検索

To investigate whether an association exists between vascular endothelial growth factor (VEGF) expression and tumor prognosis in primary lung carcinoma, we used immunohistochemical techniques to analyze microvessel density and VEGF expression in lung carcinoma tissue from 98 patients. Tissue had been fresh-frozen at the time of operation and preserved for more than 5 years. The results indicated that VEGF expression was positive for 50 of the 98 patients (51.0%), with 27 (27.6%) being weakly positive and 23 (23.5%) being strongly positive. The microvessel density in tissue showing weakly positive and strongly positive VEGF expression was significantly higher than that in VEGF-negative tumor tissue (P < 0.05: negative vs. weakly positive, P < 0.01: negative vs. strongly positive), we showed demonstrating that VEGF expression was significantly associated with intratumoral microvessel density. The 5-year survival rates were 8.7% for strongly VEGF-positive patients, 43.9% for weakly VEGF-positive patients and 79.2% for VEGF-negative patients, respectively (P < 0.01: negative vs. weakly positive or strongly positive). Furthermore, multivariate analysis employing multiple regression analysis indicated that VEGF expression correlates highly with the overall survival rates of patients with primary lung carcinoma. Two variables, N status and VEGF expression, were found to be significant prognostic factors (P < 0.01). The results of this study suggest that VEGF expression is associated with intratumoral microvessel density. VEGF expression may constitute important independent prognostic evidence that can help us in predicting the outcomes of patients with primary lung carcinomas.

The present study showed that many neurons in the adult rat brain possessed a perineuronal sulfated proteoglycan surface coat which reacted to cationic iron colloid and aldehyde fuchsin. This surface coat was stained supravitally with Ehrlich's methylene blue and doubly stained with Ehrlich's methylene blue and aldehyde fuchsin. The surface coat was also stained with Gomori's ammoniacal silver and doubly stained with Gomori's ammoniacal silver and cationic iron colloid. The surface coat was usually expressed together with a nerve cell surface glycoprotein net detectable with lectin Wisteria floribunda agglutinin. These findings indicate that the perineuronal proteoglycan surface coat is identical to Cajal's superficial reticulum and contains some collagenous elements. It was further demonstrated that collagenase digestion erased Gomori's ammoniacal silver impregnation within the perineuronal proteoglycan surface coat.

While heat shock protein (HSP) 72 is known as a stress protein, there have been no reports of HSP 72 expression in patients who have undergone surgery for congenital heart disease. Fourteen patients (7 males and 7 females) who had undergone surgery for congenital heart disease were studied. The ages of the patients ranged from 2 months to 43 years old (mean 6.5 +/- 10.8 years old; median 3.0 years old). The diagnoses were Tetralogy of Fallot in seven, pulmonary atresia with ventricular septal defect (VSD) in three, complex anomalies in three, and VSD in one patient. Histological study and HSP analysis using Western blots and immunostaining with anti-HSP 72 monoclonal antibody were performed for right ventricular muscle samples resected during the surgery. The histological findings showed hypertrophic changes of ventricular cardiomyocytes in all samples studied. Western blots detected HSP 72 expression of various degrees in all specimens. Immunostaining using monoclonal antibody against HSP 72 showed that the protein was present in the nuclei and cytoplasm of cardiomyocytes. In conclusion, although it is difficult to determine the cause of the "stress" that triggers HSP 72 expression in cardiomyocytes, low O2 saturation and pressure overload might act as a "stress", and the only common factor that induced HSP 72 in every sample was hypertrophy.

We conducted Myanmar-Japan cooperation studies on hepatitis B and hepatitis C virus markers in patients with thalassemias and those with liver diseases. Among the 102 patients with liver diseases, 92% had a history of hepatitis B virus infection (antibody to hepatitis B core antigen positive), 35% were hepatitis B surface antigen positive, 39% were positive for anti-HCV. Among 28 patients with hepatocellular carcinoma, 46% had hepatitis B surface antigen, 21.4% had antibody to hepatitis C virus, and 7% were positive for both hepatitis B surface antigen and anti hepatitis C virus. The history of HCV infection among blood recipients at the Haematology Department of the Yangon General Hospital and at the Yangon Children's Hospital was found to be 55.5% and 46.7%, respectively, which is comparable to the history of hepatitis B infection (66.7% and 46.7%, respectively). This preliminary survey also encountered 2 cases positive for anti-HCV among 34 voluntary blood donors. This survey is the first one to report that hepatitis C is at the epidemic stage in Myanmar. As there is no effective treatment for hepatitis C in this country, a screening program for blood used in transfusion should be started immediately.

