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To better understand the spread of hepatitis C virus (HCV) infection, we studied the association of HCV infection with similarly transmissible hepatitis B virus (HBV) infection and with hepatitis A virus (HAV) infection, which is supposed to be related to a nosocomial transmission of HCV. This was done by studying the presence or absence of antibodies to these viruses, as well as hepatitis B surface antigen, in a population of 1,398 inhabitants with abnormal liver function tests or history of liver disease and/or blood transfusion. This group was drawn from a group of 7,905 examinees screened for liver disease in 26 districts of Okayama prefecture, Japan. The prevalence of antibody-positive cases increased with age for those viruses. Small but significantly increased odds ratios were obtained among anti-HCV antibodies (HCVAb), anti-hepatitis B core antibodies (HBcAb) and anti-hepatitis A antibodies (HAVAb). After adjusting odds ratios by logistic regression analysis, a significant association was present only between HCVAb and HBcAb. The distribution of age-adjusted prevalences (AAP) of HCVAb in 26 districts was significantly wider than those of HBcAb or HAVAb. The district-based AAP of HCVAb, but not of HBcAb and HAVAb, correlated significantly with the district-based prevalence of infectious hepatitis having a tendency of chronicity reported in 1953-1955. Adjusted odds ratios calculated by logistic regression analysis of the virus markers showed that HCVAb was significantly associated with a past history of blood transfusion. Thus, the spread of HCV infection is speculated to have been triggered by blood transfusion, particularly from paid donors initially, followed by transmission by nosocomial or close person-to-person contact.

Our purpose was to investigate developmental alterations of human alpha-fetoprotein (AFP) oligosaccharides in maternal serum by lectin affinity electrophoresis and to compare the AFP glycoforms in maternal serum with those in umbilical cord serum and amniotic fluid. AFP glycoforms were separated by affinity electrophoresis with concanavalin A (Con A), lentil lectin (LCA), erythroagglutinating phytohemagglutinin (E-PHA) and Allomyrina dichotoma lectin (allo A) and detected by sensitive antibody affinity blotting. In maternal serum, increased proportions of Con A-nonreactive AFP (AFP-C1), LCA strongly-reactive AFP (AFP-L3) and E-PHA-reactive AFP (AFP-P4 and AFP-P5) decreased gradually during the early gestational weeks. Allo A-nonreactive AFP (AFP-A1 and asialo-AFP) were found only in amniotic fluids during early gestational weeks. The percentages of these glycoforms at full term were almost the same among those body fluids. Since the glycoforms of maternal serum AFP were close to those of umbilical cord serum AFP, lectin-affinity electrophoretic analysis of maternal serum AFP may be useful for evaluating the developmental state of fetus by examining the nature of AFP sugar chain.

A double-masked, randomized, placebo-controlled study was conducted to evaluate the effectiveness of lodoxamide tromethamine 0.1% eyedrops in preventing inflammatory cell accumulation in the tear fluid of patients with vernal conjunctivitis. A 1-week baseline period was followed by 4 weeks of treatment with either lodoxamide tromethamine 0.1% ophthalmic solution or placebo in 30 symptomatic subjects with vernal conjunctivitis. Cytological evaluation of tear fluid was performed before and after the treatment. In the lodoxamide-treated group, but not in the placebo-treated group, the number of neutrophils (P = 0.051) and eosinophils (P = 0.020) in the tears significantly decreased at the end of 4 weeks when compared with baseline (Wilcoxon-signed rank test). It was concluded that lodoxamide treatment was significantly more effective than the placebo in terms of reducing inflammatory cells in the tear fluid in vernal conjunctivitis. This objective inhibition of inflammatory cells may be associated with clinical relief.

