Chronic inflammatory demyelinating polyneuropathy with high titer of anti-sulfated glucuronyl paragloboside antibody.
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Antibodies↗
Biomedical subjects
S Miyamoto
Publications and source records attributed to S Miyamoto.
Characteristic difference in gastrointestinal excretion of clarithromycin and roxithromycin.
Excretion characteristics of two new macrolides; clarithromycin and roxithromycin, into the intestinal and the gastric lumens was studied by in situ single-pass perfusion and loop methods in rats. Roxithromycin maintained higher serum levels than clarithromycin after their intravenous administrations at a dose of 5 mg kg(-1) each. Radioactivities of clarithromycin and roxithromycin exsorbed into the intestinal lumen were 8.6 and 18.9% of dose in 2 h, respectively, whereas clarithromycin and roxithromycin excreted into the bile were 28.4 and 5.9%, respectively. These results suggest that roxithromycin is transported mainly by exsorption across the intestinal membrane, whereas clarithromycin mainly by excretion through the biliary tract. On the other hand, radioactivities of clarithromycin and roxithromycin exsorbed into the gastric lumen were much less then those into the intestinal lumen and were 0.72 and 1.34% of dose in 4 h, respectively. Thus, the exsorption into the gastric lumen seems to be a minor route for the elimination of both macrolides. Consequently, the transport into the intestinal lumen via the intestinal membrane and/or the bile tract may play a significant role in the overall elimination of both macrolides.
Animals↗
Outcomes for patients undergoing one or more total hip and knee arthroplasties.
Either total hip arthroplasty (THA), total knee arthroplasty (TKA) or both were performed in 105 patients from 1981 to 1994. These patients were experiencing severe joint destruction in the lower extremities due to rheumatoid arthritis (RA). These patients were followed for more than 2 years after their last operation. Eighty-six patients were alive and 19 patients had died at the time of follow-up. The 86 living patients were divided into four groups based on the number of replaced joints. Their pre- and postoperative conditions, including such factors as pain, mobility and disability for the quality of life (QOL), were compared. All of the four groups showed some reduction in pain and disability, and an improvement in ambulation after the operations. The 19 deceased patients were classified into two groups, one including those with multiple (three or four) arthroplasties and the other, those with only a small number (one or two). The mean age at death was lower (55.7+/-6.2 years) in patients with multiple arthroplasties than that (69.1+/-7.5 years) in patients with only a small number of arthroplasties. Secondary diseases from RA, such as amyloidosis, spinal injury and pulmonary fibrosis, were found to be the primary cause of death in patients with multiple arthroplasties. The most important finding in this study is that although RA patients with multiple arthroplasties in the lower extremities improved their QOL, they were still afflicted with secondary diseases derived from RA and experienced complications that could shorten their lifespan.
Adult↗
Intracranial gas on CT after cardiopulmonary resuscitation: 4 cases.
We report four patients in whom gas was seen in the head on CT shortly after cardiopulmonary resuscitation. The gas was in the posterior cranial fossa, presumably within veins, or in the cavernous sinus. The cause of the cardiac arrest was myocardial infarction in three patients and hanging in one. All had peripheral or central venous lines. The mechanism by which gas appeared in the intracranial veins is discussed.
Cardiopulmonary Resuscitation↗
Integrilin prevents prolonged bleeding times after cardiopulmonary bypass.
BACKGROUND: Cardiopulmonary bypass reduces platelet number and function, increases postoperative bleeding time, and is the major, unsolved cause of nonsurgical bleeding after open heart operations. Temporary inhibition of platelet function during cardiopulmonary bypass (platelet anesthesia) protects platelets and reduces postoperative bleeding time and bleeding. METHODS: Integrilin, a short-acting, reversible platelet glycoprotein IIb/IIIa inhibitor was studied in 28 baboons that had 60 minutes of normothermic cardiopulmonary bypass using peripheral cannulas. A control group, two groups that received different doses of Integrilin, and a group that received a combination of Integrilin and low-dose Iloprost were studied. Blood samples for platelet count, aggregation to adenosine diphosphate, beta-thromboglobulin, prothrombin fragment F1.2, thrombin-antithrombin complex, and fibrinopeptide A were obtained at seven time points. Template bleeding times were measured before and at five intervals after cardiopulmonary bypass. RESULTS: Both doses of Integrilin and the combination of Integrilin and Iloprost significantly protected platelet number, inhibited the response to adenosine diphosphate, and reduced postoperative bleeding times, but they did not reduce beta-thromboglobulin release except in the high-dose Integrilin group. Thrombin formation and activity were qualitatively, but not significantly, reduced in all treatment groups. Bleeding times were not significantly different from baseline at the time protamine was given in the combination group and 60 minutes after protamine administration in all treatment groups. CONCLUSIONS: Integrilin alone or in combination with Iloprost significantly reduces platelet activation during cardiopulmonary bypass and produces normal or near-normal bleeding times at the time protamine is given.
