable. Injections of the tetrapeptide Ac-YVAD.cmk, more specific for the ICE-like subfamily of cysteine proteases but less cell permeable, also gave protection, but at higher doses and when injections started before that of anti-Fas antibody. These observations afford a way of temporarily modulating a number of apoptotic processes in vivo and may have important therapeutic implications in some human diseases.
Amino Acid Chloromethyl Ketones↗
Apoptosis of mouse naive T cells induced by recombinant soluble Fas ligand and activation-induced resistance to Fas ligand.
We have investigated the susceptibility of mouse T cells at various maturation and activation stages to recombinant soluble mouse Fas ligand (termed WX1). CD4+CD8+ thymocytes were preferentially killed by WX1, although CD4+CD8- and CD4-CD8+ thymocytes were also killed at higher concentrations of WX1. The majority of CD4-CD8- thymocytes were resistant to the same doses of WX1. Naive peripheral T cells were also killed by WX1 at concentrations similar to those for single-positive thymocytes. Activation-induced cell death of previously activated T cells is known to be mediated by Fas and Fas ligand. However, the activation of naive splenic T cells by mAbs against CD3/TCR complex rather induced resistance against WX1. This resistance was induced in activated T cells but not in bystander T cells. These mechanisms seem to explain why activated T cells are not immediately killed and why bystander T cells are not activated in an Ag-nonspecific manner.
Animals↗
Mitral valve dysfunction resulting from thickening and stiffening of artificial mitral valve chordae.
BACKGROUND: There is little information about changes in mitral valve function caused by thickening and stiffening of artificial chordae during follow-up. Using serial echocardiographic examination, we evaluated thickening and stiffening of artificial chordae and the effect of those changes on mitral valve function. METHODS AND RESULTS: Between November 1986 and November 1993, 40 patients underwent mitral valve repair with artificial chordae using glutaraldehyde-tanned xenograft pericardium (GTXP) or polytetrafluoroethylene suture (PTFE). Seven GTXP patients and 20 PTFE patients underwent serial echocardiographic examination after surgery and were included in the final analysis. Thickening and stiffening of the artificial chonlae were classified according to echocardiographic changes after surgery: grade 1, no change; grade 2, thickening and/or stiffening without impairment of the motion of the mitral valve leaflet; and grade 3, thickening and stiffening that impaired motion of the mitral valve leaflet. The mean follow-ups in patients with GTXP and PTFE were 6.0 and 3.6 years, respectively. During follow-up, there were 2 GTXP patients with grade 2 thickening and stiffening and 4 patients with grade 3. There were 6 PTFE patients with grade 2 thickening and stiffening and 2 patients with grade 3. Grade 3 occurred earlier in GTXP than in PTFE patients (P < .05). Mitral valve area in GTXP patients decreased from 2.5 +/- 0.4 to 2.1 +/- 0.3 cm2 (P < .05); however, mitral valve area in PTFE patients showed no significant change during follow-up (2.1 +/- 0.4 to 2.0 +/- 0.4 cm2, P = NS). CONCLUSIONS: Although mitral valve repair with artificial chordae is useful, more attention should be paid to mitral valve function resulting from thickening and stiffening of artificial chordae.
Adult↗
Apoptosis: telling cells their time is up.
Ligand engagement by the receptor Fas leads to apoptosis. A clue to how this happens comes from the discovery that ligand binding leads to recruitment to Fas of a protease, homologous to interleukin-1 beta converting enzyme, likely to initiate a proteolytic cascade that drives apoptosis.
Amino Acid Sequence↗
Involvement of Fas ligand and Fas-mediated pathway in the cytotoxicity of human natural killer cells.
The cytotoxicity of NK cells has been thought to be mediated mainly by the perforin-dependent pathway. We investigated the involvement of Fas-mediated pathway in the killing activity of purified human CD3-, CD16+ NK cells. Fas ligand mRNA was expressed in freshly isolated NK cells. Apoptosis, which was identified by the fragmented chromatin in individual cells, was induced in the cells that expressed high levels of Fas via direct NK-to-target cell interaction or Ab-dependent cell-mediated cytotoxicity, even in Ca(2+)-free medium, in which perforin pores are known not to be formed. Apoptosis in both the presence and absence of external Ca2+ was inhibited by Fab of an anti-Fas mAb. Transfection of the Fas gene in target cells facilitated the induction of apoptosis, compared with the parental cell line. The function of the Fas-mediated pathway in the coexistence of the perforin-dependent pathway was examined in 10 cell lines expressing different levels of Fas by Ca2+ imaging and morphologic observation of single cells. With a certain boundary level, low or high levels of Fas expression in target cells were correlated to a great degree with either acute necrosis due to severe membrane damage after NK-target cell contact or apoptosis at a later period, respectively. We concluded that Fas ligand/Fas interaction is present and plays a significant role in the human NK cell-induced apoptosis.
Antibodies, Monoclonal↗
CPP32/Yama/apopain cleaves the catalytic component of DNA-dependent protein kinase in the holoenzyme.
DNA-dependent protein kinase (DNA-PK) is composed of a 460-kDa catalytic component (p460) and a DNA-binding component Ku protein. Immunoblot analysis after treatment of Jurkat cells with anti-Fas antibody demonstrated the cleavage of p460 concomitantly with an increase in CPP32/Yama/apopain activity. Recombinant CPP32/Yama/apopain specifically cleaved p460 in the DNA-PK preparation that had been purified from Raji cells into 230- and 160-kDa polypeptides, the latter of which was detected in anti-Fas-treated Jurkat cells. The regulatory component Ku protein was not significantly affected by CPP32/Yama/apopain. DNA-PK activity was decreased with the disappearance of p460 in the incubation of DNA-PK with CPP32/Yama/apopain. These results suggest that the catalytic component of DNA-PK is one of the target proteins for CPP32/Yama/apopain in Fas-mediated apoptosis.
Amino Acid Sequence↗