We developed a reliable system for the irradiation of xenografted tumors in mice which allows for accurate local irradiation under specific pathogen-free conditions. The system presented here consists of acrylic supports for mice and an acrylic box connected to a pump through 0.22 microns pore-sized filters. Mice with xenotransplanted tumors growing on their right hind legs were set on the supports and put into the box in a laminar flow hood. The tumors of 7 mice were irradiated simultaneously with X-rays of 6 and 10 MV generated by a linear accelerator at a dose rate of 3.1-4.7 Gy/min. The air was ventilated through filters during irradiation in the closed box. Microorganism tests confirmed that no bacteria entered or left the box. One of the significant characteristics of this setup is that it allows for irradiation under conditions of acute hypoxia, which is obtained using an integrated tourniquet. The dose variation among 7 tumors was less than 1%. The rest of the mouse's body was shielded effectively by a half-field technique and a lead block. As a result, the whole body dose for the mice was 0-4% of the total dose absorbed by the tumor. Due to the high dose rate and the ability to irradiate 7 mice simultaneously under specific pathogen-free conditions, this new system can be considered a time-saving and valuable tool for radiation oncology research.

The pharmacodynamic effects of cisdiamminedichloroplatinum(II) (CDDP) in vitro have been reported, but the dosage and exposure time in vitro have not been based on clinical observations of the drug's actions in vivo. In this study, the authors attempted to evaluate the pharmacodynamic effects of CDDP in vitro in terms of cell survival and DNA crosslinking by simulating unbound CDDP administration at varying concentrations to a rat mammary adenocarcinoma line (known as line 66). CDDP exposure was conducted by both constant concentration procedures and a simulated in vivo procedure. Colony formation assay for the surviving fraction and alkaline elution assay for DNA crosslink measurement were performed in order to evaluate the pharmacodynamics of CDDP. Cell survival was a function of the area under the drug concentration time curve (AUC) of unbound CDDP (R2 = 0.77, P < 0.002) for all drug exposure procedures as analyzed by the analysis of covariance test. There was a strong correlation between the surviving fraction and the crosslink index of the total amount of DNA crosslinks (R2 = 0.85, P < 0.0005). Both the total amount of DNA-DNA crosslinks and the DNA-protein crosslinks, of which the latter were dominant, were affected not by the exposure procedures, but by the AUC value (P < 0.002). The thresholds of cytocidal effect were 1.59 mg.h/l for the AUC and 0.008 for the crosslink index. The pharmacodynamic effects in vitro by simulated in vivo exposure were identical to those of constant.

The effects of thimerosal, a sulfhydryl oxidizing agent on nitrergic, endothelium-dependent and -independent relaxations were investigated to examine the possibility that the nitrergic neurotransmitter and endothelium-derived relaxing factor (EDRF) could be S-nitrosothiol or free nitric oxide (NO) in the isolated mouse corpus cavernosum. Thimerosal (5 x 10(-6)-2 x 10(-5) M) inhibited or almost abolished electrical field stimulation--(EFS, 30V, 0.5 ms, 15 sec, 1, 2, 4, 8, 16 Hz), acetylcholine--(ACh, 5 x 10(-8)-1.25 x 10(-6) M), glyceryl trinitrate--(GTN, 3 x 10(-7)-3 x 10(-6) M), and S-nitrosoglutathione--(GSNO, 5 x 10(-6)-1.25 x 10(-4) M) induced relaxations. Thiomerosal inhibition seems to be specific to L-arginine NO pathways since it had no effect on acidified sodium nitrite--(10(-4)-5 x 10(-4) M), photoactivated sodium nitrite--(2 x 10(-4) M), isoprenaline--(10(-6) M), or papaverine--(10(-4) M) elicited relaxations. Moreover, the inhibitory effect of thimerosal on the nitrergic, ACh- or GTN-induced relaxations were partly reversed by sulfhydryl-containing compounds, L-cysteine (10(-3) M), dithiothreitol (10(-3) M), or glutathione (10(-3) M). However L-methionine (10(-3) M), which contains a methyl group on the sulphur atom, failed to restore the thimerosal inhibition. Thimerosal did not change the contraction produced by 10(-4) M NG-nitro-L-arginine methyl ester. These findings indicate that the nitrergic neurotransmitter as well as EDRF may not be free NO but NO-transferring molecules, probably S-nitrosothiols, in the mouse corpus cavernosum.

