Effect of antihypertensive therapy on blood rheology in patients with essential hypertension

Hypertension is an important risk factor for cardiovascular disease, and antihypertensive drugs can decrease the occurrence of such events in hypertensive patients. This study compared the rheological properties of blood in 22 untreated hypertensive patients, 42 patients taking antihypertensive drugs and 74 normotensive subjects. Using a microchannel method, the whole blood passage time was measured and blood movement was observed with a microscope connected to an image display unit. The blood passage time in untreated hypertensive patients was significantly higher than in treated hypertensive patients or normotensive subjects, but was similar in the latter two groups. Microscopic observations showed that platelet aggregation and leucocyte adhesion were increased in untreated hypertensive patients, resulting in poor flow, while blood samples from treated hypertensive patients and normotensive subjects passed smoothly through the microchannels. These rheological differences could contribute to the decrease in cardiovascular disease seen when hypertensive patients are treated effectively.     

Powerful activation of skeletal muscle actomyosin ATPase by goniodomin A is highly sensitive to troponin/tropomyosin complex

Goniodomin A has been shown to cause the conformational change of actin to modify actomyosin ATPase activity. Goniodomin A induced a potent stimulation of the actomyosin ATPase activities of the actin-myosin reconstituted system and natural actomyosin in the range of 10(-8) to 10(-7) M. When the concentration was increased above 10(-7) M, actomyosin ATPase activity was decreased. Interestingly, the troponin/tropomyosin complex caused a concentration-dependent inhibition of the goniodomin A-induced stimulation of actomyosin ATPase activity. In the presence of a high concentration of the troponin/tropomyosin complex, goniodomin A decreased actomyosin ATPase activity in a concentration-dependent manner. The enhancement of the ATPase activity of troponin/tropomyosin-free natural actomyosin by goniodomin A was larger than that obtained with natural actomyosin. Goniodomin A at lower concentrations enhanced the superprecipitation of natural actomyosin but decreased it at higher concentrations. The ATPase activity of skeletal muscle myofibrils and the contractile response of skinned fibers to Ca(2+) were never activated and were decreased by this compound, suggesting an inhibition by the troponin/tropomyosin complex. In the far ultraviolet circular dichroism, goniodomin A above 10(-8) M increased the negative ellipticity at 220 nm, suggesting an increase in the alpha-helical content of actin. These results suggest that goniodomin A increases and decreases actomyosin ATPase activity, probably through the stimulatory and inhibitory sites on actin, respectively. It is also suggested that the troponin/tropomyosin complex binds to actin to inhibit the goniodomin A-induced enhancement of actomyosin ATPase activity, probably by affecting the stimulatory site on the molecule.     

Renin assay using a fluorogenic substrate and high performance liquid chromatography.

Measurement of renin activity in human fluids using a fluorogenic substrate and high performance liquid chromatography (HPLC) is described. A nine amino acid peptide containing the fluorogenic residue, N-(2-pyridyl) glycine (Pg) is used as a substrate. The peptide sequence is homologous with the cleavage site of human angiotensinogen. This substrate is hydrolyzed by renin to generate fluorogenic and non-fluorogenic products. The amount of fluorogenic product is directly measured by reversed phase HPLC. Optimization of assay conditions and measurement of human serum renin levels are described. Assay results correlated well with those from radioimmunoassay. The method is simple, convenient, highly sensitive and can be used for routine clinical renin assays.     

Histopathological characteristics of rheumatoid arthritis--as a clue to elucidate its pathogenesis]

