Measurement of left atrial systolic time intervals in hypertensive patients using Doppler echocardiography: relation to fourth heart sound and left ventricular wall thickness.

The concept of left atrial systolic time intervals and Doppler echocardiography were used in a quantitative assessment of left atrial function in relation to the presence or absence of a fourth heart sound and to left ventricular hypertrophy in 47 patients with hypertension. Left atrial systolic time interval indexes included atrial pre-ejection period (the time between the onset of an electrocardiographic P wave and the onset of left ventricular inflow during atrial systole [A wave]), corrected atrial pre-ejection period (the atrial pre-ejection period divided by the duration of the P wave), and atrial ejection time (the time between the onset and cessation of the A wave). Twenty-one patients with a fourth heart sound on the phonocardiogram had a shorter atrial pre-ejection period (81 +/- 10 versus 89 +/- 14 ms p less than 0.05) and a corrected atrial pre-ejection period (66 +/- 17 versus 83 +/- 18 ms, p less than 0.01), as well as a longer atrial ejection time (147 +/- 15 versus 126 +/- 13 ms, p less than 0.001) than did 26 patients without a fourth heart sound. The ratio of atrial pre-ejection period to atrial ejection time and that of corrected atrial pre-ejection period to atrial ejection time was smaller in patients with than in patients without a fourth heart sound (0.56 +/- 0.08 versus 0.71 +/- 0.11, p less than 0.001; 0.46 +/- 0.16 ms-1 versus 0.67 +/- 0.17 ms-1, p less than 0.001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular structural characteristics in unilateral renovascular hypertension and primary aldosteronism.

To assess the importance of the renin-angiotensin system and plasma volume as determinants of hypertensive left ventricular hypertrophy and its anatomy, patients with unilateral renovascular hypertension and primary aldosteronism were studied by echocardiography. Blood pressure, age and sex were matched as closely as possible. The 19 patients with unilateral renovascular hypertension and the 19 patients with primary aldosteronism were similar in age, sex and blood pressure (168 +/- 19/97 +/- 11 and 163 +/- 17/99 +/- 10 mm Hg, respectively), but plasma volume was increased in the patients with primary aldosteronism. Interventricular septal thickness, left ventricular posterior wall thickness, left ventricular mass index and relative wall thickness did not differ between the 2 groups of patients. There was a significant correlation between the level of systolic blood pressure and either left ventricular mass index (r = 0.34, p less than 0.05) or relative wall thickness (r = 0.58, p less than 0.001) in both groups of patients. Left ventricular end-diastolic dimension index was increased in the patients with primary aldosteronism compared with those with unilateral renovascular hypertension (3.2 +/- 0.4 vs 2.9 +/- 0.3 cm/m2, p less than 0.02). When confined to the patients with systolic pressure greater than or equal to 150 mm Hg, relative wall thickness was significantly increased in the patients with unilateral renovascular hypertension. Patients with primary aldosteronism and unilateral renovascular hypertension of similar blood pressure levels, age and sex have almost identical degrees of left ventricular hypertrophy and anatomy. In contrast, the patients with primary oldosteronism had increased left ventricular dimension index.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochemical evidence for localization of AMPA-type glutamate receptor subunits in the dendritic raft.

A low density Triton-insoluble fraction with characteristic lipid composition was prepared from synaptic plasma membrane from the rat forebrain. The fraction was named dendritic raft based on its absence of the presynaptic marker synaptophysin, the presence of postsynaptic Glutamate receptor (GluR) subunits, and its resemblance to raft, caveolae-like structure. We found a differential distribution of NMDA-type and AMPA-type GluR subunits in the dendritic raft and postsynaptic density (PSD) fractions; the latter type GluR subunits were localized to the dendritic raft as well as PSD fraction, whereas the former type was mostly localized to the PSD fraction. We also found the differential distribution of the components of ras/mitogen-activated protein kinase (MAPK) pathway to the dendritic raft and PSD fractions. Dendritic raft and PSD may possibly interact at the postsynaptic sites for efficient signal processing that is required for expression of synaptic plasticity.

Heterogeneity of bovine corneal proteokeratan sulfate.