Animals↗
Enoxaparin suppresses thrombin formation and activity during cardiopulmonary bypass in baboons.
OBJECTIVE: This study tests the hypotheses that enoxaparin, a low molecular weight heparin and potent inhibitor of factor Xa, alone or in combination with standard heparin, inhibits thrombin formation and activity and modulates complement activation and neutrophil elastase release during cardiopulmonary bypass in baboons. METHODS: After preliminary studies to determine doses and possible species differences to anticoagulants and protamine, 27 anesthesized baboons had normothermic cardiopulmonary bypass with standard, unfractionated, porcine intestinal heparin, enoxaparin, or a combination of heparin and enoxaparin. Protamine in appropriate doses was used to reverse anticoagulation. Blood samples were obtained at 6 time points. Activated clotting times were monitored; template bleeding times were measured before and up to 24 hours after cardiopulmonary bypass. RESULTS: Hemodynamic measurements were not affected by the anticoagulant. Activated clotting times remained above 400 seconds throughout bypass, and no clots were observed. The anticoagulant did not alter platelet count, aggregation to adenosine diphosphate, release of beta-thromboglobulin, release of neutrophil elastase, or complement C3b/c and C4b/c. Enoxaparin alone, but not in combination, significantly reduced plasma levels of prothrombin fragment F1.2, fibrinopeptide A, and thrombin-antithrombin complexes but prolonged template bleeding times for more than 24 hours. CONCLUSION: Enoxaparin significantly reduces thrombin formation and activity during cardiopulmonary bypass but does not suppress complement activation and neutrophil elastase release and is not adequately reversed by protamine after bypass.
Animals↗
Alpha1-adrenoceptor subtypes and two receptor systems in vascular tissues.
The subtypes of alpha1-adrenoceptor are coexpressed in many tissues. We examined the relationship between coexpressed alpha1-adrenoceptor subtypes and their functions in blood vessels. Rat and rabbit aortas coexpressed three subtypes (alpha1A, alpha1B, alpha1D) and four subtypes (alpha1A, alpha1B, alpha1D, alpha1L), respectively. In rat aorta however, noradrenaline-induced contraction was mediated predominantly through the alpha1D subtype, and oxymetazoline produced alpha1B-mediated contraction. In rabbit aorta, concentration-response curves for noradrenaline were composed of two components (alpha1B and alpha1L-mediated), while oxymetazoline produced alpha1L-mediated contraction. Therefore, the inhibitory actions of some antagonists varied markedly among tissues and agonists. These results demonstrate diversity of the two receptor systems and suggest that the heterogeneity of physiological responses reflects the differences in functional subtypes among tissues and in their sensitivities to agonists and antagonists.
Adrenergic alpha-Agonists↗
Significance of increased plasma adrenomedullin concentration in patients with cirrhosis.
