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Biomedical subjects

A Kanda

Publications and source records attributed to A Kanda.

At least 55 records · Page 3Linked to original sources

Cutaneous metastasis of an osteosarcoma. A case report.

Sarcomas seldom metastasize to the skin. This report describes a rare instance of this phenomenon. A 24-year-old patient with a history of osteosarcoma (osteoblastic type) of the right humerus was seen with a cutaneous nodule on the left temple. Histologic examination of the skin showed the lesion to be a metastatic osteosarcoma. On histologic examination, a proliferation of bizarre mononucleated or multinucleated osteoblastic cells was noted in the dermis and subcutis. Although osteoid formation and calcification were not recognized, as they had been in contrast to the primary lesion, basic structures and components of the skin lesion were identical to those of the primary tumor tissue. Cutaneous metastasis from on osteosarcoma of bone is an extraordinarily rare event and, as far as we can determine, has only been reported three times.

Adult↗

Multiple milia localized to the vulva.

Milia are most commonly observed on the cheeks and eyelids. We studied a case of multiple milia localized to the vulva in a 64-year-old female. A review of English and Japanese literature for the last 20 years failed to uncover any reports of milia limited to this area. We describe this case in detail and provide a short review of the literature on cysts of the genitalia.

Epidermal Cyst↗

Construction of a promoter probe vector autonomously maintained in Aspergillus and characterization of promoter regions derived from A. niger and A. oryzae genomes.

We used a plasmid carrying a sequence for autonomous maintenance in Aspergillus (AMA1) and the E. coli uidA gene as a reporter gene to search the A. oryzae and A. niger genomes for DNA fragments having strong promoter activity. Beta-glucuronidase (GUS)-producing A. oryzae transformants containing the No. 8AN derived from A. niger, or the No. 9AO derived from A. oryzae, were constitutive for the expression of the uidA gene when cultivated in the presence of a variety of carbon and nitrogen sources. When the GUS-producing transformants were grown in liquid culture, the No. 8AN showed an increase of approximately 3-fold in GUS activity compared to the amyB (alpha-amylase encoding gene) promoter. There was also a corresponding increase in the amount of GUS gene-specific mRNA. When these transformants were grown as rice-koji, the No. 8AN showed an increase of approximately 6-fold compared to the amyB promoter, and the amount of GUS protein produced also increased. These strong promoter regions might be applicable to the production of other heterologous proteins in Aspergillus species.

Aspergillus niger↗

Anticardiolipin antibodies in Crohn's disease associated with diabetes mellitus.

We present a 58-year-old man with hyperglycemic subcoma. His blood glucose level was 1,163 mg/100 ml on admission and the data of the coagulate system revealed abnormalities in the prothrombin time, fibrinogen and serum fibrin degradation products. Continuous intravenous insulin infusion therapy (CIII) was performed, and a satisfactory recovery of consciousness level and blood glucose level were obtained. Further examination revealed the patient had Crohn's disease (CD) associated with IgG and IgM anticardiolipin antibodies (aCLs). The patient was treated with corticosteroid hormones and salazosulfapyridine, and the abnormalities in the coagulate system returned to the normal range and aCLs eventually disappeared. It was speculated that in such a case, anticardiolipin antibody may play a role in the pathogenesis of CD.

Anti-Inflammatory Agents↗

Regional vascular effects of MPC-1304, a novel dihydropyridine derivative, in conscious normotensive and spontaneously hypertensive rats.

The purpose of this study was to compare the regional vascular effect of a novel dihydropyridine derivative, MPC-1304 [(+/-)- methyl-2-oxopropyl-1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3, 5-pyridinedicarboxylate], with that of nifedipine and manidipine in conscious spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The radioactive microsphere technique was used to measure systemic and regional hemodynamic parameters before and 1 hr after p.o. administration of drugs. In SHR, MPC-1304 at a dose of 1 mg/kg reduced the mean blood pressure and systemic vascular resistance and increased cardiac output, as did nifedipine (10 mg/kg) and manidipine (3 mg/kg). MPC-1304, as well as nifedipine, significantly increased the blood flow in pulmonary, gastric, small intestinal and skeletal muscular beds and reduced their vascular resistance. Manidipine increased regional blood flow only in small intestinal and skeletal muscular beds. Only MPC-1304 increased the renal blood flow. In WKY, MPC-1304 and nifedipine reduced the mean blood pressure and systemic vascular resistance to lesser degrees than in SHR. Both drugs significantly increased coronary and skeletal muscular blood flow. MPC-1304 significantly reduced the renal blood flow without altering renal vascular resistance, in striking contrast to its renal effect in SHR. These findings suggest that MPC-1304 possesses a genetic hypertension-dependent renal vasodilating action, unlike nifedipine and manidipine. One possible mechanism for this difference in the effect on renal circulation between SHR and WKY may involve the potent antagonizing effects of MPC-1304 on alpha-2 adrenoceptor-mediated vasoconstriction.