Proteokeratan sulfate was extracted and purified from bovine corneal stroma and then characterized by chemical and biochemical analyses. It was fractionated into several fractions by affinity chromatography on a concanavalin A-Sepharose column or by hydrophobic chromatography on a phenyl-Sepharose column. These fractions differed widely from one another in carbohydrate content, though no significant differences of their amino acid compositions were observed. One fraction (ca. 25%, on a dry weight basis) tightly bound to a concanavalin A-Sepharose column, compared with another fraction (ca. 65%) weakly bound to the same column, was poor in galactose and N-acetylglucosamine, but contained mannose in a high proportion. Fractions (ca. 30%) tightly bound to a phenyl-Sepharose column, in contrast to the one (ca. 66%) weakly bound, had low carbohydrate contents, like the fraction tightly bound to a concanavalin A-Sepharose column. Additionally, the fractions tightly bound to these affinity columns exhibited strong inhibitory actions on erythrocyte-concanavalin A agglutination. To obtain further details of the carbohydrate moiety of the proteokeratan sulfate, an attempt was made to separate and characterize peptidokeratan sulfate and Asn-linked oligosaccharide derived from some proteokeratan sulfate fractions. The present work revealed that the proteokeratan sulfate contains keratan sulfate and high mannose-type oligosaccharide in an approximate chain number ratio of 3.5:1.0, the keratan sulfate content varies widely and the oligosaccharide content increases with decrease of the keratan sulfate content, and the protein core is homogeneous at least with respect to the amino acid composition.

Improved purification of Aspergillus oryzae 1,2-alpha-mannosidase by using mannan gel affinity chromatography.

In order to facilitate the purification of 1,2-alpha-mannosidase from an enzyme product of Aspergillus oryzae, we have devised a rapid and simple procedure. A partially purified enzyme preparation obtained from the A. oryzae enzyme product, by means of ammonium sulfate fractionation followed by CM-Sephadex C-50 chromatography, was subjected to affinity chromatography with baker's yeast mannan gel as an adsorbent. 1,2-alpha-Mannosidase was retarded and well separated from the major protein peak on the affinity column. After a second affinity chromatography under the same conditions, 1,2-alpha-mannosidase was finally purified 7,500-fold with a 22.9% yield. The enzyme preparation thus obtained was quite suitable for the structural analysis of glycoconjugates.

Purification and characterization of endo-beta-N-acetylglucosaminidase of Aspergillus oryzae.

An endo-beta-N-acetylglucosaminidase which hydrolyzes the N,N'-diacetylchitobiosyl linkage in asparagine-linked oligosaccharides was purified from the enzyme product of Aspergillus oryzae. Its substrate specificity was similar to that of endo-beta-N-acetylglucosaminidase H from Streptomyces griseus with respect to the relative activities toward the glycopeptides obtained from ovalbumin and bovine IgG. The present endoglycosidase exhibited a broad optimum pH range and was relatively stable. Metal ions, chelating agents and D-mannose did not have a significant effect on the enzyme activity.

Inhibitory effect of M50054, a novel inhibitor of apoptosis, on anti-Fas-antibody-induced hepatitis and chemotherapy-induced alopecia.

M50054, 2,2'-methylenebis (1,3-cyclohexanedione), was identified as a novel inhibitor of apoptosis (programmed cell death) using an in vitro cell death assay system induced in human Fas-expressing WC8 cells by soluble human Fas ligand. Furthermore, M50054 inhibited the apoptotic cell death of U937, a human monocytic leukemic cell line, induced by anticancer agents such as etoposide; it was also confirmed that M50054 inhibited apoptotic features such as DNA fragmentation and phosphatidylserine exposure in these cells. These anti-apoptotic effects were attributable to inhibition of caspase-3 activation. Additionally, M50054 significantly inhibited anti-Fas-antibody-induced elevation of plasma alanine aminotransferase and aspartate aminotransferase. Alopecia (hair loss) symptoms were also significantly improved with topical treatment with M50054. In conclusion, M50054 inhibits apoptosis induced by a variety of stimuli via inhibition of caspase-3 activation, and may thus be effective for hepatitis and chemotherapy-induced alopecia.

Induction by 5-aza-2'-deoxycytidine, an inhibitor of DNA methylation, of Le(y) antigen, apoptosis and differentiation in human lung cancer cells.

