Bullous lichen planus.
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Biomedical subjects
Publications and source records attributed to S Handa.
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We investigated the clinical characteristics of acute myocardial infarction (AMI) not preceded by angina in 256 patients with first AMIs. Complications, including sustained ventricular tachycardia or ventricular fibrillation, pump failure and cardiac rupture, were more frequent in patients with AMI not preceded by angina (group 1, n = 92) than those preceded by angina (group 2, n = 164). The in-hospital mortality rate was higher in group 1 than in group 2. Poor preexisting collateral channels or lack of ischemic preconditioning may be responsible for the poorer outcome in group 1 patients.
The incidence of early reocclusion is reported to be higher in patients who receive fibrin-specific thrombolytic agents than nonspecific ones. The reason has yet to be clarified. In the present study, we focused on the difference in duration of fibrinolytic activity. The hemostatic parameters of 7 consecutive patients suffering from acute myocardial infarction treated with a fibrin-nonspecific thrombolytic agent (urokinase) were compared with 9 patients who received a fibrin-specific agent (tissue plasminogen activator, t-PA). The plasma concentrations of alpha 2-plasmin inhibitor (alpha 2-PI), plasmin alpha 2-PI complex (PLC), fibrin degradation products E fragment (FDP-E), and D-D dimer (D-dimer) were measured before, soon after, 1, 2, 3, 4, and 6 h and 2, 3, 4, and 7 days after thrombolytic therapy to estimate the hemostatic and fibrinolytic state. A significant decrease in alpha 2-PI (less than the lowest measurable level) with a simultaneous increase in FDP-E and D-dimer was induced soon after the administration of urokinase. FDP-E and D-dimer decreased, with a significant increase in alpha 2-PI, more than 6 h after thrombolytic therapy. In contrast, a less significant decrease in alpha 2-PI with a lesser amount and shorter duration of fibrinolysis were observed in patients who received t-PA. The amount of PIC soon after drug administration was not different between the two groups. Our data suggested that fibrinolytic activities induced by fibrin-nonspecific urokinase persisted longer than expected by its plasma half-life.The fibrinolytic activities might be terminated by the production of alpha 2-PI.(ABSTRACT TRUNCATED AT 250 WORDS)
Plasminogen activator inhibitor-1 (PAI-1), which is secreted from vascular endothelial cells, plays an important role in regulating fibrinolysis. We measured the plasma concentrations of tissue-type plasminogen activator (t-PA), PAI-1 and t-PA PAI complex before and serially after thrombolytic therapy for acute myocardial infarction to clarify the relationship between thrombolytic therapy and PAI-1. Plasma concentrations of t-PA, PAI-1 and t-PA PAI complex before thrombolytic therapy were 11.6 +/- 5.5, 27.0 +/- 13.0 and 7.3 +/- 5.4 ng/ml, respectively. t-PA and t-PA PAI complex increased to 25.0 +/- 5.3 and 14.3 +/- 6.5 ng/ml immediately after drug administration; however, the level of PAI-1 decreased slightly immediately after thrombolytic therapy. The PAI-1 level increased again several hours after therapy, especially in patients showing apparently successful reperfusion. All values returned to normal 4-7 days after thrombolytic therapy. Not only augmented antifibrinolytic activity suggested by increased PAI-1 but also augmented fibrinolytic activity suggested by increased t-PA was observed in patients with acute myocardial infarction. These abnormal findings persisted several days after coronary thrombolytic therapy.