Animals↗

Cardiovascular effects of NT-1, a new patch form of nitroglycerin, alone and in combination with nifedipine in conscious dogs.

The cardiovascular effects of NT-1, a new patch form of nitroglycerin, alone and in combination with nifedipine in conscious dogs were examined. NT-1 (2.5 mg kg-1 nitroglycerin) decreased systolic blood pressure by 10-15%, while diastolic blood pressure and heart rate were not affected. Coronary blood flow and calculated rate-pressure product were decreased. These parameter changes occurred at 30 min after NT-1 application and remained constant for 8 h until NT-1 was removed. After administration of NT-1 in combination with nifedipine, systolic blood pressure was significantly decreased to a greater extent, and heart rate and coronary blood flow showed a tendency to increase compared with nifedipine alone. Rate-pressure product was not changed compared with that obtained on administration of nifedipine alone. These results suggest that NT-1 may be applicable as a transdermal sustained release medication, and show that in combination with nifedipine, NT-1 can induce a large increase in coronary blood flow without further increasing rate-pressure product.

Administration, Cutaneous↗

Platelet activation is not involved in acceleration of the coagulation system in acute cardioembolic stroke with nonvalvular atrial fibrillation.

BACKGROUND AND PURPOSE: It is generally accepted that the coagulation system is activated in ischemic stroke and that platelet activation is involved in the pathogenesis of this disease. However, little is known about how and to what extent platelet activity participates in coagulation system enhancement. We evaluated the hemostatic condition, especially with regard to platelet function and the coagulation system, within 3 days of onset of acute stroke. The study participants were limited to elderly patients with cardioembolic stroke due to nonvalvular atrial fibrillation. METHODS: Seventeen elderly patients with acute cardioembolic stroke due to nonvalvular atrial fibrillation were investigated. Within 3 days of stroke onset, beta-thromboglobulin (BTG), platelet factor 4 (PF4), thrombin-antithrombin III complex (TAT), and D-dimer from arterial blood were carefully evaluated in these patients. Blood samples from 19 healthy age- and sex-matched control subjects were also examined. RESULTS: The two studied markers of platelet activity did not change in the patients or the control subjects, and the between-group differences between the stroke and control groups were not statistically significant (BTG, 43.8 versus 31.9 ng/mL; PF4, 9.06 versus 5.78 ng/mL; respectively). In contrast, the two studied coagulation-system indicators were markedly elevated in the patients compared with the control subjects (TAT, 13.8 versus 3.5 ng/mL, P < .01; D-dimer, 366.3 versus 147.2 ng/mL, P < .01; respectively). CONCLUSIONS: Platelet function was not enhanced in the acute stage of cardioembolic stroke with nonvalvular atrial fibrillation. This result indicates that enhancement of the coagulation system in cardioembolic stroke is not the result of platelet hyperfunction, ie, "platelet-fibrin" thrombi, but rather of "stasis-related" thrombi formation.

Aged↗

Radiofrequency catheter ablation for the treatment of common atrial flutter in humans.