The effect of Blastocystis hominis (B. hominis) in both immunocompetent and immunocompromised subjects has been the subject of debate in recent years, mostly in response to its unknown pathogenicity and frequency of occurrence. We performed a non-randomised, open labelled, single institute study in our hospital in order to investigate the clinical significance and frequency of B. hominis in patients suffering from hematological malignancy (HM) who displayed symptoms of gastrointestinal diseases during the period of chemotherapy-induced neutropenia. The presence and potential role of other intestinal inclusive of parasites were also studied. At least 3 stool samples from each of 206 HM patients with gastrointestinal complaints (the HM group) were studied. These were compared with stool samples from a control group of 200 patients without HM who were also suffering from gastrointestinal complaints. Samples were studied with saline-lugol, formalin-ether, and trichome staining methods. Groups were comparable in terms of gender, age and type of gastrointestinal complaints. In the HM group, the most common parasite was B. hominis. In this group, 23 patients (13%) had B. hominis, while in the control group only 2 patients (1%) had B. hominis. This difference was statistically significant (P < 0.05). Symptoms were non-specific for B. hominis or other parasites in the HM group. The predominant symptoms in both groups were abdominal pain (87-89.5%), diarrhea (70-89.5%), and flatulence (74-68.4%). Although all patients with HM were symptom-free at the end of treatment with oral metranidazol (1,500 mg per day for 10 days) 2 patients with HM had positive stool samples containing an insignificant number of parasites (< 5 cells per field). In conclusion, it appears that B. hominis is not rare and should be considered in patients with HM who have gastrointestinal complaints while being treated with chemotherapy. Furthermore, metranidazol appears to be effective in treating B. hominis infection.

Conventional therapy for colorectal carcinoma using 5-fluorouracil (5-FU) has shown limited antitumor action. The purpose of our study was to investigate synergistic antitumor effects of the streptococcal preparation of OK-432 and 5-FU, and to elucidate the mechanisms of interaction between the 2 agents in mice. Biochemical modulation of OK-432 and 5-FU were determined in vivo against colon-26 carcinoma. The concentration of 5-FU and its metabolites, and the activity of thymidylate synthase and thymidine kinase, respectively, were measured using cytosolic extracts of the tumors. Combination treatment with OK-432 produced a significant increase in intratumor 5-FU and 5-FU in RNA (F-RNA) concentrations, increased the thymidylate synthetase inhibition rate, and decreased thymidine kinase activity, as compared with the results observed in the control mice. These additive antitumor effects are obtained by use of the 2 agents; the mechanism of action is considered to be the suppression of both the de novo and the salvage pathway for DNA synthesis, along with the suppression of RNA synthesis.

The majority of the t(14;18) chromosome translocations that occur in non-Hodgkin centroblastic-centrocytic follicular lymphoma can be detected by various methods. During the translocation process the bcl-2 gene located on chromosome 18 (18q21) is translocated to the JH region of the immunoglobulin gene of chromosome 14 (14q32). The most frequent type of bcl-2 translocations is the mbr type, whereas the immunoglobulin gene breaks mainly at the JH1-6 exons. About one of the 10(5) cells bearing the translocation can already be detected by using nested polymerase chain reaction (PCR). Eight patients suffering from follicular lymphoma were included in this study, which considered the usefulness of the PCR method. The results are in good agreement with those obtained by conventional diagnostic methods. Translocation can be detected, however, in patients with non-malignant diseases such as Sjogren's syndrome (about 5% of the patients) and in a patient with Whipple disease. In addition, translocation was detected in lymphocytes of peripheral blood of a healthy donor. Since lymphomas are detected in patients with Sjogren's syndrome with a relative high frequency, an early diagnosis of the translocation could improve the treatment of the disease. Nevertheless, a diagnosis of lymphoma is valid only in cases of bone marrow translocation-positivity.

Fracture of the penis is an unusual blunt traumatic injury of the erect penis. Twenty-five such cases, treated at the 2 main urological departments in the town of Varna between 1984 and 1999, were analyzed retrospectively. The average annual incidence in this series was 0.33 per 100,000 inhabitants. Most of the injuries occurred during vigorous sexual intercourse. Clinical diagnosis was mainly based on the patient's history and the physical findings. The diagnosis was verified by ultrasonography. In a few cases retrograde urethrography and cavernosography were used as additional diagnostic tools. Cavernosography was complicated by postprocedural priapism in 1 case. Unilateral tear of the corpora cavernosa was found in 24 cases. In 3 cases, partial (in 2) or complete (in 1) disruption of the corpus spongiosum and the urethra was found as well. The trauma was bilateral in 1 case in which 2/3 of the entire circumference of the penis was ruptured, including both corpora cavernosa and the urethra. Seventeen patients received immediate surgical repair. Most of them experienced an uneventful postoperative period with no serious consequences affecting their sexual function. Surgery was delayed in 6 and rejected in 2 cases. In all cases in which conservative (nonsurgical) management was the first treatment option, late complications (penile aneurysm, induration, penile curvature, erectile dysfunction) were observed and the final results were assessed as satisfactory or poor. We recommend immediate surgical treatment of all cases of penile fracture. Emergency surgical repair offers a chance for complete recovery and is the best method for providing a good functional prognosis.