OBJECTIVES: Protons produced during ischemia may increase intracellular Na+ (Na+i) through Na+/H+ exchange, and may lead to Ca2+ overload through Na+/Ca2+ exchange to cause myocardial stunning. This study investigated whether an increase in the H+ buffering capacity of the perfusate or a reduction of H+ production by a brief hypoxic preperfusion before ischemia would reduce myocardial stunning. We also investigated whether the protective effect of these maneuvers depends on the free [Ca2+] of the perfusate. METHODS: Isolated rat hearts were preperfused with oxygenated or hypoxic buffer (pH 7.4) containing 100 mM of either sucrose or HEPES for 10 min, followed by 15 min of total ischemia and 30 min of reperfusion. To investigate the dependence of the effects of HEPES or a brief hypoxic preperfusion, the free Ca2+ concentration in the buffer was changed from 1.25 mM to 2.5 mM in some hearts. RESULTS: Oxygenated preperfusion with buffer containing HEPES and 1.25 or 2.5 mM Ca2+ improved the metabolic and functional recovery with a decrease in the accumulation of Na+i during ischemia and in 45Ca2+ uptake during reperfusion. A brief hypoxic preperfusion with 1.25 mM Ca2+ provided a similar protective effect whereas no protective effect was observed when the [Ca2+] was raised to 2.5 mM. CONCLUSIONS: An increase in the H+ buffering capacity or a brief hypoxic preperfusion reduced myocardial stunning with improved metabolic recovery, and reduced Ca2+ uptake. However, the effects of these interventions were affected differently by the free [Ca2+] of the perfusate, which suggests that they work, at least in part, through some different mechanism(s).
The purpose of this study was to clarify the role of calcium flux in the pathogenesis of transient overshoot in regional myocardial contractile function after brief ischemia (post-ischemic hypercontraction). Six open-chest anesthetized dogs were examined. The left anterior descending coronary artery (LAD) was cannulated with a bypass system from the left carotid artery. Two minutes of total coronary occlusion of the LAD resulted in a post-ischemic hypercontraction 1 minute after reperfusion. Post-ischemic hypercontraction was abolished after reperfusion following 2 minutes of perfusion with anoxic Krebs-Henseleit solution containing 2.5 mM calcium. Post-ischemic hypercontraction occurred after calcium-free anoxic perfusion. The regional myocardial contractile function remained depressed 1 minute after reperfusion following anoxic perfusion with 5.0 mM calcium solution. Thus, post-ischemic hypercontraction was modified by the calcium concentration during anoxia. Alteration in transsarcolemmal calcium influx during reperfusion, which was modified by alterations in the calcium environment during anoxia, could be responsible for this phenomenon.
Coronary blood flow dynamics were investigated in 9 patients with isolated coronary artery disease of the left anterior descending artery (LAD) with good collateral flow (grade 2 or 3 of Rentrop's classification) from the right coronary artery (RCA) and 20 patients with normal coronary arteries as controls. The coronary flow velocity (Vs: systolic peak, Vd: diastolic peak, Vm: mean) was measured with a Doppler catheter and the diameter (D) by the edge detection method in the proximal portion of the RCA. Vs/Vd was calculated. The areas under the velocity curve during systole (integral of s) and diastole (integral of d) were measured to obtain the ratio (integral of s/integral of d). Peak to resting velocity ratio (PRVR) was obtained as an index of coronary flow reserve, using intracoronary injections of 6 ml contrast medium or 8-12 mg papaverine. These parameters before percutaneous transluminal coronary angioplasty (PTCA), after PTCA, and in control subjects were compared. The collaterals disappeared angiographically immediately after successful PTCA. D (before PTCA: 3.2 +/- 0.1 mm, after PTCA: 3.3 +/- 0.1 mm, controls: 3.2 +/- 0.1 mm) and Vs did not vary between before and after PTCA and in control subjects (NS). The values of Vd, Vm decreased and Vs/Vd and integral of s/integral of d increased after PTCA to the values in the controls. PRVR obtained with contrast medium and papaverine also increased.