Endocardial catheter ablation has been recently been proposed for the treatment of arrhythmias originating in the right atrium. In this study, we used this technique in 5 patients with paroxysmal common atrial flutter and 3 patients with paroxysmal uncommon atrial flutter. Various antiarrhythmic agents had failed to prevent the recurrence of these episodes. In each procedure, we used a large-tip 7 F quadripolar catheter electrode that was introduced via the femoral vein into the lower part of the right atrium. The two distal electrodes were used to record double-spike potentials or fragmented electrograms. A unipolar electrogram recording from a distal electrode of the same catheter was also used to identify local activation. The targets for ablation were sites which showed double-spike potential and fragmented electrogram 40-60 msec earlier than the onset of the F wave. Application of radiofrequency (RF) energy (25-40 watts) (3-17 applications) terminated atrial flutter and prevented reinduction of atrial flutter in the 5 patients with common atrial flutter. However, atrial flutter could not be terminated with the application of RF energy in the 3 patients with uncommon atrial flutter. The sites at which ablation was successful were located inferior or posterior to the coronary sinus ostium between the inferior vena cava and the tricuspid valve annulus, and were characterized by double-spike potentials and fragmented electrograms with activation times > or = 40 msec before the onset of the F wave. This area may represent the exit site from the area of slow conduction, since pacing from this site showed concealed entrainment of the F wave, and a local electrogram to the onset of the F wave coincided with the pacing spike to the onset of the F wave. Follow-up of these 5 patients (19.4 +/- 10.4 weeks) revealed recurrence of the original atrial flutter in 1 patient and a new type of atrial flutter in 1 patient. The other 3 patients have been episode-free, although an antiarrythmic agent was given for the treatment of paroxysmal atrial fibrillation in 2 patients. We conclude that the application of RF energy to the presumed critical area in the atrial flutter reentrant circuit seems to be effective in terminating and preventing common atrial flutter. Long-term follow-up is required for the recurrence of atrial flutter.

Adolescent↗

A method for the re-isolation of an autonomously replicating plasmid from Aspergillus transformants.

An autonomously replicating plasmid is expected to increase the frequency of Aspergillus transformation. To construct this type of plasmid, we developed a rapid method of re-isolating autonomously replicating plasmids from Aspergillus transformants. Transformants grown in MM medium under selective pressure for 1-2 days were converted to protoplasts with a cell wall lytic enzyme (e.g. Yatalase). The protoplasts were lysed with phenol/chloroform followed by precipitation with ethanol. The total DNA was treated with RNaseA, re-precipitated with PEG, and then used to transform E. coli. These re-isolated plasmids were mainly the plasmid monomer.

Aspergillus↗

Effects of atrioventricular intervals on right atrial monophasic action potential duration during pacing or reciprocating tachycardia.

We evaluated the relationship between changes in the atrioventricular (AV) intervals and right atrial monophasic action potential duration at 90% repolarization (RA-MAPD90) in humans. In 4 patients, RA-MAPD90 was measured during AV reciprocating tachycardia (AVRT, n = 2) or AV node reentrant tachycardia (AVNRT, n = 2) and atrial or ventricular pacing at similar cycle lengths. In 10 patients, RA-MAPD90 was measured during continuous atrioventricular sequential pacing at AV intervals of 0, 50, 100, 150, 200, 250, 300, 350 msec for 90 sec at a cycle length of 333-400 msec. In patients with AVRT, the RA-MAPD90 during tachycardia was shorter than RA-MAPD90 during RA or RV pacing. In patients with AVNRT, RA-MAPD90 during tachycardia was similar or longer than RA-MAPD90 during RA or RV pacing. As the AV interval was increased from 0 msec to 150 msec, the peak right atrial pressure decreased from 8-12 mmHg to 2-3 mmHg. RA-MAPD90 decreased to its minimal value at an AV interval of 150 msec. The maximal difference in the RA-MAPD90 obtained by changing the AV interval was 22.5 +/- 3.0 msec. We conclude that 1) a very short AV or VA interval causes an increase in RA-MAPD90 which correlates with an increase in RA pressure, and 2) RA-MAPD90 during supraventricular tachycardia is different from RA-MAPD90 during atrial or ventricular pacing. Thus, a contraction-excitation feedback mechanism may exist in the human atrium.

Action Potentials↗

A region of the muscarinic-gated atrial K+ channel critical for activation by G protein beta gamma subunits.

Complementary DNAs encoding two types of inwardly rectifying K+ channels, GIRK1 and IRK1, have been cloned from rat atrium and mouse macrophage, respectively. GIRK1 expressed in Xenopus oocytes was activated by acetylcholine when m2 muscarinic acetylcholine receptor was coexpressed. The acetylcholine-induced activation of GIRK1 was enhanced by coexpression with the G protein beta 1 gamma 2 subunit but not the beta 1 gamma 1 or alpha subunits. Deletion of the C-terminus of GIRK1 impaired the channel activation associated with the beta 1 gamma 2 subunit. Moreover, replacement of the C-terminus of IRK1 with that of GIRK1 produced a chimera channel that was activated by the beta 1 gamma 2 subunit, whereas intact IRK1 was not activated by the beta 1 gamma 2 subunit. These findings define the C-terminus of GIRK1 as a regulatory region for the G protein beta gamma subunit.

