[A case of hypereosinophilic endomyocarditis with a benign clinical course: a case report and review of 25 cases with the syndrome in Japan].
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Biomedical subjects
Publications and source records attributed to M Sekiguchi.
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Whether giant negative T waves (GNT) of 1 mV or greater represent the electrocardiographic characteristics of idiopathic cardiomyopathy, particularly apical hypertrophic cardiomyopathy, is controversial. To clarify this point, a comparative study was conducted for 57 persons with GNT (GNT+ group) and 57 persons of hypertrophic cardiomyopathy with either asymmetric septal hypertrophy or diffuse hypertrophy of the ventricular wall in the absence of GNT (GNT- group). Patients with cerebral vascular accidents, myocardial infarctions, valvular heart disease, myopericarditis, and implanted pacemakers were excluded from the study because these patients' ECGs may show GNT. Left ventriculograms were investigated at end-diastole in the right anterior oblique projection. The GNT+ group showed a spade-like configuration indicating a marked reduction in the lumen of the apical cavity in 25 cases (43.9%); a kidney or banana-like configuration indicating the inferior wall bulging into the left ventricular cavity in its mid-zone in eight cases (14.0%), and an oval configuration which indicated no deformity of the left ventricular cavity in 24 (42.1%). The spade-like configuration was also seen in four cases (7.0%) of the GNT- group. A study of ventricular wall thicknesses based on left ventriculography showed that 25.5% of cases with GNT did not have concomitant apical hypertrophy. Generally, the GNT+ group cases had a significantly thicker anterior left ventricular wall and apical hypertrophy compared to the GNT- group. The hypertrophic states of the apical wall and anterior wall of the left ventricle correlated well. The GNT+ group included a significantly larger percentage of patients who were middle aged and older than did the GNT- group, and the frequency of accompanying hypertension was significantly higher in the former. The confirmed or suspected familial occurrence of cardiomyopathy (CM) was observed in 32 cases (56.1%) of the GNT- group, and in 18 cases (31.6%) of the GNT+ group, i.e., the incidence was significantly lower in the GNT+ group. In an endomyocardial biopsy study, 40 cases (70.1%) of HCM without GNT had bizarre myocardial hypertrophy with disorganization (BMHD). The incidence of BMHD in the GNT+ group was 21/57 (36.8%)-significantly lower than in the GNT- group. In the GNT- group, there was no significant difference in the incidence of BMHD between relatively young and old patients or between patients with and without accompanying hypertension; whereas, in the GNT+ group, it was significantly lower among those with accompanying hypertension and in older patients than in those without accompanying hypertension and in younger patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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Nucleotide sequence of a DNA fragment containing the alkA gene and its control region has been determined using a chemical method. Only one open reading frame responsible for 3-methyladenine DNA glycosylase II was found. The hypothetical polypeptide deduced from the DNA sequence, with a molecular weight of 31,400, has an amino-terminal sequence and total amino acid composition identical to that of purified 3-methyladenine DNA glycosylase II. We constructed hybrid plasmids carrying an alkA'-lacZ' fusion, with the proper control region for alkA expression. A hybrid polypeptide with beta-galactosidase activity was formed when lac mutant cells harboring such plasmids were incubated with low doses of N-methyl-N'-nitro-N-nitrosoguanidine or methylmethane sulfonate. Other DNA-damaging agents, such as ethylmethane sulfonate, nalidixic acid, and ultraviolet light did not induce the enzyme activity. The induction was controlled by the ada and adc, but not by the recA and lexA genes.
By in vitro recombination we have constructed hybrid plasmids which can suppress the increased methylmethane sulfonate sensitivity caused by the alkA1 mutation in Escherichia coli. Since the cloned DNA fragment was mapped at 44 to 45 min of the E. coli K12 genetic map, an area where the alkA gene is located, we conclude that the cloned DNA fragment contains the alkA gene itself but not other gene(s) that suppresses the alkA mutation. Specific labeling of plasmid-encoded proteins by the maxicell method revealed that the alkA codes for a polypeptide whose molecular weight is about 30,000. When cells harboring the alkA+ plasmids were grown in the presence of low doses of a simple alkylating agent (adapted condition), the activity of 3-methyladenine DNA glycosylase II was increased. The enzyme activity was copurified with the Mr 30,000 polypeptide. These results indicate that the alkA gene codes for 3-methyladenine DNA glycosylase II. Taking advantage of overproduction of the alkA protein in adapted cells that harbor multicopy plasmids carrying the alkA+ gene, 3-methyladenine DNA glycosylase II has been purified to apparent physical homogeneity.