Tacrolimus (FK-506) and cyclosporin A (CsA) are calcineurin antagonists used widely as T-cell immunosuppressants; however, their relative efficacy on the production of interleukin-18 (IL-18) remains undefined. We have examined the effects of FK-506 and CsA on the cytokine generation of human peripheral blood mononuclear cells (PBMCs) in mixed lymphocyte reaction (MLR) with lipopolysaccharide (LPS). We studied the levels of interleukin-18 (IL-18), IL-12, IL-10, IL-6, IL-2 and interferon-gamma (IFN-gamma) in the supernatant in allo-MLR by ELISA assay. Supernatant levels of IFN-gamma, IL-2, IL-6, IL-10 and IL-12 were detected 12 h after MLR and markedly increased thereafter. In contrast, production of IL-18 was detected at 12 h, reached a near maximum level at 24 h and decreased at 72 h. These results suggested that IFN-gamma production depended on IL-18, IL-12 and IL-2 in the early phase of MLR and depended mainly on IL-12 and IL-2 in the late phase. Both calcineurin antagonists inhibit the generation of IL-18, which plays a large role in allogeneic cell interactions, in macrophages and they also promote an equivalent down-regulation of T helper 1 (Th1) and Th2 responses in a concentration-dependent manner. About 90% of IFN-gamma production induced by MLR was inhibited by an anti-IL-18 antibody, showing that IL-18 can trigger IFN-gamma production in MLR. These results suggest that dual signaling consisting of antigen-driven nuclear factor of activated T cells (NFAT) activation and LPS-mediated NF-kappaB activation is crucial for IL-18 production in macrophages, and that IL-18 can trigger IFN-gamma production in T-cells by MLR.

It has been reported that Epstein-Barr virus (EBV) resides in resting B cells in vivo. However, an ideal in vitro system for studying EBV latent infection in vivo has not yet been established. In this study, a mantle cell lymphoma line, SP53, was successfully infected with a recombinant EBV containing a neomycin-resistant gene. The EBV-carrying SP53 cells were obtained by selection using G418. They expressed EBER-1, EBNAs, and LMP1; this expression pattern of the EBV genes was similar to that in a lymphoblastoid cell line (LCL). However, proliferation assay showed that the EBV-carrying SP53 cells have a doubling time of 73 h, compared with 57 h of SP53 cells. Transplantation of 10(8) SP53 cells to nude mice formed tumors in 4 of 10 mice inoculated, but the EBV-carrying SP53 cells did not. Unexpectedly, EBV infection reduced the proliferation and tumorigenicity of SP53 cells. However, the EBV-carrying SP53 cells showed higher resistance to apoptosis induced by serum starvation than did the SP53 cells. The inhibition of proliferation and the resistance to apoptosis induced in SP53 cells by EBV infection indicate that this cell line might to some extent provide a model of in vivo EBV reservoir cells.

Endoscopic biopsy is an important tool for histological diagnosis of lesions residing in gastrointestinal tracts. However, it is less useful in submucosal lesions due to the existence of normal overlying mucosa. We developed a new and safe technique for the diagnosis of submucosal tumor using Stiegmann-Goff endoscopic ligator. After removing surface mucosa to expose submucosal tissue by this method, conventional secured histological diagnosis could be performed. To determine definitive histological diagnosis, this technique is useful as well as Endoscopic Ultrasound (EUS) with fine needle aspiration biopsy and other modalities.

To find a new anti-malarial medicine derived from natural resources, we examined the leaves of 13 common Japanese plants in vitro. Among them, a leaf-extract of Hydrangea macrophylla, a common Japanese flower, inhibited the parasitic growth of Plasmodium falciparum. The IC50 of Hydrangea macrophylla leaf extract to Plasmodium falciparum was 0.18 microg/ml. The IC50 to NIH 3T3-3 cells, from a normal mouse cell line, was 7.2 microg/ml. Thus, selective toxicity was 40. For the in vivo test, we inoculated Plasmodium berghei, a rodent malaria parasite, to ddY mice and administered the leaf-extract of Hydrangea macrophylla (3.6 mg/0.2 ml) orally 3 times a day for 3 days. Malaria parasites did not appear in the blood of in the treated mice, but they did appear in the control group on day 3 or 4 after inoculation with the parasites. When leaf extract was administered to 5 mice 2 times a day for 3 days, malaria parasites did not appear in 4 of the mice but did appear in 1 mouse. In addition, the leaf-extract was administered orally 3 times a day for 3 days to Plasmodium berghei infected mice with a parasitemia of 2.7%. In the latter group, malaria parasites disappeared on day 3 after initiating the treatment, but they appeared again after day 5 or 6. Although we could not cure the mice entirely, we confirmed that the Hydrangea macrophylla leaf extract did contain an anti-malarial substance that can be administered orally.

