Myocardial perfusion in patients with left bundle branch block and without coronary artery disease]

For the evaluation of myocardial perfusion in patients with left bundle branch block (LBBB), we performed exercise stress (Ex)-redistribution (RD) myocardial tomography with thallium-201 (201Tl) in 23 patients with LBBB and without coronary artery disease (CAD). Myocardial images in patients with LBBB were compared with those of 9 patients with CAD who showed Ex induced transient septal defect. Bull'-eye maps (201Tl distribution maps at Ex and RD and 201Tl washout rate [WOR] map) were made from myocardial tomograms. In 23 patients with LBBB, 15 patients (65%) developed myocardial perfusion abnormality. In 10 (67%) of these 15 patients, transient perfusion defect appeared in the entire septum (diffuse type). On the other hand in 5 patients (33%), localized fixed perfusion defect developed at the boundary between septum and anterior wall (focal type). In focal type, every patient had other disease such as hypertension, aortic stenosis or sick sinus syndrome. While in patients with diffuse type, other diseases were observed in 30% (p less than 0.05) and they were limited to hypertension or diabetes mellitus. These facts suggested that mechanisms of perfusion abnormalities might be different between these two groups. We compared the perfusion abnormality between LBBB diffuse type and CAD. The extent of the defects was not different between two groups. Although apex was included within the defect in 89% of CAD population, apical defect was observed in only 20% of diffuse type (p less than 0.05). Minimal 201Tl WOR and 201Tl uptake ratio of septum to lateral wall indicated that exercise induced septal defect was slighter in diffuse type than CAD.(ABSTRACT TRUNCATED AT 250 WORDS)     

Significance of deposits and abnormalities of the glomerular basement membrane in tissue injury accompanying IgA nephropathy.

The glomerular injuries in 129 cases of IgA nephropathy (IgA-N) were examined ultrastructurally with special reference to the glomerular basement membrane (GBM) deposits and capillary loop abnormalities, and the correlation between these findings and the clinicopathological data was analyzed. The following results were obtained. 1) The degree of daily excretion of urine protein (UP) and creatinine clearance (Ccr) revealed a significant correlation with the degree of mesangial hypercellularities and the frequency of segmental lesions. 2) All sites of GBM deposits, and discontinuity and/or splitting among the GBM abnormalities showed a significant relation to the severity of proliferation and segmental lesions. 3) The GBM deposits, discontinuity and splitting showed a significant relation to the degree of UP and Ccr. We speculate therefore that capillary loop deposits and/or capillary loop discontinuity and splitting could represent histological prognostic factors for an unfavorable outcome in IgA nephropathy.     

Pulmonary injury by an over-the-counter drug, Nospole G]

A 78-year-old woman was admitted with dyspnea. She had caught a cold and took an over-the-counter drug (Nospole G) for 2 weeks before admission. Chest radiography and CT scanning showed bilateral diffuse and interstitial shadows, and arterial blood gas analysis demonstrated severe hypoxemia. Withdrawal of Nospole and treatment with both corticosteroid and sivelestat sodium resulted in improvement of clinical findings and successful recovery from mechanical ventilation. A drug lymphocyte stimulation test for Nospole G was positive. Based on these findings, we determined that this patient had drug-induced pneumonitis caused by Nospole G. Finally, she died of sepsis caused by multidrug-resistant Staphylococcus aureus (MRSA) infection. In summary, we report here an elderly case of drug-induced pneumonitis successfully weaned from mechanical ventilation by early treatment with corticosteroid and sivelestat sodium, monitored by changes of markers for interstitial pneumonitis (KL-6, SP-A, SP-D).     

Immunohistochemical Detection of Porcine Teschovirus Antigen in the Formalin‐fixed Paraffin‐embedded Specimens from Pigs Experimentally Infected with Porcine Teschovirus

Porcine teschovirus (PTV) antigens were detected by a streptavidin‐biotin complex method in formalin‐fixed paraffin‐embedded tissues of 3‐week‐old pigs that had been inoculated intravenously with PTV Talfan strain. PTV antigens were detected in cytoplasm of nerve cells, glial cells and endothelial cells in the cerebellar nuclei, the grey matter of the midbrain, pons and medulla oblongata and the ventral horn of the spinal cord and of ganglion cells in the spinal ganglion corresponding to those lesions characterized as non‐suppurative encephalomyelitis and ganglionitis. The results of this study suggest that nerve cells of the brain stem and spinal cord and ganglion cells of the spinal ganglion permit PTV replication and represent the main target cell population of PTV. This is the first study to demonstrate PTV antigen by immunohistochemistry in formalin‐fixed paraffin‐embedded tissue specimens from pigs infected with PTV.     