To identify proteins concerned with chromosome condensation processes, we used a temperature-sensitive mutant, tsBN2 derived from BHK21, in which premature chromosome condensation occurred at high temperature. When the proteins synthesized in tsBN2 during the induction of premature chromosome condensation were analyzed by two-dimensional gel electrophoresis, we found that an acidic protein with a molecular weight of 35,000 was specifically associated with chromosome condensation. In the normal cell cycle, this protein was synthesized from the G2 through the M phase. The protein was located mainly in the chromosome fraction and was phosphorylated.
Taking advantage of overproduction of the uvrD protein in cells that harbor multicopy plasmids carrying the uvrD gene, we have purified protein to physical homogeneity. The purified protein possesses single-stranded DNA-dependent ATPase and ATP-dependent DNA unwinding activities, and both activities are equally inactivated by antibodies raised against DNA helicase II. Molecular weight (75,000) and chromatographic properties of the uvrD protein are also similar to those of DNA helicase II and DNA-dependent ATPase I (Richet, E., and Kohiyama, M. (1976) J. Biol. Chem. 251, 808-812; Abdel-Monem, M., Dürwald, H., and Hoffmann-Berling, H. (1977) Eur. J. Biochem. 79, 39-45). Thus, it is concluded that the uvrD protein is identical with DNA helicase II and DNA-dependent ATPase I. Expression of the uvrD gene, as assayed by DNA-dependent ATPase activity, was stimulated by exposure of bacteria to nalidixic acid or mitomycin C. No increase in ATPase activity was observed with recA mutant cells, although basic levels of DNA-dependent ATPase activity in recA+ and recA- strains were almost the same. Thus, the uvrD gene is constitutively expressed but also regulated in a recA-dependent fashion.
Mutants of Escherichia coli completely deficient in RNase H activity were isolated by inserting transposon Tn3 into the structural gene for RNase H, rnh, and its promoter. These rnh- mutants exhibited the following phenotypes; (1) the mutants grew fairly normally, (2) rnh- cells could be transformed with ColE1 derivative plasmids, pBR322 and pML21, though the plasmids were relatively unstable, under non selective conditions, (3) rnh- mutations partially suppressed the temperature-sensitive phenotype of plasmid pSC301, a DNA replication initiation mutant derived from pSC101, (4) rnh- mutations suppressed the temperature-sensitive growth character of dnaAts mutant, (5) rnh- cells showed continued DNA synthesis in the presence of chloramphenicol (stable DNA replication). Based on these findings we propose a model for a role of RNase H in the initiation of chromosomal DNA replication. We suggest that two types of RNA primers for initiation of DNA replication are synthesized in a dnaA/oriC-dependent and -independent manner and that only the dnaA/oriC-dependent primer is involved in the normal DNA replication since the dnaA/oriC independent primer is selectively degraded by RNase H.
The cytotoxic effect of prostaglandin (PG) D2, PGE1 and PGF2 alpha was examined on human osteosarcoma cells (KSu cell line) in vitro, and PGD2 was most effective. DNA, RNA and protein syntheses of KSu cells were also found to be inhibited by PGD2 at a concentration of 5 micrograms/ml. Furthermore, the proliferation of various human malignant tumor cells was inhibited by PGD2 without exception so far. These results suggest that PGD2 shows an anti-neoplastic effect on a variety of human malignant tumor cells.
Detergent-resistant phospholipase A (DR-phospholipase A) of E. coli is a 28K-dalton protein and is exclusively located in the outer membrane. We cloned the pldA gene of E. coli, which is responsible for the activity of DR-phospholipase A. Strains bearing the plasmid which contained the pldA gene yielded a large amount of the outer membrane protein with a molecular weight of about 28K daltons and overproduced 20 to 65 times as much DR-phospholipase A activity as the wild type strain. Experiments with minicells and maxicells revealed that the pldA-containing plasmid was coding for a 28K protein. These results strongly indicated that pldA is the structural gene for DR-phospholipase A. There was apparently no difference with respect to the association of the enzyme with the envelope fraction between the overproducer and the wild type strain. The overproduced enzyme was properly transported to the outer membrane. Neither the growth rate nor the phospholipid composition of the overproducer was remarkably different from in the wild type strain. Thus, the overproduction of DR-phospholipase A apparently caused no phenotypic variations. E. coli has very excessive ability to transport and integrate the outer membrane protein.
