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Biomedical subjects

M Tsukamoto

Publications and source records attributed to M Tsukamoto.

At least 109 records · Page 6Linked to original sources

Detection of beta-2-glycoprotein-I-dependent antiphospholipid antibodies and anti-beta-2-glycoprotein-I antibody in patients with systemic lupus erythematosus and in patients with syphilis.

We investigated whether or not antiphospholipid antibodies (aPLs; antiphosphadidylserine antibody, aPS; antiphosphatididylinositol antibody, aPI; antiphosphatidic acid antibody, aPA, and antiphosphadidylethanolamine antibody, aPE) were beta 2-glycoprotein-I (GPI)-dependent antibodies like anticardiolipin antibody (aCL) in patients with systemic lupus erythematosus (SLE). None of the patients with syphilis or healthy controls was positive for any GPI-dependent aPL. By contrast, GPI-dependent aCL (40%), aPS (20%), aPI (18%), aPA (12%) and aPE (8%) were detected in patients with SLE. Among these, 4 patients were negative for aCL, but positive for aPS. Those who were positive for more than 2 types of aPL, along with lupus anticoagulant, had a high incidence of arteriovenous thrombosis, fetal loss, thrombocytopenia and biological false-positive reaction to syphilis. From these findings we conclude that GPI-dependent aPLs, other than aCL, are present in patients with SLE, and we should examine more than 2 types of aPL, such as a combination of aCL and aPS, to avoid overlooking aPL. Furthermore, we confirmed that GPI-independent aPL was not rare in SLE patients, but the clinical significance of this type of aPL in this clinical setting is unclear.

Adult↗

Anti-inflammatory and immunosuppressive effects of 1,6-anhydro-3,4-dideoxy-2-furfuryl-beta-D-threo-3-enopyranose (MT2221), a novel anhydro-enopyranose derivative, on experimental animal models.

The anti-inflammatory effects of 1,6-anhydro-3,4-dideoxy-2-furfuryl-beta-D-threo-3-enopyranose (MT2221) were investigated using animal models and compared with the effects of dexamethasone (DEX) and cyclosporin A (CYA). MT2221 inhibited carrageenan-induced acute inflammation and adjuvant arthritis in rats, as well as the delayed-type hypersensitive response and collagen-induced arthritis (CIA) in mice. However, it seemed that this compound was more effective against murine CIA than upon the other inflammation models. The MT2221 mode of action differed from those of conventional non-steroidal anti-inflammatory drugs (NSAIDs) and disease modifying anti-rheumatic drugs (DMARDs). All of these drugs are effective against acute inflammation or adjuvant arthritis models, but not against murine CIA. DEX and CYA did inhibit murine CIA, but in other animal models, their mode of action differed from that of MT2221. Moreover, allograft transplantation in mice showed that MT2221 slightly prolonged the allograft survival time. These results suggest that MT2221 has not only anti-inflammatory but also immunosuppressive effects based upon a novel mechanism of action that is different from NSAIDs, DMARDs, DEX and CYA.

Animals↗

[A case of pulmonary hypertensive crisis (PHC) treated with prostaglandin E1 and tolazolin after surgery of ventricular septal defect in an adult].

A 32-year-old woman was diagnosed with ventricular septal defect (VSD) with severe pulmonary hypertension (PH). Though Pp/Ps was 0.98, an operation was carried out because the index of pulmonary vascular disease (IPVD) was 1.73. Pp/Ps on the operation day was 0.51 and extubation was carried out on the next day. Five days after the operation, she suffered shock, convulsions and loss of consciousness, but these were relieved by endotracheal intubation. On the 7th day, because Pp/Ps was 0.97, we confirmed the diagnosis of PHC. PHC was treated by intravenous continuous infusion of a high dose of PGE1 (220 ng/kg/min) and tolazolin (Tz) (7-18 micrograms/kg/min) in combination with norepinephrine (0.07 microgram/kg/min) via a catheter in the descending aorta. Pp/Ps soon decreased and was 0.60 at 15 hours after administration of PGE1 and Tz. To prevent recurrent PHC, she was administered with PGE1 (20-60 ng/kg/min) intravenously for 3 weeks after improvement of PHC. As side effects of PGE1, she showed swelling and arthralgia of the hands and feet after 2 weeks. Those side effects improved after discontinuing of administration of PGE1.