We recently developed a monoclonal antibody directed to carbohydrate antigen Le(y), BM-1/JIMRO, and found that expression of Le(y) antigen defined by BM-1/JIMRO was associated with the process of apoptosis, but not with cell proliferation or necrosis. In the present experiments, we examined with BM-1/JIMRO the effects of various differentiation inducers on the growth and expression of Le(y) antigen in human lung cancer A549 cells. We found that a specific inhibitor of methylation of DNA, 5-aza-2' deoxycytidine (ADC), could markedly induce expression of Le(y) antigen in association with induction of apoptosis and differentiation in the A549 cells. These results suggest that hypomethylation of DNA is involved in the molecular mechanisms of induction of Le(y) antigen, apoptosis and differentiation in the cells.

Induction of Ley antigen by 5-aza-2'-deoxycytidine in association with differentiation and apoptosis in human pancreatic cancer cells.

We investigated the effect of 5-aza-2'-deoxycytidine (ADC) (a specific inhibitor of DNA methylation) on differentiation, Lewisy (Ley) antigen expression, and DNA fragmentation (a biochemical marker of apoptosis) in human pancreatic cancer MIA PaCa-2 cells. ADC markedly inhibited the growth of MIA PaCa-2 cells. Flow cytometric analysis showed that ADC suppressed the cell population in the G1 phase, but enhanced it in the G2/M phase. On the other hand, several markers of cell differentiation including morphological and biochemical alterations were distinctly induced in cells treated with ADC. Morphologically, the cells were enlarged and thinner than the untreated control cells, and intracellular alkaline phosphatase (ALP) activity was markedly increased. Additionally, biochemical markers of apoptosis including DNA fragmentation and Ley antigen expression were induced in association with the appearance of morphological and biochemical markers of differentiation (ALP). These results suggest that the hypomethylation of DNA is involved in the molecular mechanism of growth inhibition, induction of apoptosis, and differentiation in human pancreatic cancer MIA PaCa-2 cells.

Pulse intravenous cyclophosphamide treatment for steroid-resistant interstitial pneumonitis associated with polymyositis.

Interstitial pneumonitis (IP) is a serious complication in polymyositis/dermatomyositis (PM/DM), leading to significant morbidity or mortality. Here, we report the successful treatment by pulse intravenous administration of cyclophosphamide in the early course of lung involvement in PM, and with subsequent low-dosage oral administration of azathioprine in a patient with steroid-resistant IP associated with PM/DM. Although the precise pharmacological mechanism induced by cyclophosphamide in this disease remains unclear, such a cytotoxic drug raises the possibility of control of steroid-resistant PM/DM-associated IP when used in the early course of IP.

Assessment of coronary artery bypass surgery by exercise thallium imaging.

The purpose of this study was to assess the coronary artery bypass grafting (CABG) in exercise thallium-201 scintigraphy. The study was performed on 18 consecutive patients undergoing elective surgery. We compared the results of the scintigraphic examinations, 1 week before and 1 month postoperatively. Of the 47 bypass grafts, 20 (42. 6%) grafts contributed to the improvement of the ischemic areas and 38% of the bypass grafts did not change the scintigraphic patterns after surgery. Some bypass grafts had been performed on the stenotic arteries that dominated the areas which preoperatively showed normal exercise scintigraphic patterns yet were considered to worsen in the near future. Such grafts main contribution may be to protect and to increase the overall myocardial washout ratio for prevention of an enlargement of ischemic areas.

[Human respiratory tract infection by Pasteurella multocida subsp. multocida presumably derived from the cat].