A correct histopathological diagnosis of Rheumatoid Arthritis (RA) is quite important for the decision of early phase treatment to cure it fundamentally. But, generally speaking, usual hospital pathologist is not so much experienced about RA. The purpose of this article is originally to let such pathologist familiar in RA pathology, but for the RA specialist to offer any clue to elucidate the still-unknown etio-pathogenesis of RA or to cure RA fundamentally. The "Tetralogy of RA Arthritis for pathologist" must be as follows: (1) Enormous proliferation of well-permeable granulation-tissue-type neo-vascularization, some of which became high column-endothelial and the center of primary as well as secondary follicle-like lymphoid cell cluster. (2) Lymphoid cluster in RA synovium is also pathological in function. It consisted of preferentially CD4T and B cells to produce IgG rheumatoid factor endlessly. (3) Synovial lining A and B cells proliferate as far as five layers of each, but later, the sublining D (M) and D (F) cells proliferate more and more and finally replace the lining cells. D (M) cells express macrophage marker and full of lysosome, on the contrary, D (F) cells express mesenchymal marker and contains much metalloproteinase. Both express strong Class II antigens but neither has complement activation inhibitor DAF. (4) Proliferation of these D cells with full of mesenchymal tissue destroying and inflammation accelerating activity must be playing a major role in the joint destruction of RA, some in shape of pannus and more in shape of granulation tissue in and around the bone.     

Contribution of a thickened cell wall and its glutamine nonamidated component to the vancomycin resistance expressed by Staphylococcus aureus Mu50

Staphylococcus aureus Mu50, which has reduced susceptibility to vancomycin, has a remarkably thickened cell wall with an increased proportion of glutamine nonamidated muropeptides. In addition, Mu50 had enhanced glutamine synthetase and L-glutamine D-fructose-6-phosphate aminotransferase activities, which are involved in the cell-wall peptidoglycan synthesis pathway. Furthermore, significantly increased levels of incorporation of (14)C-labeled D-glucose into the cell wall was observed in Mu50. Unlike a femC mutant S. aureus strain, increased levels of production of nonamidated muropeptides in Mu50 was not caused by lower levels of glutamine synthetase activity but was considered to be due to the glutamine depletion caused by increased glucose utilization by the cell to biosynthesize increased amounts of peptidoglycan. After the cells were allowed to synthesize cell wall in the absence or presence of glucose and glutamine, cells with different cell-wall thicknesses and with cell walls with different levels of cross-linking were prepared, and susceptibility testing of these cells demonstrated a strong correlation between the cell-wall thickness and the degree of vancomycin resistance. Affinity trapping of vancomycin molecules by the cell wall and clogging of the outer layers of peptidoglycan by bound vancomycin molecules were considered to be the mechanism of vancomycin resistance of Mu50. The reduced cross-linking and the increased affinity of binding to vancomycin of the Mu50 cell wall presumably caused by the increased proportion of nonamidated muropeptides may also contribute to the resistance to some extent.     

Novel Pseudomonas aeruginosa gene that suppresses tolerance to carbapenems

A biapenem-tolerant mutant of Pseudomonas aeruginosa was isolated by Tn1737KH insertion. The survival of the mutant 3 h after the addition of biapenem was about 1000 times greater than that of the wild type. The mutant was also tolerant to other biapenems, such as imipenem, panipenem, and meropenem.     

MR imaging of cervical carcinoma: comparison among T2-weighted,dynamic, and postcontrast T1-weighted images with histopathological correlation

Background: To identify the reasons for misdiagnosis of the degree of stromal invasion by uterine cervical cancer with various magnetic resonance sequences. Methods: T2-weighted, dynamic, and postcontrast T1-weighted images were obtained in the sagittal plane in 20 patients with uterine cervical cancer. After evaluating these sequences for the degree of stromal invasion, histologic specimens were directly correlated with these images. Results: The degree of stromal invasion was correctly diagnosed in 15 of the 20 cases on T2-weighted images, in 12 on dynamic images, and in eight on postcontrast T1-weighted images. All misdiagnoses were due to overestimation. Histologically, peritumoral stroma showed inflammation or edema in two patients, whereas no histological abnormality was found in the other patients. A hyperintense rim, i.e., a peritumoral enhanced ring-shaped structure, was observed on the enhanced images of five patients. The hyperintense rim corresponded to the periphery of the tumor in three patients and to the cervical stroma in two patients. Conclusion: T2-weighted images permitted the most accurate evaluation of stromal invasion by uterine tumors. Overdiagnosis may be due to an abnormal intensity of the cervical stroma, which was observed more frequently on dynamic and postcontrast T1-weighted images than on T2-weighted images. Received: 10 November 1995/Accepted after revision: 13 March 1996