Adult↗

beta 2-Glycoprotein I-dependent and-independent anticardiolipin antibody in patients with end-stage renal disease.

We investigated whether anticardiolipin antibody (aCL), which is common in patients with end-stage renal disease (ESRD), was dependent on beta 2-glycoprotein I (GPI), a cofactor of aCL. Lupus anticoagulant (LA) was identified in 13/39 hemodialysis (HD) patients. GPI-independent aCL was positive in 12/39 of this group, five of whom had both GPI-independent aCL and LA. Three of the 20 patients on symptomatic and supportive treatment other than HD had LA, but none of them were aCL positive. When GPI was added to the assay system to allow for GPI-dependent aCL measurement, the optical density (OD) readings of 10/12 HD patients decreased, thus proving that they were negative for aCL. In contrast, the OD readings of 6 control patients with systemic lupus erythematosus (SLE) increased markedly (3/6) or decreased slightly to moderately (3/6), however, within the limits of positive range, indicating GPI-dependent cCL positivity. These results suggested that LA and GPI-independent aCL were produced in ESRD patients, especially those on HD, possibly through mechanisms related to the hemodialysis membrane. However, the significance of GPI-independent aCL in this clinical setting, which may differ from the GPI-dependent aCL detected in SLE patients, as well as the possible participation of serum GPI in the production of aCL remain to be clarified.

Adult↗

Measurement of beta 2-glycoprotein I (apolipoprotein H)-independent anticardiolipin antibody in human immunodeficiency virus-1-positive and -negative hemophiliacs.

The authors studied whether or not anticardiolipin antibody (aCL), which is frequently detected in hemophiliacs with human immunodeficiency virus-1 (HIV-1) infection, is dependent on beta 2-glycoprotein I (GPI), a cofactor of cardiolipin (CL). GPI-independent aCL was positive in 27 of 36 hemophiliacs with HIV-1 antibody (75%) and in 23 of 29 patients without HIV-1 antibody (79%). However, only six HIV-1-positive and four HIV-1-negative patients were positive for GPI-dependent aCL. Thus the aCL in these hemophiliacs was GPI independent and therefore different from the aCL found in autoimmune diseases, such as systemic lupus erythematosus.

Antibodies, Anticardiolipin↗

Anticoagulant activity of an anti-beta 2-glycoprotein I antibody is dependent on the presence of beta 2-glycoprotein I.

We studied whether or not an anti-beta 2-glycoprotein I antibody (aGPI) had lupus anticoagulant-like activity, employing the diluted Russel viper venom time (dRVVT) and kaolin clotting time (KCT) as indices. aGPI prolonged the dRVVT and KCT of beta 2-glycoprotein I (GPI)-depleted normal plasma in the presence of extrinsic GPI. This prolongation of the dRVVT and KCT occurred immediately after the addition of aGPI and GPI, and was subsequently enhanced further in a time-dependent manner. The GPI/aGPI combination was judged to have lupus anticoagulant-like activity by the dRVVT-platelet neutralization test, but this was not confirmed by a lupus anticoagulant-specific test, i.e., the activated partial prothrombin time (APTT) using hexagonal phospholipid. From these findings, it can be concluded that aGPI has lupus anticoagulant-like activity in the presence of GPI, but may be a partially or considerably different antiphospholipid antibody from lupus anticoagulant. Further investigations may be needed to clarify this point.

Antibodies↗

Left ventricular pseudoaneurysm and intracardiac fistulas after replacement of mitral valve prosthesis.

Operation was performed on a 61-year-old woman with left ventricular pseudoaneurysm, left ventricular-right atrial fistula, and left ventricular-coronary sinus fistula after mitral valve replacement. The diagnostic and therapeutic approaches to these complications are described briefly, and the literature on intracardiac fistula after mitral valve replacement is reviewed.

Cardiomyopathies↗

Serum adenosine deaminase 2 and neopterin levels are increased in a majority of hemophiliacs irrespective of infection with human immunodeficiency virus type 1.