The nucleotide sequence of the pldA gene of Escherichia coli K-12, which codes for detergent-resistant phospholipase A (DR-phospholipase A), located in the outer membrane, was determined and the amino acid sequence of DR-phospholipase A was deduced. DR-phospholipase A contains 269 amino acids, resulting in a protein with a molecular weight of 30,809. It does not contain any cysteine residues and seems to be synthesized first as a precursor with a typical signal peptide composed of 20 amino acids. The NH2-terminus of the mature protein is glutamine, a polar amino acid, while other outer membrane proteins so far determined have a nonpolar amino acid there. The hydropathy profile of the deduced amino acid sequence of DR-phospholipase A was studied. Most of the region was rather hydrophilic and there were no stretches of hydrophobic amino acids. Computer analysis showed that there are no homologies between DR-phospholipase A and other extracellular phospholipases whose amino acid sequences are known. The candidates for the promoter region of the pldA gene, the 5'-flanking region, have a significantly high AT content, while the AT content of the coding region is about the same as the average AT content of the E. coli chromosome. A typical rho-independent transcription termination site is also present at the 3'-flanking region. This is the first example of the primary structure of a membrane-bound phospholipase.
Serial endomyocardial biopsy findings in 20 cases with acute myocarditis of possible viral origin were analyzed. The histopathological findings were analyzed during the acute (0-10 days after the onset: 8.3 +/- 1.9 days; 6 cases), the subacute (11-21 days: 18.2 +/- 2.2 days, 6 cases), and the convalescent stages (22-167 days: 54.5 +/- 45.4 days; 8 cases). The incidence and severity of various changes of the cardiac myocytes and interstitial changes were analyzed and compared at each stage of the disease. In the acute stage, interstitial cell infiltrations were composed of fibroblasts, macrophages and lymphocytes, taken out in descending order. In the convalescent stage, interstitial cell infiltration showed a marked increase and was replaced by fibrocytes. In the subacute stage, transitional changes between the acute and convalescent stages were observable. A controlled myocardium in 21 cases with myocardial infarction which were compared at various stages revealed that in the acute stage, neutrophils were most prominent, and in the subacute and convalescent stages, macrophages were most prominent and plasma cells were most often observed. The time course changes of the histopathological findings in acute myocarditis were as follows: In the acute stage, Interstitial cell infiltration which is composed of fibroblasts, macrophages and lymphocytes, fragmentation of the muscle bundles, myocytolytic changes, swelling and scarcity of the cytoplasm and swelling of nuclei, variation in size of the myocytes, disarrangement of the muscle bundles, interstitial edema, increased glycogen deposition in the myocytes, abnormal branching of the myocytes, and interstitial fibrosis were observable. In the convalescent stage, most of the above described findings were still observable except for the myocytolytic change, swelling of myocytes and interstitial edema.(ABSTRACT TRUNCATED AT 250 WORDS)
In a series of studies with endomyocardial biopsy, 7 adult cases with cardiac disease and eosinophilia were studied clinically and electro-microscopy. Degranulation of the eosinophils in the peripheral blood was observed ultrastructurally in 3 of the 4 cases studied. The clinical expression of the 7 patients were, restrictive cardiomyopathy in 2, dilated cardiomyopathy in 2 and sick sinus syndrome in 1 and others in 2. Endocardial thickening was observed in 5 cases, one of whom showed a marked cellular infiltration with macrophages, plasma cells, lymphocytes and mast cells. One other case showed cell debris of degranulated eosinophils. Degeneration of the myocytes was manifested by an increase in Z-bands of the myofibrils as well as streaming (1 case), disarrangement of the myofibrils, and mitochondrial change (1 case) which was characterized by giant mitochondria (1 case) as well as by a numerical increase in mitochondria. Increase of atrial granules and mitochondria in a right atrial biopsy of a case with sick sinus syndrome was noteworthy. Basal lamina layering of the capillaries of the myocardium and pyknosis of an endothelial cell cytoplasm were also noted in each case. These observations may reveal that various disease processes are taking place in the endocardium and adjacent myocardium.
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