The effects of coronary thrombolytic therapy with urokinase on the intrinsic hemostatic and fibrinolytic states were investigated by determining several markers for hemostatic and fibrinolytic activities in 6 patients with acute myocardial infarction who underwent coronary thrombolysis with urokinase. The markers for hemostasis and fibrinolysis were: markers for plasmin generation [alpha 2-plasmin inhibitor (alpha 2-PI), plasminogen, plasmin alpha 2-PI complex (PIC)]; markers for fibrinolysis [fibrin/fibrinogen degradation products-E fragment (FDP-E), FDP D-D dimer (D dimer), fibrinogen]; markers for hemostatic activity (prothrombin time (PT), antithrombin III (AT-III), protein C); markers for thrombin generation [thrombin antithrombin III complex (TAT)]; markers for intrinsic fibrinolytic activity [tissue plasminogen activator plasminogen activator inhibitor complex (TPA PAI complex)]. These markers were measured before, at 1 to 2 hours intervals during first 6 hours, daily during the next 3 days, and subsequently on the 7th and the 14th day after urokinase therapy. Fibrinolysis (determined by increased D dimer) occurred only when alpha 2-PI became unmeasurable with 96 x 10(4) or more units of urokinase administration, then persisted for more than 2 hours. TAT increased from 13.1 +/- 15.4 to 70.8 +/- 65.8 ng/ml soon after fibrinolysis occurred, indicating that thrombin generation occurred at the same time as fibrinolysis. The TPA PAI complex level before urokinase administration (26.4 +/- 6.4 ng/ml) was greater than the normal upper limit, indicating increased intrinsic fibrinolytic activity, then decreased after urokinase administration. These findings suggested that urokinase administration might affect the intrinsic fibrinolytic activity.(ABSTRACT TRUNCATED AT 250 WORDS)
S-1108 is a new oral esterified cephem antibiotic. Its active form, S-1006, has a broad antimicrobial spectrum against both Gram-positive and Gram-negative bacteria. Furthermore, S-1006 is extremely stable against beta-lactamases with some exceptions. In the present study, we conducted laboratory and clinical evaluations of S-1108 granules in pediatrics. The obtained results are summarized as follows. 1. A drug sensitivity test revealed that MIC80 of the drug against 456 clinical isolates of Staphylococcus aureus that had been kept in our laboratory was 6.25 micrograms/ml, similar to those of cefaclor (CCL) and methicillin (DMPPC). The most frequent MIC was 1.56 micrograms/ml against 20 strains of S. aureus isolated from patients who received this drug, and this value was similar to those for CCL, amoxicillin (AMPC) and DMPPC. As regards to Streptococcus pyogenes, MIC of S-1006 was < or = 0.025 microgram/ml against 449 clinical isolates in our culture collection and 7 strains obtained from patients who received this drug, and these MICs are similar to those of cefteram (CFTM). MICs of S-1006 against 5 strains of Streptococcus pneumoniae obtained from patients who received this drug were < or = 0.025 microgram/ml, 0.10 microgram/ml or 0.39 microgram/ml which are similar to those of CFTM. MICs of S-1006 against 4 strains of Haemophilus influenzae obtained from patients who received this drug were 0.05 or 0.10 microgram/ml which are similar to those of CFTM. 2. When S-1108 granule preparation was administered to 1 patient at 4.0 mg/kg, the peak plasma concentration of S-1006 was 1.25 microgram/ml. S-1108 granule preparation was also administered to 2 patients at 6.0 mg/kg, and the peak plasma concentrations were 2.43 micrograms/ml and 2.23 micrograms/ml. Plasma half-lives were 1.11 hours after 4.0 mg/kg and 1.28 hours in both patients given 6.0 micrograms/ml. AUCs were 4.06, 8.37 and 7.73 micrograms.hr/ml, respectively. A dose-response relationship was observed between the two doses. 3. Urinary concentration was the highest during the 4-6-hour period for a patient given 4.0 mg/kg, and during the 0-2-hour or 4-6-hour period for 2 patients given 6.0 mg/kg. The peak concentrations were 258.0, 602.0 and 500.0 micrograms/ml, respectively, and urinary recovery rates during the 0-8-hour period were 38.9, 38.3 and 23.1%, respectively. 4. Clinical effects were excellent or good in 88 of 93 patients, showing a very high efficacy rate of 94.6%.(ABSTRACT TRUNCATED AT 400 WORDS)
To examine sobriety factors which alcoholics understood being useful for recovery from alcoholism, a case-control study with self-completion questionnaires was conducted in 31 abstinent male alcoholics, aged 39-69 years (mean 53), who were taking part in Danshu-Kai (Japanese Abstinence meeting) for an average period of 5 years, and 31 age (+/- 5 years) matched male nonabstinent alcoholics, who were hospitalized because of alcoholism in a mental hospital for an average period of 7 months. The results indicated that abstinent alcoholics were significantly more married, employed, not hospitalized, having insight into disease as alcoholism, continuously abstinent over 2 years, and experienced in Danshu-Kai or Alcoholics Anonymous (A.A.) than nonabstinents, similarly understood that "Abstinence meeting" and "Family" significant factors for recovery from alcoholism, they realized that "Risky" was not effective for abstinence, whereas nonabstinents misunderstood that "Risky" was useful to their sobriety. It is suggested that "Stability of business", "Married life", and "Insight into disease" contribute to recovery from alcoholism; "Abstinence meeting", "Pertinent support by family" and "Recognition of Risky" are significant factors for sobriety.