We investigated serum levels of adenosine deaminase 2 (ADA2) and neopterin (NP) in hemophiliacs with or without infection with human immunodeficiency virus type 1 (HIV-1). The mean (+/- SD) serum ADA2 level in hemophiliacs positive for HIV-1 (45.2 +/- 17.6 U/L) and negative for HIV-1 (34.9 +/- 15.8 U/L) was significantly higher than that in healthy controls (12.0 +/- 7.0 U/L) (P < .01). The mean serum NP level was also higher in HIV-1-positive hemophiliacs (10.2 +/- 6.1 nmol/L) and HIV-1-negative hemophiliacs (7.0 +/- 2.9 nmol/L) than in the healthy controls (4.3 +/- 1.3 nmol/L). Although the HIV-1-positive hemophiliacs had higher mean ADA2 and NP levels than did hemophiliacs in the HIV-1-negative group (P < .01), the levels of most of the patients in both groups were similar. ADA2 and NP levels in serial samples from asymptomatic carriers and patients with stable AIDS showed no marked changes over a period of up to 6 years. These findings indicate that ADA2 and NP are not specific markers of HIV-1 infection in hemophiliacs. Nonspecific immunologic activation due to the repeated infusion of antihemophilic factor concentrate could be one cause for the increased serum levels of ADA2 and NP in hemophiliacs.

Acquired Immunodeficiency Syndrome↗

Distinguishing beta 2-glycoprotein I dependent (systemic lupus erythematosus type) and independent (syphilis type) anticardiolipin antibody with Tween 20.

We investigated whether or not the use of Tween 20 could help to distinguish beta 2-glycoprotein I (GPI) independent anticardiolipin antibody (aCL) (syphilis-type aCL) from GPI-dependent aCL (SLE-type aCL) in a GPI-dependent/independent aCL ELISA. aCL was positive in all 16 SLE patients and all 15 syphilis patients, who were positive for aCL in the standard ELISA, in the GPI-independent ELISA with Tween 20. GPI-dependent aCL was detected in 12/16 SLE patients by the GPI-dependent ELISA with Tween 20. aCL was not detected in any of the syphilis patients by GPI-dependent ELISAs. On the basis of these results, we recommend that Tween 20 should be used in ELISAs to distinguish GPI-dependent aCL from GPI-independent aCL.

Adult↗

Tau protein kinase II is involved in the regulation of the normal phosphorylation state of tau protein.

To study the phosphorylation state of tau in vivo, we have prepared antisera by immunizing rabbits with synthetic phosphopeptides containing phosphoamino acids at specific sites that are potential targets for tau protein kinase II. Immunoblot experiments using these antisera demonstrated that tau in microtubule-associated proteins is phosphorylated at Ser144 and at Ser315. Almost all tau variants separated on two-dimensional gel electrophoresis were phosphorylated at Ser144 and nearly one-half of them at Ser315. Phosphorylation at Ser144 and at Thr147 of tau isolated from heat-stable brain extracts was shown to be developmentally regulated, with the highest level of phosphorylation found at postnatal week 1. In vitro phosphorylation of tau by tau protein kinase I, a kinase responsible for abnormal phosphorylation of tau found in paired helical filaments of patients with Alzheimer's disease, was enhanced by prior phosphorylation of tau by tau protein kinase II. Thus, we suggest that tau protein kinase II is indirectly involved, at least in part, in the regulation of the phosphorylation state of tau in neuronal cells.

Aging↗

Stimulation of Cl- and HCO3- secretion by intramural cholinergic neurons in guinea pig antrum in vitro.

Regulation of Cl- and HCO3- secretion by intramural cholinergic neurons was investigated in guinea pig antrum in vitro. Sheet preparations composed of the mucosa and the submucosa were mounted between Ussing chambers and bathed with buffer-free solution on the luminal surface and with HCO3(-)-CO2 solution on the serosal side. Short-circuit current (Isc), unidirectional fluxes of 36Cl and 22Na, and the luminal alkalinization rate (JOHSL) were determined. Electrical stimulation of the preparations elicited increases in both JOHSL and Isc, which were inhibited by tetrodotoxin (TTX) and atropine. Physostigmine also evoked TTX- and atropine-sensitive increases in JOHSL and Isc. Similar increases in JOHSL and Isc were observed when the muscarinic agonist bethanechol chloride (BCh) was added to the serosal side. The responses to BCh were not affected by TTX. The BCh-induced increase in JOHSL was largely abolished by removal of HCO3- or Na+ and addition of ouabain (serosal side) but was neither sensitive to Cl- removal nor associated with 22Na secretion. The increase in Isc induced by BCh was associated with the increase in 36Cl secretion and was inhibited by removal of Cl- or Na+ and by addition of bumetanide or ouabain (both, serosal side). These results suggest that the submucosal cholinergic neurons are involved via muscarinic receptors in the stimulation of epithelial HCO3- and Cl- secretion. For both HCO3- and Cl-, the cellular and membrane mechanisms of secretion induced by muscarinic stimulation, although not entirely clear, appear to be different from those occurring under baseline conditions.