Animals↗

Inhibitory effect of perindopril, a novel angiotensin-converting enzyme inhibitor, on neointima formation after balloon injury in rats and cholesterol-fed rabbits.

We investigated the effect of perindopril, a novel angiotensin-converting enzyme (ACE) inhibitor, on neointima formation in vessel walls after balloon injury in rats (carotid artery) and cholesterol-fed rabbits (thoracic aorta). Continuous treatment with perindopril significantly reduced neointima formation in both species, as compared with the control group: intima/media (I/M) ratio (rats -62%; p < 0.001; rabbits -25%, p < 0.05); neointima area (rats -65%, p < 0.01; rabbits -24%, p < 0.05). These changes involved reduction of intimal smooth muscle cells (SMC) in rats and of macrophages in rabbits. Furthermore, perindopril also significantly decreased ACE activity in both aortic tissue and serum [11.38 +/- 0.87 vs. 34.93 +/- 6.44 pmol His-Leu (HL)/mg/min (p < 0.01) and 2.79 +/- 0.28 vs. 38.50 +/- 5.41 pmol HL/mg/min (p < 0.001), respectively], aortic contraction evoked by angiotensin I (AI) and mean blood pressure (BP, 84.9 +/- 3.5 vs. 109.3 +/- 3.8 mm Hg, p < 0.001) as compared with control values. These results indicate that perindopril may reduce neointima formation by suppressing the aortic renin-angiotensin system (RAS). These findings indicate that perindopril may be capable of preventing restenotic lesions after angioplasty in humans [corrected].

Angioplasty, Balloon↗

Transformation of intact Aspergillus niger by electroporation.

A new rapid transformation system for Aspergillus niger that uses electroporation to render intact germinating conidia permeable to DNA is described. The transformant colonies appeared earlier than transformants obtained by the protoplast-forming method. Without pretreatment of the conidia the transformation frequencies were 1.2 colonies per micrograms of integrative vector and 100 colonies per micrograms of plasmid DNA. When the conidia were treated with a dilute solution of fungal cell wall lytic enzyme, the frequency of transformation was increased by approx. 2-fold when using two vectors. Southern blot analysis of genomic DNA and restriction endonuclease-digested DNA from a random sample of transformants showed homologous and nonhomologous integration of the integrative vector into the genome, as is also observed with the protoplast-forming method. In transformation with the plasmid vector, the transformant DNA was shown to be mostly maintained in free form with minimal integration into the chromosome when transformed by either intact electroporation or the conventional method.

Aspergillus niger↗

[Very low-intensity anticoagulant therapy in elderly cardioembolic stroke patients with nonvalvular atrial fibrillation].

Several investigations revealed the significant effect of anticoagulant therapy for stroke prevention in patients with atrial fibrillation. However, in the elderly population, the optimal therapeutic strategy of secondary prevention of cardioembolic stroke is still controversial. We prospectively evaluated the efficacy and safety of very low-intensity anticoagulant therapy (target range, Thrombotest = 20-30%: INR = 1.47-1.81) for elderly cardioembolic stroke patients due to nonvalvular atrial fibrillation. Twenty cardioembolic stroke patients (average age 80.0) with nonvalvular atrial fibrillation were included in our study. Anticoagulant therapy began 5 of 7 days after the embolic event. The incidental rate of ischemic stroke recurrence and bleeding complication were evaluated. During mean follow-up of 14.7 month, the annual recurrent rate of ischemic stroke was 8.2% (cardioembolic stroke = 4.1%/year, atherothrombotic stroke = 0%/year, lacunar stroke = 4.1%/year), whereas one non-fatal gastrointestinal bleeding was observed. Our study suggested that even in the elderly population, very low-intensity anticoagulant therapy may be effective, and safe with respect to prevention of bleeding complications, for secondary cardioembolic stroke prevention.

Aged↗

Thielocin B3, a novel antiinflammatory human group II phospholipase A2 specific inhibitor from ascomycetes.