BACKGROUND/AIMS: Adrenomedullin recently discovered in human pheochromocytoma is a potent vasodilatory peptide mainly derived from vascular endothelial and smooth muscle cells. Hyperdynamic circulation, ultimately leading to ascites formation, has been attributed to peripheral vasodilatation in liver cirrhosis. However, little is known about the role of adrenomedullin in this condition. METHODS: Plasma adrenomedullin concentrations were measured by radioimmunoassay after extraction and purification in 28 cirrhotic patients without ascites, 12 cirrhotic patients with ascites and 10 healthy subjects. RESULTS: Plasma adrenomedullin concentrations in cirrhotic patients with ascites (12.7+/-4.5 fmol/ml) were significantly higher than those in cirrhotic patients without ascites (8.2+/-2.3 fmol/ml, p<0.005) and healthy subjects (5.8+/-0.8 fmol/ml, p<0.005). Interestingly, plasma adrenomedullin concentrations were highest in patients with refractory ascites (n=5, 15.8+/-3.0 fmol/ml) and were positively correlated with the Child-Pugh score (r=0.44, p<0.01). Moreover, plasma adrenomedullin concentrations were positively correlated with plasma renin activity (r=0.63, p<0.0001), plasma aldosterone (r=0.60, p<0.0001) and plasma norepinephrine concentrations (r=0.60, p<0.0001), and negatively correlated with creatinine clearance (r=-0.61, p<0.0005) and urinary sodium excretion (r=-0.44, p<0.02). Stepwise multiple regression analysis using certain independent variables, including Pugh's score, vasoactive substances, renal function and hemodynamic parameters, showed that the adjusted R square was highest when plasma renin activity and creatinine clearance (standard coefficient=0.53, -0.49, respectively) were considered (adjusted R square=0.61, p<0.0001). CONCLUSIONS: Plasma adrenomedullin concentrations increased with the progression of liver cirrhosis and were highest in cirrhotic patients with refractory ascites. In addition, elevated adrenomedullin was associated with activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, and with functional renal impairment in cirrhosis. Considering the potent vasodilatory action of adrenomedullin, increased adrenomedullin may participate in the hyperdynamic circulation, ultimately leading to ascites formation, in patients with liver cirrhosis.
Adrenomedullin↗
Structure-activity relationship of HIV-1 protease inhibitors containing AHPBA. Part III: Modification of P2 site.
The structure-activity relationship of HIV-1 protease (HIV-1 PR) inhibitors containing AHPBA (3-amino-2-hydroxy-4-phenylbutanoic acid) is discussed. In order to solve the problem of poor oral bioavailability, small-sized dipeptide HIV-1 protease inhibitors containing cyclic urethanes or benzamides at the P2 site were designed and prepared. The substitution patterns of the benzamides contributed significantly to their HIV-1 PR inhibitory activities, and it was shown that the choice of P2-residues was very important. Highly potent inhibitors possessing subnanomolar IC50 values and exhibiting good antiviral potency have been identified. In this class, inhibitor 18 was the most potent (IC90 (CEM/HIV-1 IIIB) 0.11 microM) and showed good oral bioavailability in dogs.
Animals↗
Synthesis and reactivities of 3-indocyanine-green-acyl-1,3-thiazolidine-2-thione (ICG-ATT) as a new near-infrared fluorescent-labeling reagent.
A new near-infrared fluorescent-labeling reagent (ICG-ATT) bearing the 3-acyl-1,3-thiazolidine-2-thione (ATT) moiety with the chemoselective acylation feature and the dye moiety of indocyanine green (ICG) has been developed. Synthesis and reactivities of the ICG-ATT are described.
Acylation↗
Diagnostic value of technetium-99m methoxyisobutyl isonitrile (99mTc-MIBI) scintigraphy in detecting thyroid cancer metastases: a critical evaluation.
Technetium-99m methoxyisobutyl isonitrile (99mTc-MIBI) scintigraphy has recently been used in clinical application for detecting thyroid cancer metastases, its role being considered supplementary to serum thyroglobulin (Tg) measurements and radioactive iodine (131I) whole-body scans (WBS). The present retrospective study was designed to elucidate the role of 99mTc-MIBI scans in localizing metastatic lesions by assessing sensitivity and specificity of the scan results obtained in a group of 68 thyroidectomized thyroid cancer patients. Presence or absence of thyroid cancer was judged with other diagnostic modes including serum Tg measurements, 131I WBS, bone scans, chest x-rays, computed tomography (CT), ultrasonography, histopathology, and evolution of disease during follow-up. All scans were read on lesion basis for detecting neck, lung, and bone metastases and also on region basis, namely head-neck, chest, and abdomen-pelvis-extremities (ab-p-ex) areas. The sensitivity of detection was 94.4% (17/18) for neck, 78.4% (40/51) for lung, and 92.8% (64/69) for skeletal lesions. Positive predictive value (PPV) and negative predictive value (NPV) were 96.3% (26/27) and 97.7% (43/44) for head-neck; 94.7% (71/75) and 50.0% (12/24) for chest; 100.0% (25/25) and 93.1% (54/58) for ab-p-ex regions, respectively. For all scan sites taken together, PPV and NPV were 96.1% (122/127) and 86.5% (109/126), respectively. In conclusion, the present study reveals that 99mTc-MIBI can be proposed as a first-line diagnostic agent for the follow-up protocol of thyroid cancer patients, although the ability to detect small lung metastases is somewhat limited.