Neuromuscular blockade following high-dose vecuronium administration

To determine the onset time, duration of action and recovery time of high-dose vecuronium, 70 patients were assigned to receive either 100, 150, 200 or 300 micrograms.kg-1 of vecuronium for muscle relaxation during elective surgery. Neuromuscular blockade was continuously quantitated by recording the EMG response to stimulation of the ulnar nerve. The onset time from the time of vecuronium administration to maximum blockade decreased from 4.6 +/- 1.1 to 2.4 +/- 0.5 min when the vecuronium doses increased from 100 to 300 micrograms.kg-1. Significant differences were observed in the onset time between the 100 micrograms.kg-1 dose and the other dose groups. Endotracheal intubating conditions were excellent in all patients except 3 in the 100 micrograms.kg-1 dose group. The duration of action from the time of injection to 25% recovery increased from 32 +/- 9 to 138 +/- 48 min in a dose dependent manner. The duration of action after increment doses of 40 or 50 micrograms.kg-1 up to 25% recovery of T1 did not vary significantly within the same dose group. With an initial dose of 150 micrograms.kg-1 and subsequent increment doses of 50 micrograms.kg-1 or less, the duration of action remained constant. The recovery time from 25 to 75% recovery was within 11 minutes when antagonists were administered. High-dose vecuronium may, therefore, be a useful alternative to SCC, when a rapid onset is required and to pancuronium, when a rapid recovery from neuromuscular blockade is requested.     

A new myeloblastic leukemia cell line with double minute chromosomes. Induction of methotrexate resistance and dihydrofolate reductase gene amplification.

To test the relationship between DMs and drug resistance in newly established AML cell lines, KY821, and its clone KY821A3, the latter had lost DMs during cloning, were cultured in increasing concentrations of MTX. KY821 became resistant against 2 x 10(-4) M MTX, whereas KY821A3 did against 2 x 10(-5) M MTX in a same period. Enhanced enzyme activities of DHFR were correspondent to the increased DMs numbers and DHFR gene amplification in both resistant clones. The amplified DHFR gene was located on DMs by in situ hybridization. These data indicated that the presence of DMs in KY821 would facilitate the acquisition of drug resistance.     

Clinical studies on cefteram pivoxil granules in pediatrics

A newly developed cephalosporin, cefteram pivoxil (CFTM-PI, T-2588), was evaluated clinically in 40 patients. A pharmacokinetic study was also performed with 8 patients. CFTM-PI was administered as granules. One patient was given CFTM-PI at a dose of 1.5 mg/kg, each of 3 patients was given the drug at a dose of 3 mg/kg and each of 4 patients at a dose of 6 mg/kg. In most cases, serum concentrations of CFTM were determined at 2, 3, 4, and 6 hours after dosing. Urinary concentrations of CFTM were measured for urinary samples collected during periods of 0-2, 2-4, 4-6 and 6-8 hours after dosing. CFTM was assayed using the disk or the cup method using Klebsiella pneumoniae ATCC 10031 as the test organism. The clinical evaluation was conducted in 40 children including 13 patients of acute tonsillitis, 10 of acute lacunar tonsillitis, 10 of scarlet fever, 2 of acute bronchitis, 2 of pneumonia, and 1 each of pneumonia with enteritis, phlegmon and urinary tract infection. The patients were from 4 months to 13 years old. Daily doses were from 8.7 to 12 mg/kg. After CFTM-PI administration in doses 1.5 mg/kg, 3 mg/kg and 6 mg/kg, peak serum concentrations of CFTM were 0.38 microgram/ml, 0.73-2.25 micrograms/ml and 1.2-2.9 micrograms/ml, respectively, and half-lives were 1.55, 0.95-2.30 and 0.80-2.72 hours, respectively. Urinary excretion rates up to 6 or 8 hours after dosing were 10.8-24.7%. Clinical efficacies of CFTM-PI in 40 patients were "excellent" in 27 children, "good" in 12 children and "fair" in 1 with an efficacy rate of 97.5%. Twenty seven strains of causative organisms, including 15 strains of Streptococcus pyogenes, 1 of Escherichia coli, 1 of Salmonella 04, 6 of Haemophilus influenzae, 1 of Haemophilus parainfluenzae and 3 of Branhamella catarrhalis, were isolated. After treatment all strains except 1 strain of B. catarrhalis (unchanged), Salmonella 04 (unknown) and 1 strain of H. parainfluenzae (unknown) were eradicated. Side effects observed clinically were only 1 case of diarrhea. Eosinophilia was observed in 1 case.     