The relationship between endogenous cytokine antagonists and surgical stress is poorly understood. Surgical stress induces immunosuppression, and the reversed therapy of postoperative immunosuppression has been expected. The aim of the present study was to assess the effect of a serine protease inhibitor on postoperative immune reactivity. Twenty patients with colorectal cancer were randomly separated into experimental and control groups of 10 patients each. The experimental group received perioperative administration of a serine protease inhibitor while the control group did not. Plasma levels of cytokine antagonists, which suppress cell-mediated immunity, such as cortisol, interleukin-1 receptor antagonist, soluble interleukin-2 receptor (sIL-2R) and soluble tumor necrosis factors p55, p75 (sTNF-R55, -R75) were simultaneously measured. Significant reductions of plasma concentration of sIL-2R and sTNF-R55 were observed. Perioperative administration of a serine protease inhibitor may contribute to ameliorating immunosuppression after major surgery.

A unilateral variation in the origin and distribution of the arterial pattern of the human upper extremity on the right side is reported on. Apart from its usual branches, the third part of the right axillary artery gave origin to a common branch, the profunda brachii artery and the superior ulnar collateral artery. The right brachial artery, at a point 5.0 cm distal to its origin, bifurcated into the radial and ulnar arteries; their origin was in a position opposite the usual location. The radial artery continued on the medial side of the arm for 2.5 cm and crossed the ulnar artery anteriorly to gain a lateral position in the arm. The inferior ulnar collateral artery arose not from the brachial artery, but from the ulnar artery. A muscle variation was also observed in the right hand, which is compatible with the notion variations within one system of a limb will frequently be accompanied by variations in other systems of the same limb.

Genomic sequencing and chromosomal assignment of the gene encoding rat APEX nuclease, a multifunctional DNA repair enzyme, were performed. An active Apex gene and a processed pseudogene were isolated from a rat genomic library. The active Apex gene consists of 5 exons and 4 introns spanning 2.1 kb. The putative promoter region of the Apex gene lacks the typical TATA box, but contains CAAT boxes and a CpG island having putative binding sites for several transcription factors, such as Sp1, AP-2, GATA-1 and ATF. A putative O-sialoglycoprotease (a homologue of Pasteurella haemolytica glycoprotease, gcp; abbreviated as Prsmg1/Gcpl1) gene consisting of 11 exons and 10 introns spanning 7.3 kb lies immediately adjacent to the Apex gene in a 5'-to-5' orientation. The Apex gene locus was mapped to rat chromosome 15p12 using in situ hybridization. The processed pseudogene (designated as rat Apexp1) has a nucleotide sequence 87.1% identical to that of the rat Apex cDNA, although several stop codons interrupting the coding sequences and multiple nucleotide deletions were observed. The Apexp1 is located in an inactive LINE sequence. Calculation of nucleotide substitution rates suggests that the immediate, active progenitor of Apexp1 arose 23 million years ago and that the non-functionalization occurred 15 million years ago.

The influence of mild exercise on skeletal muscle fibers was investigated histochemically to assess the effects of exercise on steroid myopathy and its efficacy for preventing this disease. Twenty male Wistar rats were divided into 4 groups of 5 each: group T, which received exercise alone; group S which received steroid alone; group ST which received both exercise and steroid; and group C, the control group. In groups S and ST, hydrocortisone was administered subcutaneously at a dose of 10 mg/kg/day for 4 weeks. In the exercise groups, the animals were made to run at a speed of 15 m/min for about 1 h/day for 5 days a week on a treadmill. After the completion of treadmill exercise and steroid administration for 4 weeks, the rats were anesthetized with Nembutal, the soleus muscle (SOL) and the extensor digitorum longus muscle (EDL) were removed and prepared for examinations. The area of type I fibers in the SOL was significantly larger in group ST than in group S. The area of type IIa fibers in the EDL was significantly larger in group ST than in group S. In group S, the proportion of type I fibers in the SOL was significantly lower than in the other three groups. There was little difference in fiber type distribution between groups ST and C. These results suggest that steroid myopathy can be prevented by even mild exercise.