In 1970, a 19 year-old man was diagnosed as having coarctation of the aorta (CoA). But the patient and his family rejected further examination for CoA and high blood pressure was treated after that time. When the patient was 37 years old, he was admitted to our hospital because of congestive heart failure. During the 2nd admission for determining the operability of CoA in December, 1988, non-sustained ventricular tachycardia was detected. Immediately, intravenous administration of lidocaine or/and mexiletine were started. However, cardiac arrest occurred. After his recovery, lethal ventricular arrhythmias were still observed frequently despite administration of class Ia or Ib antiarrhythmic drugs. Oral amiodarone administration (600 mg) with procainamide (1000 mg) was started on 1st of May, 1989. Axillo-femoral bypass graft was performed during the 2nd admission because curable operation was abandoned because of severely impaired cardiac function. Subsequently, the patient was admitted 5 times due to exacerbated congestive heart failure. However, lethal arrhythmias were able to be controlled by the combination of low dose amiodarone (100-200 mg) with procainamide until he died of congestive heart failure on 9th of May, 1992. We reported a rare adult case with CoA and severe heart failure. Lethal arrhythmias in this case were well controlled by the combined administration of low dose amiodarone with procainamide regardless of severely impaired cardiac function.
99mTc-tetrofosmin myocardial perfusion imagings under different protocols were performed at rest and stress on the same day. In the stress/rest protocol, the exercise study was carried out first, and then the rest one followed. Eight patients were involved in the stress/rest protocol. Seven patients were examined in the reverse, rest/stress protocol. In any protocols, the injection interval was 3 hours, and injection doses in the first and second studies were 370 MBq and 740 MBq, respectively. Myocardial counts were obtained by placing region of interest over the myocardial walls in short axial SPECT images. Based on myocardial counts from the first injection and the wash-out rate of tetrofosmin, we calculated, at the second imaging, counts caused from the first injection. Approximately 20-25% of counts in the second study were found to be caused from the residual radiotracer. The residual radiotracers affected the interpretation of imagings of two patients we examined: one with marked reversible ischemia examined in the stress/rest protocol and the other with mild ischemic change examined in the rest/stress one. Our results suggested that some modifications of studies, such as the increase in the injection intervals or the reduce of the first-to-second dose ratio, might be necessary to conduct the same day protocols.
The pathophysiology and the treatment of heart failure in patients with chronic cor pulmonale is described. The patients with chronic cor pulmonale were divided into two categories in terms of the cause of the disease, that is, due to chronic respiratory failure and due to chronic pulmonary vascular obstruction. The treatment for the patients in the first category is, mainly to control respiration and to continue chronic oxygen therapy, and in the second category is, to utilize vasodilator and anticoagulant therapy. The results of these treatments are rather poor, though in terms of improvement in the quality of life and the survival. In the patients with chronic respiratory disease, the prevention of chronic cor pulmonale and heart failure is essential.
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A novel sulfoglycosphingolipid based on the isoglobo-series core structure was isolated from rat kidney and purified by column chromatographies with DEAE-Sephadex and silica beads. The structure was characterized by solvolysis, compositional analysis, proton NMR spectroscopy, Fourier-transform infrared spectroscopy, methylation analysis and liquid secondary ion mass spectrometry (LSIMS). The characteristic fragment ions for a sulfate and a sulfated N-acetylhexosamine were observed in LSIMS spectra. The two-dimensional chemical-shift-correlated spectroscopy (COSY) and nuclear Overhauser enhancement spectroscopy experiments evidenced the presence of a 3-O-sulfated N-acetylgalactosamine and a Gal alpha 1-3Gal structure in the molecule. The major ceramide consisted of 4-hydroxysphinganine linked to a C24 nonhydroxy fatty acid, deduced from both compositional analysis and LSIMS. From the above results, the following structure was established for this glycolipid: HSO3-3GalNAc beta 1-3Gal alpha 1-3Gal beta 1-4Glc beta 1-1Cer, isoglobotetraosylceramide (iGb4Cer) IV3-sulfate. Rat kidney also contained globotetraosylceramide (Gb4Cer) IV3-sulfate which has a carbohydrate core identical to that from human kidney. The yields of iGb4Cer IV3-sulfate and Gb4Cer IV3-sulfate were 0.27 and 0.07 nmol/g wet tissue, respectively.