Pasteurella multocida is a Gram-negative short rod-shaped bacteria that has been recognized as a pathogen of hemorrhagic septicemia and fowl cholera in the veterinary medicine. Infections by this microorganism as seen in the foreign literature vary widely from local infections due to bites and scratches by animals to general infections such as infections of the respiratory tract, sepsis, and meningitis. In Japan, reported cases of P. multocida infections are predominantly local infections, followed by respiratory infection. Recently, death of diabetic patients due to septicemia by this pathogen has also been reported. In this study, we experienced a case of respiratory tract infection in which the pathogen P. multocida subsp. multocida was suggested to have been transmitted from a pet cat by the agreement of the serotype of the bacterial isolates between the patient and the cat. This case was evaluated from the zoonotic viewpoint. The patient was a 68-year-old male who had been followed up since 1982 with a diagnosis of bronchiectasis. After his referral to our hospital, P. multocida subsp. multocida was isolated from his bloody sputum and, then, from the cat kept by the patient. The tow isolates were identical in terms of the biochemical properties, drug susceptibility profile, and serotype (-:1), and the derivation of P. multocida subsp. multocida infection from cat was established for the first time in this report. The incidence of P. multocida infections is increasing in Japan, and particular attention is considered to be needed about these conditions as zoonoses as indicated in "Preventive Measures against Zoonoses Derived from Pet Animals (Dog, Cat)", an official communication from the Ministry of Health and Welfare to related institutions in 1989. Also, to check whether the patient keeps any pet at the clinical inquiry is a practice of bacteriological importance in all fields of medicine.

A 22-year course of the Kay-Shiley disc valve with muscle guard at the mitral position.

Almost 33 years have elapsed since the introduction of the Kay-Shiley disc valve in Japan. Following the development of pyrolite carbon, the Kay-Shiley valve is no longer in clinical use. We report the case of a female patient who had had an isolated mitral valve replacement with the Kay-Shiley disc valve with single muscle guard 22 years previously. After numerous thromboembolic episodes with the Kay-Shiley disc valve, a successful reoperation was done with the CarboMedics valve. The explanted valve revealed that the grooved occluder disc had a loosely adherent clot. The thromboembolism is a notorious complication associated with this valve. We recommend re-replacement of the Kay-Shiley valve whenever possible.

[Necessity and usefulness of detection by PCR of mecA and aac(6')/aph(2") genes for identification of arbekacin-resistant MRSA].

Arbekacin (ABK)-resistant bacteria (43 strains) isolated as MRSA by regular clinical procedures in Japanese clinics in 1998 were characterized in terms of taxonomic properties, aminoglycoside resistance, and mecA and aac(6')/aph(2") genes linking with ABK-resistant MRSA. Taxonomically the 43 strains fell into Staphylococcus aureus (33 strains) and Enterococcus (10 strains). As to ABK resistance, the 13 strains of MRSA clinically reported as high ABK resistance (128 micrograms/ml or higher) did not show clear high ABK resistance except for 2 strains when their ABK resistance was tested using 0.5% NaCl containing nutrient agar. We designed and established the primers and conditions for PCR to detect the above two resistance genes. PCR analysis of DNAs from the 43 strains clearly indicated that only 33 strains identified taxonomically as S. aureus possessed mecA indicating MRSA and 23 out of them possessed aac(6')/aph(2"). The other 10 strains of MRSA lacking aac(6')/aph(2") were ABK-sensitive. Thus, there were a good correlation between ABK resistance and aac(6')/aph(2") existence. Based on these, it was conclusive that the appropriate ABK resistance test as well as the detection of mecA and aac(6')/aph(2") genes by PCR are necessary and useful to avoid false ABK-resistant MRSA strains.

[Clinical efficacy of cefotaxime in the field of internal medicine].

Fifty-eight patients were treated with cefotaxime (CTX, Claforan) intravenously. Almost all patients (54 patients) had underlying diseases that were 16 cases of diabetes mellitus, 10 cases of respiratory diseases, 8 cases of cerebral vascular disturbance, 6 cases of renal diseases and blood diseases, 5 cases of carcinoma and hypertension, 4 cases of cholelithiasis, 3 cases of heart diseases and 7 cases of other diseases. The clinical efficacy of CTX in 34 cases of RTI, 11 cases of UTI, 8 cases of BTI and 5 cases of other infection was excellent in 11 cases, good in 27 cases, fair in 12 cases, poor in 4 cases and unclear in 4 cases. The over all clinical effectiveness was 70.4%. No adverse reaction was observed except for 2 cases (general fatigue in 1 case and eruption and itching in another). These results obtained should support the usefulness of CTX.

[Prophylactic intravesical BCG for bladder tumor after surgery of upper tract urothelial carcinoma].