To evaluate the efficacy and safety of additive triple disease modifying anti-rheumatic drug (DMARD) combination therapy of a low dose of sulfhydryl compounds inverted question markD-penicillamine, bucillamine or tiopronin inverted question mark, sulfasalazine (SSZ) and methotrexate (MTX) as a treatment for rheumatoid arthritis (RA) patients, we studied a total of 33 Japanese RA patients (6 males, 27 females). At 1 or 2 months after simultaneous administration of the 3 above-mentioned DMARDs was begun, significant improvements were seen in markers of joint inflammation, i.e., erythrocyte sedimentation rate and C-reactive protein in sera. At 6 months, clinical improvement judged by the physicians' overall assessment of joint symptoms and laboratory data was observed in 29 (88%) of the 33 RA patients. No marked effect was observed in the other 4 (12%) patients, however. We observed no significant adverse reaction to this therapy. This suggests that additive triple DMARD combination therapy of a low dose of sulfhydryl compounds, SSZ and MTX could be a useful drug therapy for the treatment of RA patients, even those who are refractory.

Life expectancy, mortality and longevity data related to height and body size for various US and world population samples are reviewed. Research on energy restriction, smaller body size and longevity is also examined. Information sources include various medical and scientific journals, books and personal communications with researchers. Additional information is presented based on research involving eight populations of the world noted for their health, vigor and longevity. This information includes the findings of one of the authors who led research teams to study these populations. While conflicting findings exist on the cardiovascular death rates for shorter people, many examples of short populations with very little heart disease are described. Most cancer studies indicate that shorter people have significantly lower mortality risk. Considerable data suggest that shorter people generally have greater longevity than taller people, and extensive animal research supports human longevity findings. Tall populations with low mortality rates are also described. Shorter stature and smaller body weight appear to promote better health and longevity in the absence of malnutrition and infectious diseases. Several theoretical reasons for this greater longevity potential are covered. Also discussed, is the role of socioeconomic status, diet, relative weight, environment and other factors in increasing or decreasing the longevity of individuals, regardless of their heights and weights.

Nipradilol (3,4-dihydro-8-(2-hydroxy-3-isopropylamino) propoxy-3-nitroxy-2H-1-benzopyran) is a newly synthesized chemical agent designed to possess beta-adrenoceptor blocking and vasodilating actions. Nipradilol decreased left ventricular contractility index (Emax, slope of the ventricular end-systolic pressure-volume relation), systolic pressure-volume area (PVA, a measure of ventricular total mechanical energy) and oxygen consumption in cross-circulated excised dog hearts. However, nipradilol did not decrease total coronary resistance. These results indicate that nipradilol, like propranolol, depresses myocardial mechanoenergetics and that the vasodilating action of nipradilol could not be detected in the present study.

Efficacy of the percutaneous transluminal coronary recannalization (PTCR) therapy was evaluated by weighting infarct-related coronary artery segments in 28 consecutive patients with acute myocardial infarction. The study focused on the influences of the time interval from the onset of chest pain to PTCR (PTCR-Time) and on the post-infarct left ventricular regional wall motion in conjunction with the serum levels of GOT, LDH and CPK and with PTCR-Time. PTCR success rate was 84.0%, and re-occlusion rate was 4.0%. The thrombolysis in myocardial infarction grade 2, however, was observed in 7 (33.3%) of 21 cases with successful PTCR. There was no significant difference in PTCR-Time between the PTCR success and nonsuccess groups. Significant correlations were observed between the PTCR-Time and each peak value of standardized serum levels of LDH and CPK, and between the PTCR-Time and the post-infarct regional wall motion abnormality. There were also significant correlations between the standardized serum level of each of these three enzymes and the post-infarct regional wall motion abnormality. It was clearly demonstrated that the earlier the recannalization of the infarcted artery was achieved, the less extensive the myocardial damage in quantitative and qualitative aspects.

A 44-year-old man with alcohol-induced chronic pancreatitis was referred to our institute for evaluation of severe anemia. The hemoglobin was 2.6g/dl. The results of upper gastrointestinal and colonic examination were negative. Computed tomography and ultrasound examination revealed a pseudocyst in the head of the pancreas. A pseudoaneurysm of the anterior superior pancreaticoduodenal artery shown by angiography appeared to have caused gastrointestinal bleeding by rupturing into the pancreatic cyst connected to the main pancreatic duct. A pyrorus-preserving pancreaticoduodenectomy was performed successfully.