Gangliosides with NeuAc alpha 2-6Gal structure have been studied in human hepatocellular carcinoma. The gangliosides were purified to homogeneity by a DEAE-Sephadex A-25 column chromatography and by repeated silica beads column chromatography. Three gangliosides containing NeuAc alpha 2-6Gal structure were isolated and were structurally characterized by using monoclonal antibodies, proton nuclear magnetic resonance, fast atom bombardment mass spectrometry, methylation analysis by gas chromatography-mass spectrometry, and exoglycosidase treatments. The first compound was identified as NeuAc alpha 2-6Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1Cer. The structures of 2 other components were concluded to be as follows: [formula: see text] The first compound is a ganglioside that is characteristic of human meconium. The second compound has the same structure as a ganglioside recently found by us (Taki, T., Rokukawa, C., Kasama, T., Kon, K., Ando, S., Abe, T., and Handa, S., J. Biol. Chem., 267: 11811-11817, 1992) in meconium. The third compound is a novel type of ganglioside having blood group I-type structure as the core sequence. In addition to these gangliosides, 5 others were detected, and all except for GM3 were glycolipids with neolacto-series core structure. These results suggest that enzymes for the synthesis of neolacto type and NeuAc alpha 2-6Gal structure of glycolipids are activated in hepatoma.
The strain-dependent expression of murine serum amyloid P-component (SAP) has been known to be linked to the Sap locus. We have quantified the SAP mRNA in several inbred strains including DBA/2 and C57BL/6 mice which represent high and low producers of SAP at resting state, respectively, and found that the mRNA levels correlated well with the amount of SAP protein. Interestingly, the SAP mRNA level of F1 mouse between DBA/2 and C57BL/6 was low and similar to that of C57BL/6. Primer extension and ribonuclease (RNAase) protection analyses demonstrated that a single type of transcript was generated from the SAP gene and that the cap sites were identical regardless mouse strains tested under unstimulated and stimulated (by lipopolysaccharide (LPS) or interleukin-6 (IL-6)) conditions. To investigate possible structural difference of the SAP gene including 5' flanking region, we have cloned, sequenced and compared the SAP genes from DBA/2 and C57BL/6 mice. Sequence analyses revealed that the 5' flanking regulatory regions, as well as the coding regions, were well-conserved between the two strains. These results demonstrate that the strain-dependent SAP expression occurs at the transcriptional level but seems to be affected by neither different type of the transcripts nor structural difference of the 5' flanking and coding regions of the SAP gene. It was suggested that a possible transcription factor with suppressive activity, which is encoded by a gene linked to Sap, may be involved.
Three monosialogangliosides containing the NeuAc alpha 2-6Gal structure have been detected in human meconium by immunological analysis using a monoclonal antibody, MSG-15, and purified by repeated silica beads column chromatography. One was previously shown to be NeuAc alpha 2-6Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1Cer. The remaining two were characterized by proton NMR, fast atom bombardment mass spectrometry, methylation analysis by gas chromatography-mass spectrometry, and immunological studies, and their structures were concluded to be as follows. [formula: see text] The second ganglioside has the same structure that was isolated from bovine buttermilk (Takamizawa, K., Iwamori, M., Mutai, M., and Nagai, Y. (1986) J. Biol. Chem. 261, 5625-5630), and this is the first description of the occurrence of the ganglioside with the branched structure with two N-acetyllactosamines linked to lactosylceramide via beta 1-6 and beta 1-3 in human linked to lactosylceramide via beta 1-6 and beta 1-3 in human tissues. The third ganglioside is a novel ganglioside with blood group I-type and a NeuAc alpha 2-6Gal structure.