Generation of functional and mature dendritic cells from cord blood and bone marrow CD34+ cells by two-step culture combined with calcium ionophore treatment

The object of this study is to explore a culture method to generate a large number of functional and mature dendritic cells (DC) from human CD34+ hematopoietic progenitor cells. In the present study, we used a two-step method combined with calcium ionophore to induce DC from cord blood (CB) or normal human bone marrow (BM) CD34+ progenitor cells. The two-step method consists of 10 days of first step culture for the expansion and proliferation of CD34+ hematopoietic progenitor cells in the presence of SCF, IL-3, IL-6, G-CSF, and 7--11 days of second step culture for the induction of DC in the presence of GM-CSF, IL-4 and TNF-alpha. By the two-step culture, total nucleated cells were increased 208+/-66 (+/-SD, n=13), or 94+/-29 (n=5)-fold in the culture of CB or BM cells, respectively, compared with the number of CD34+ cells at the time of starting culture. Out of the total nucleated cells, 23 +/-10.4% of cells in CB cell culture and 25 +/-5% of cells in the BM cell culture acquired DC characteristic phenotypes, which were marked expressions of CD1a, HLA-DR, co-stimulatory molecules such as CD80, CD40, and adhesion molecule such as CD58. In allogeneic mixed leukocyte reaction (MLR), two-step cultured cells showed potent allo-stimulatory capacity. With this two-step culture, the absolute number of CD1a+ cells that co-expressed HLA-DR, CD80, CD40 and CD58 was enhanced approximately 3 times in CB cell culture and 1.9 times in BM cell culture, compared with the commonly used one-step culture method for the generation of DC from CD34+ cells using SCF, GM-CSF and TNF-alpha. However, on these DC generated in the two-step culture, the expressions of co-stimulatory molecule CD86 and mature DC marker CD83 were not sufficient. By the treatment of two-step cultured cells with calcium ionophore agent (A23187), the expression of co-stimulatory molecules such as CD86 and CD80 (especially CD86) was up-regulated. Besides, the expression of mature DC marker CD83 was remarkably induced by treatment with A23187 for a short duration (24 h). Consistent with the up-regulation of surface molecules CD86, CD80 and CD83, the two-step cultured cells treated with A23187 also showed a stronger allo-stimulatory capacity compared with the cells without A23187 treatment. In conclusion, the present study demonstrated that the two-step culture method effectively improved the yield of CD1a+ DC generated from CD34+ cells, and the phenotypes and functions of these CD1a+ DC could be enhanced efficiently by treatment with a calcium ionophore agent.     

Anionic polymerization of fluorine-containing vinyl monomers, 12. Anionic polymerization mechanism of hexafluoro-1,3-butadiene

Initiation and propagation reaction mechanisms of the anionic polymerization of hexafluoro-1,3-butadiene (HEBD) were investigated. The initiation reaction with caesium tert-butoxide was found to be completed within 5 min although the reactions were carried out at a much lower temperature than that of the polymerization reaction. The initiation reaction was, therefore, inferred to take place in an anionic fashion by adding the tert-butoxide anion to HFBD. In order to clarify the propagation reaction mechanism of HFBD which yielded a polymer with a polyvinylene structure, the polymerization reactivity of HFBD and hexafluoro-2-butyne (HFBY), the isomerization of HFBD to HFBY, and the structural difference between poly(HFBD) and poly(HFBY) were discussed. In spite of the low yield of HFBY by the isomerization reaction under polymerization conditions, higher yields of poly(HFBD) were obtained. Judging from the X-ray analysis which showed that poly(HFBD) was highly crystalline and poly(HFBY) was amorphous, poly(HFBD) might not be produced by polymerization of HFBY. An addition reaction of the propagating anion to the carbon-2 of the HFBD monomer followed by isomerization at the propagating living end to yield poly[1,2-bis(trifluoromethyl)vinylene] is proposed.