Adult↗
Changes in bone mineral density after orchidectomy and hormone replacement therapy in individuals with androgen insensitivity syndrome.
Changes in bone mineral density (BMD) after orchidectomy and after hormone replacement therapy were reported in two patients with complete androgen insensitivity syndrome (AIS). Diagnosis of AIS was made by clinical features and confirmed by the presence of 46,XY karyotype and the presence of testis component in the removed gonads. BMD at the lumbar spine and at three sites of the femur was measured by dual energy X-ray absorptiometry (DXA). The Z scores of the lumbar spine BMD before orchidectomy were -0.8 and -3.1, confirming that patients with AIS have low BMD and that androgen plays an important role in bone mineralization in 46,XY individuals. Castration reduced BMD, but treatment with daily doses of 1.25 mg of conjugated oestrogen and 10 mg of medroxyprogesterone acetate increased BMD. These results indicate that both oestrogen and androgen play an important role in balancing BMD in men.
Adult↗
The effects of menopausal status and disease activity on biochemical markers of bone metabolism in female patients with rheumatoid arthritis.
The effects of menopause and disease activity on bone metabolism in rheumatoid arthritis (RA) were studied by using biochemical markers of bone metabolism. We measured osteocalcin, bone-specific alkaline phosphatase, urinary total pyridinoline and deoxypyridinoline, and urinary free deoxypyridinoline in 78 female patients with RA (39 pre-menopause, Pre-RA; 39 post-menopause, Post-RA) and 54 female normal controls (28 pre-menopause, Pre-NC; 26 post-menopause, Post-NC). In Pre-RA, although bone formation was equal to Pre-NC, bone resorption increased. In Post-RA, however, bone formation was lower while bone resorption was higher than in Post-NC. The high disease activity RA group showed higher bone turnover than the low disease activity RA group. We conclude that menopause affects the bone turnover in RA as well as in normal controls. In Pre-RA, osteopenia is caused by the increase in bone resorption. In Post-RA, osteopenia is caused by the increase in uncoupling between bone formation and bone resorption. Furthermore, the high disease activity of RA induces high bone turnover.
Adult↗
Peripheral primitive neuroectodermal tumor of the ovary confirmed by CD99 immunostaining, karyotypic analysis, and RT-PCR for EWS/FLI-1 chimeric mRNA.
We report a case of peripheral primitive neuroectodermal tumor (pPNET), which belongs to the PNET/Ewing's sarcoma family, arising in the left ovary of a 29-year-old woman. Microscopically, the tumor was composed of solid nests and sheets of monotonous, primitive, small round cells with a few rosettes, making it difficult to distinguish from small cell carcinoma of the ovary. Immunohistochemically, the tumor cells showed intense cell-membranous immunoreactivity for MIC2 protein (CD99). A short-term cell culture and karyotypic analysis revealed the tumor to possess a balanced t(11;22)(q24;q12) chromosomal translocation that is highly specific for tumors of the PNET/Ewing's sarcoma family. In addition, EWS/FLI-1 chimeric mRNA that originated from the characteristic chromosomal translocation was detected by reverse transcription-polymerase chain reaction. These results confirmed the diagnostic validity of the present tumor being a pPNET, thus raising the possibility that in the past, pPNETs which have arisen in the ovary may have been mistakenly diagnosed as small cell carcinomas of the ovary.
12E7 Antigen↗
Ventriculoatrial block during atrioventricular nodal reentrant tachycardia utilizing multiple retrograde pathways.