We report the result of prophylactic intravesical instillation of BCG after surgery of upper tract urothelial carcinoma. The BCG Tokyo 172 strain was given preoperatively and/or postoperatively, as a rule, in a dose of 80 mg in 30 ml saline instilled into the bladder. Only one (14.3%) of the 7 patients with intravesical BCG developed bladder tumor at 14 month after surgery, while (45.4%) of 11 patients who did not receive intravesical BCG suffered from bladder tumor within 2 years after surgery. Prophylactic intravesical instillation of BCG reduced significantly (p less than 0.005) the recurrence of bladder tumor after the surgery of renal pelvis and ureteral tumor.

[Extraction of infected pacemaker electrode using catheter and snare].

A 85-year-old man had undergone implantation of a transvenous pacemaker system in 1982. Nine years later the generator was explanted and he was underwent implantation of a new generator and electrode. After one year of the second operation, infection of the old electrode had been noted and it was not cured in spite of partial explantation of the infected electrode and appropriate antibiotic therapy. We decided to remove the infected electrode and succeeded in extraction using catheter and snare. The patient's recovery was uneventful. We suggest catheter and snare is useful for explantation of chronic transvenous pacemaker electrodes.

[Successful treatment by Konno's operation for congenital aortic stenosis associated with hypoplastic valve ring].

A 47-year-old woman with congenital aortic stenosis associated with hypoplastic aortic valve ring underwent aortic valve replacement by Konno method. We have to be careful preventing residual VSD because the left ventricular muscle was weak in the aged with congenital aortic stenosis. In early postoperative period, we also have to do a careful treatment in case by Konno's operation, particularly in the patient of advanced age. However, she made a satisfactory recovery with adequate size of aortic valve replacement.

[Long-term results of percutaneous transluminal angioplasty in patients with renovascular hypertension--a follow-up study on renal function and renal size].

Twenty patients with renovascular hypertension were followed for at least 1 year (mean 3.3 years) after successful percutaneous transluminal angioplasty (PTA). Renal arteries were patent in 13 (65%) patients and were re-stenosed in 7 (35%). In 12 patients with unilaterally stenosed renal artery which were patent at the end of the follow up period, 6 patients were normotensive, the other 6 patients had less degree of hypertension. Determinations of renal vein renin were only of limited prognostic value. Renal blood flow pattern by doppler echography improved after PTA in the 12 patients. Radioisotope renogram showed tendency of improved Tmax ratio (stenotic kidney/nonstenotic kidney) from 1.5 +/- 0.8 to 1.0 +/- 0.2 (mean +/- SD, p less than 0.1). Serum creatinine levels decreased significantly from 1.2 +/- 0.5 mg/dl to 1.0 +/- 0.2 mg/dl (p less than 0.05) and creatinine clearance increased from 72.1 +/- 18.5 ml/min to 99.6 +/- 31.7 ml/min (p less than 0.02). The size of the stenosed kidneys increased from 11.2 +/- 0.7 cm to 12.0 +/- 0.8 cm (p less than 0.01), while the size of the contralateral kidneys did not change. These results indicate that PTA has favorable long-term effects on blood pressure and renal function with restoration of renal size in cases with patent renal arteries after this procedure.

[A case of gastric cancer with multiple liver metastases effectively treated with PMUE (CDDP, MMC, UFT, etoposide) hepatic arterial chemotherapy].

A 62-year-old male patient with progressive gastric cancer and multiple liver metastases (H3, P0, ss gamma, n4) underwent total gastrectomy (R1). After 2 years and 2 months, he was re-hospitalized with epigastric tumor caused by re-manifestation of liver metastasis as well as inappetence. Since a large focus of liver metastasis and intraportal tumor embolism was identified, a continuous intraarterial infusion tube utilizing Infuse-A-Port was inserted in the hepatic artery. After conducting 2 cycles of PMUE intra-arterial chemotherapy, the tumor size was reduced by 84% (PR); and CEA, which had been high upon rehospitalization, recovered to the normal level. After discharge, the patient has been receiving 5-FU arterial infusion as an outpatient and undergoing UFT oral chemotherapy. The efficacy has continued and he has been well for 3 years since operation. Often operations for gastric cancer accompanied with multiple liver metastasis meet with little success, and almost no case of prolonged survival has been reported. In this case, the effectiveness of PMUE arterial infusion chemotherapy was clear, the patient has been well for 3 years since operation, and is an interesting example with seemingly good prospects for long-survival.