Evidence accumulated to date suggests that extracellular group II phospholipase A2 (PLA2-II) is involved in the pathogenesis of inflammatory disease. During screening for PLA2 inhibitors, we found a novel PLA2 inhibitor named thielocin B3 in the culture broth of an ascomycetes. Thielocin B3 strongly inhibited human PLA2-II (IC50 = 0.076 microM) in a reversible and noncompetitive manner (Ki = 0.098 microM), whereas it inhibited human group I PLA2 only weakly (IC50 = 18 microM). It also quenched the tryptophan fluorescence of Naja mocambique venom PLA2; almost 100% quenching being attained at a thielocin B3/enzyme molar ratio of 1.0. Its inhibitory activity toward human PLA2-II and Naja mocambique PLA2 was markedly decreased by methylation of its two carboxyl groups, while the quenching observed for Naja mocambique PLA2 was not altered. These results suggest that the two carboxyl groups do not participate in the binding of thielocin B3 to the enzyme, but play a crucial role in the PLA2 inhibition. Furthermore, in the rat carrageenan-induced pleurisy model, thielocin B3 significantly reduced both exudate volume and PLA2 activity in the exudate when coinjected with carrageenan.

Animals↗

MPC-1304, another type of dihydropyridine, possessing highly potent vasodilating action.

We investigated the vasodilating action of MPC-1304, one of the most potent dihydropyridines causing hypotension, in anesthetized dogs and compared this with its binding properties. After intraarterial injection, MPC-1304 was 3 times less potent than other dihydropyridines (nitrendipine, nifedipine, nicardipine and nisoldipine) in increasing femoral blood flow. After infusion of these drugs, however, MPC-1304 was the most potent in increasing femoral blood flow. The onset and recovery of the effect of MPC-1304 on femoral blood flow were slower than for nifedipine. Higher doses of Bay K 8644 were needed to antagonize the stimulating activity of MPC-1304 than for nifedipine. In a competition assay of [3H]nitrendipine binding, MPC-1304 and its metabolites bound to the dihydropyridine receptor with lower affinity than the other dihydropyridines. The binding affinity of [3H]MPC-1304 was lower than that of [3H]nitrendipine, consistent with the potency of this drug to increase femoral blood flow by bolus injection. The association and dissociation of [3H]MPC-1304 was slower than those of [3H]nitrendipine, which is consistent with the slow onset and long-lasting vasodilating effects of MPC-1304 on femoral blood flow. Moreover, diltiazem reduced a part of [3H]MPC-1304 binding in a competitive manner. In ex vivo binding assays with serum and aorta obtained after oral administration of the drug in spontaneously hypertensive rats, MPC-1304 inhibited [3H]nitrendipine binding to membrane preparations less potently than nifedipine. From these results, we conclude that MPC-1304 is a different type of dihydropyridine possessing the most potent vasodilating action of the representative dihydropyridines tested. Its activity cannot be explained solely by a slow interaction with voltage-dependent Ca2+ channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Cardiovascular profile of MPC-1304, a novel dihydropyridine calcium antagonist: comparison with other calcium antagonists.

The cardiovascular profile of a novel calcium antagonist, MPC-1304 and its active metabolites were investigated in experimental animals in vitro and in vivo, and were compared with those of other calcium antagonists or nitroglycerin (NTG). The ratio of negative chronotropic/negative inotropic effect of MPC-1304 was 23 times higher than that of nifedipine in paced left and spontaneously beating right atria of guinea pigs. MPC-1304 and nifedipine did not change atrial-His (AH) conduction time or His-ventricular (HV) conduction time at hypotensive doses in open-chest dogs, whereas diltiazem prolonged AH time. MPC-1304 increased coronary blood flow, and strongly decreased myocardial oxygen consumption (MVO2) by decreasing blood pressure (BP) and heart rate (HR) in open-chest dogs. Left ventricular pressure (LVP) was not changed. Contractile force (dp/dt) was slightly increased by its action on afterload. MPC-1304 and nifedipine did not dilate the large coronary artery, but NTG did. MPC-1304 increased blood flow of the peripheral arteries, especially vertebral and CBF in anesthetized dogs. Cerebral blood flow (CBF) also increased. MPC-1304 decreased serum cholesterol levels and the plaque area of the aorta in cholesterol-fed rabbits. Because of this cardiovascular profile, MPC-1304 should be useful in treatment of hypertension as well as angina pectoris.

Animals↗