Animals↗

Effect of distal gastrectomy on gut hormone release following vagal stimulation in dogs.

The effect of distal gastrectomy on gut hormone release was investigated by electrical stimulation of the posterior truncal vagus in dogs. Peripheral and portal plasma gastrin release was significantly inhibited, but peripheral and portal somatostatin release was unchanged. Peripheral and portal pancreatic polypeptide (PP) release was significantly inhibited. Our results suggest that the following factors might be some of the reasons why the secretion of PP was inhibited after distal gastrectomy: (1) transection of the posterior vagal branches close to the antrum and pylorus which might go to the pancreas; (2) changes in other hormones such as gastrin; (3) elimination of the PP secretagogue from the gastric antrum.

Animals↗

Surgical treatment of active infective endocarditis--early and late results of active native and prosthetic valve endocarditis.

The purpose of this study was to determine the clinical predictors of active infective endocarditis in 45 cases we treated between January 1971 and August 1991 (30 native valve endocarditis (NVE) and 15 prosthetic valve endocarditis (PVE). The indication of surgery in 45 patients was progressive congestive heart failure (CHF), septicemia and systemic embolization. The aortic valve was involved in 24 (53%) of 45 patients (13 of 30 NVE and 11 of 15 PVE) and there was significantly higher early mortality in aortic PVE (36%) than in aortic NVE (8%). The 9 patients with severe cardiac failure (NYHA Class V) before surgery were associated with a significantly higher incidence of early mortality (5/9 = 56%) than those in Class III (2/14 = 14%) and Class IV (3/18 = 17%). We concluded that aortic valve infection is more prevalent than mitral valve infection and is more often associated with staphylococcus infection, including abscess formation. Early surgical intervention should be performed despite the risk of cardiac failure and extensive infection.

Abscess↗

The treatment of intracapsular hip fractures with total hip arthroplasty in rheumatoid arthritis.

Total hip arthroplasty was performed on 41 patients with rheumatoid arthritis for 43 intracapsular hip fractures from 1971 to 1989. Followup, observation of clinical signs, and radiographs were conducted between one to ten years. Of the 41 patients, 25 had died by the end of the study. Total hip arthroplasty was found to be effective in relieving joint pain, and the walking ability of patients generally recovered to pre-injury status following the operation. Some patients experienced deterioration of the knee and ankle joints due to rheumatoid arthritis, and in such cases there was progressive loss of walking ability. Nevertheless, the function of the hip joint was well preserved, and most patients reported that pain had disappeared and the joint range of motion had returned to normal. In only one case was revision surgery necessary. There was little overall loosening of prostheses, and there were no problems concerning the durability of the artificial joint. The presence, therefore, of femoral neck fractures in patients with rheumatoid arthritis, who are to be encouraged to get out of bed and begin walking as soon as possible, is a strong indication for total hip arthroplasty.

Aged↗

Polymorphonuclear leucocyte function tests: a comparison of cytochrome C reduction and flow cytometric analysis.

Assay results were compared between the cytochrome C reduction test and flow cytometry using fluorescent beads or DCFH-DA (2', 7'-dichlorofluorescein diacetate) granules, in examining the phagocytosing and killing properties of polymorphonuclear leucocytes (PMN). When PMN samples from 20 healthy persons were assayed, no correlation was found between the cytochrome test and the phagocytosis (fluorescent beads) test or phagocytosing-killing (DCFH-DA) test by flow cytometry techniques. It is suggested that this might be caused by the fact that for technical reasons the two tests employed different stimulants and different substances to be phagocytosed. The simple flow cytometry procedure is now in widespread use as a PMN function test rather than the cytochrome C or nitroblue tetrazolium (NBT) dye reduction tests, and caution should be exercised in comparing and interpreting test results reported from separate laboratories. Because results using these two tests do not necessarily agree with each other, it seems preferable for PMN function testing to employ a combination of two or more approaches relying on different assay principles.

Adult↗