The effects of centrally administered interleukin-1 beta (IL-1) or platelet activating factor (PAF) on adrenocorticotropin (ACTH) and catecholamine secretion, blood pressure and heart rate were examined to determine if these agents stimulate similarly the hypothalamic-pituitary-adrenal (HPA) axis or the sympathetic-adrenomedullary system. Intra-third ventricular administration of IL-1 (50, 200 ng) evoked significant ACTH secretion. Centrally administered IL-1 (50 ng) elevated plasma noradrenaline and adrenaline levels, systolic blood pressure and heart rate. Plasma ACTH, noradrenaline and adrenaline levels were also increased by the higher dose (200 ng) of IL-1 while systolic blood pressure and heart rate were not affected. Intra-third ventricular administration of 9 micrograms of PAF elevated the plasma ACTH level while 3 micrograms of PAF did not stimulate ACTH secretion. Neither dose of centrally administered PAF affected any plasma catecholamine level or systolic blood pressure. These results suggest that central IL-1 stimulates both the HPA axis and the sympathetic-adrenomedullary system, that a higher dose of IL-1 stimulates a mechanism to antagonize the elevation of blood pressure and heart rate and that central PAF is not involved in the control of the sympathetic-adrenomedullary system. Thus, IL-1 and PAF do not interact in the brain, although they interact peripherally.

Lymphokine activated killer (LAK) cells can destroy not only tumor cells but also syngeneic liver cells. In this study, the effects of passive transfer of LAK cells on liver regeneration were examined by the 3H-thymidine uptake and bromodeoxyuridine (BrdU) labeling methods after resection of 70% of the volume of the liver. LAK cells were infused 12h after hepatectomy and the effects on regeneration of liver cells were examined 36 h later. The transfusion of LAK cells induced significant inhibition of liver regeneration at a dose of 5-10 x 10(7) cells. Neuraminidase treatment of lymphocytes is desirable to enhance the selective entrapment of LAK cells into the liver. When LAK cells were treated with neuraminidase (0.5 units/ml), and transfused into hepatectomized mice, more potent suppression of liver regeneration was induced in comparison with the same dose of LAK cells. The intraperitoneal injection of recombinant interleukin 2 (rIL-2) after partial hepatectomy also inhibited the regeneration of remnant liver. From these results, lymphocytes such as LAK cells appear to regulate liver regeneration.

The distribution of lectin receptors in the human tonsil was studied using 16 biotinylated lectins. The avidin-biotin-peroxidase complex (ABC) method was used on frozen and paraffin-embedded tissue sections. Cell suspensions were also analysed by dual flow cytometry using respective fluorescein isothiocyanate-conjugated lectins and phycoerythrin-labeled anti-CD3 and anti-human immunoglobulin. Frozen sections fixed with acetone and paraffin-embedded materials fixed in three solutions were compared for lectin affinity; ethanol-fixed sections gave best results followed by frozen and buffered formalin-fixed ones, then nonbuffered formalin. Con-A, RCA-1, LcH, WGA, MPA, PHA, PSA, PNA, SJA and GSA-1 reacted with all tissue components of the tonsil in immunohistochemical studies, but binding intensity was fixative dependent. Binding of Lotus and BPA to lymphocytes was limited to germinal center lymphocytes. Other tissue components were also reactive but staining intensity was weaker in Lotus compared with BPA. SBA and DBA did not react with lymphocytes, but reacted with macrophages/histiocytes, vascular endothelia, and epithelial cells. LBA and LPA were constantly negative with all tissue components irrespective of fixatives. Flow cytometric analyses showed that all but three (DBA, LBA and LPA) partially or totally stained lymphocyte surfaces. Lotus receptors were expressed exclusively on B-lymphocytes.

Ten radiograph signs were assessed by two experts for their usefulness in the diagnosis of small solitary peripheral pulmonary nodules less than 3 cm. The ten categories included notching, spicula formation, pleural indentation, vascular convergence, contour, paleness, homogeneity, cavitation, air bronchogram, and calcification. The cases included 134 lung cancers and 44 benign lung lesions resected between 1972 and 1988 at the Second Department of Surgery, Okayama University Medical School. Notching, spicula formation, pleural indentation, vascular convergence, contour, and air bronchogram were useful signs in differentiating lung cancer from benign lung lesions. However, since the radiograph signs exhibited great variation in both lung cancer and benign lung lesions, a diagnostic operation is sometimes inevitable.