A rare case of narrow QRS tachycardia continuing despite the occurrence of VA block is reported. Right ventricular stimulation suggested dual AV nodal physiology. The tachycardia was induced by ventricular premature stimulation, which failed to depolarize the atrium. Two types of tachycardia that had different retrograde conduction sequences, HA intervals, and cycle lengths were induced. The occurrence of VA block did not terminate the tachycardia but transiently prolonged the tachycardia cycle length. These findings suggest the mechanism is AV nodal reentry utilizing multiple retrograde pathways with intranodal reentry bridging the VA block and maintaining the tachycardia.
Bundle of His↗
Detection of diaphragmatic defect as the cause of severe hepatic hydrothorax with magnetic resonance imaging.
Severe right-sided hepatic hydrothorax occurred in an 83-yr-old Japanese woman with a 7-yr history of cryptogenic liver cirrhosis. Transdiaphragmatic communication was indirectly suggested by rapid migration of dye (indocyanine green) from the peritoneal to the pleural space. Magnetic resonance imaging studies also demonstrated a diaphragmatic defect as a characteristic hypointense jet flow across the diaphragm on both T1- and T2-weighted sagittal scans. Although no firm treatment for hepatic hydrothorax has been established and direct demonstration of diaphragmatic defect with noninvasive imaging is extremely rare, testing for diaphragmatic integrity is meaningful to provide a radical or less invasive treatment. Magnetic resonance imaging, as well as color Doppler ultrasonography, may be useful for the detection of diaphragmatic defects as the cause of hepatic hydrothorax.
Aged↗
Novel IkappaB alpha proteolytic pathway in WEHI231 immature B cells.
The Rel/NF-kappaB family of transcription factors is sequestered in the cytoplasm of most mammalian cells by inhibitor proteins belonging to the IkappaB family. Degradation of IkappaB by a phosphorylation-dependent ubiquitin-proteasome (inducible) pathway is believed to allow nuclear transport of active Rel/NF-kappaB dimers. Rel/NF-kappaB (a p50-c-Rel dimer) is constitutively nuclear in murine B cells, such as WEHI231 cells. In these cells, p50, c-Rel, and IkappaB alpha are synthesized at high levels but only IkappaB alpha is rapidly degraded. We have examined the mechanism of IkappaB alpha degradation and its relation to constitutive p50-c-Rel activation. We demonstrate that all IkappaB alpha is found complexed with c-Rel protein in the cytoplasm. Additionally, rapid IkappaB alpha proteolysis is independent of but coexistent with the inducible pathway and can be inhibited by calcium chelators and some calpain inhibitors. Conditions that prevent degradation of IkappaB alpha also inhibit nuclear p50-c-Rel activity. Furthermore, the half-life of nuclear c-Rel is much shorter than that of the cytoplasmic form, underscoring the necessity for its continuous nuclear transport to maintain constitutive p50-c-Rel activity. We observed that IkappaB beta, another NF-kappaB inhibitor, is also complexed with c-Rel but slowly degraded by a proteasome-dependent process in WEHI231 cells. In addition, IkappaB beta is basally phosphorylated and cytoplasmic. We thus suggest that calcium-dependent IkappaB alpha proteolysis maintains nuclear transport of a p50-c-Rel heterodimer which in turn activates the synthesis of IkappaB alpha, p50, and c-Rel to sustain this dynamic process in WEHI231 B cells.
Animals↗
Comparison of bone regeneration in a rabbit skull defect by recombinant human BMP-2 incorporated in biodegradable hydrogel and in solution.
The objective of this study is to compare bone regeneration induced by recombinant human bone morphogenetic protein-2 (rhBMP-2) incorporated into a biodegradable gelatin hydrogel with that by rhBMP-2 in aqueous solution. After treating rabbit skull defects of 6 mm diameter with the two rhBMP-2 dosage forms, both of them increased the bone mineral density (BMD) at the skull defects with implantation time to a significantly higher extent than a rhBMP-2-free aqueous solution and a rhBMP-2-free empty gelatin hydrogel (p < 0.05). There was no quantifiable difference in BMD between the two dosage forms of rhBMP-2. Histological examination revealed that the integrity of newly generated bone increased with the rhBMP-2 dose, irrespective of the dosage form. The bone defect was filled with regenerated bone 21 days after treatment.
Absorptiometry, Photon↗