In order to examine fatigue of the knee flexor and extensor muscles and to investigate the characteristics of muscular fatigue in different sports, a Cybex machine was used to measure muscle fatigue and recovery during isokinetic knee flexion and extension. Eighteen baseball players, 12 soccer players and 13 marathon runners were studied. Each subject was tested in the sitting position and made to perform 50 consecutive right knee bends and stretches at maximum strength. This was done 3 times with an interval of 10 min between each series. The peak torque to body weight ratio and the fatigue rate were determined in each case. In all subjects, the peak torque to body weight ratio was higher for extensors than flexors. Over the 3 trials, the fatigue rate of extensors showed little change, while that of flexors had a tendency to increase. In each subject, knee extensors showed a high fatigue rate but a quick recovery, while knee flexors showed a low fatigue rate but a slow recovery. As the marathon runners had the smallest fatigue rates for both flexors and extensors, we concluded that marathon runners had more stamina than baseball players and soccer players.

The present study was undertaken to investigate the postsynaptic effects of aminoglycosides on contractions evoked by acetylcholine (ACh), KCl, electrical field stimulation (EFS) and Na(+)- and Ca(2+)-free Ringer solution with 0.2 mM Na2 EDTA (NaFCaFR) in the isolated frog rectus abdominis. Neomycin inhibited contraction elicited by ACh, NaFCaFR, and EFS at the higher frequencies (8 and 10 Hz) but not those elicited by KCl and EFS at the lower frequencies (2, 3 and 5 Hz). D-tubocurarine inhibited ACh-induced contractions in a concentration-dependent manner. In addition, drug reduced EFS-evoked contractions to a limited extent. Lower concentrations (10(-5), 5 x 10(-5), 10(-4), 2 x 10(-4) and 3 x 10(-4) M) but not higher concentrations (4 x 10(-4) and 5 x 10(-4) M) of methoxyverapamil exhibited a concentration-dependent inhibitory action on NaFCaFR-induced contractions. Similar inhibitions of the same type of contraction were displayed by aminoglycosides (neomycin, streptomycin, netilmycin, gentamycin and amikacin). These results suggest that in addition to their antagonistic action on nicotinic receptors in the frog rectus abdominis, aminoglycosides may exert stabilizing effects on some functional components contributing to contractions at the membrane.

The purpose of this study was to verify the differences in women's anxiety in old age, the expected long-term care provision, and the expected final location for terminal care for the women themselves and for their parents. In addition, we examined factors that related to their anxiety and needs. The subjects were 1,000 women of the Seikatsu Club customer cooperative association in Chiba; 539 responded to our survey. The subjects were more anxious for their parents than for themselves. They more strongly expected long-term care for their parents to be provided by their family than they expected the same for themselves. Although no differences were observed in the expected location for terminal care, most subjects expected their home to be the terminal location. Analysis by the multiple logistic regression model indicated that the following factors were significantly related to the anxiety in old age: age odds ratio [OR = 1.81], employment [OR = 2.25] for women, and planning to live with parents [OR = 2.42], housing conditions [OR = 0.56] for parents. The following factors were significantly related to the expected long-term care provision: age [OR = 2.22] for women, and age [OR = 2.15], living with parents [OR = 3.58], and employment [OR = 2.33] for parents. Age [OR = 2.14] for women, and planning to live with parents [OR = 2.09] for parents were significantly related to the expected final location of terminal care. This survey showed that women expected long-term care for their parents to be provided by their family, while many expected public long-term care services for themselves. This is the biggest difference in women's outlook on long-term care for their parents and for themselves. Multivariate analysis suggested that women aged 40 years or over, who will need long-term care in the future, tended to expect public home care services for themselves. It is virtually certain that the demand for public home care services will increase in the future.

We investigated the presence of osteocyte apoptosis in the necrotic trabeculae of the femoral head of spontaneously hypertensive rat (SHR) using the in situ nick end labeling (TUNEL) method and transmission electron microscopy. The occurrence of osteonecrosis and ossification disturbance was significantly higher in SHR compared with Wistar Kyoto (WKY) rats, and Wistar (WT) rats used as control animals (P < 0.01). A high population of TUNEL positive osteocytes was detected mainly in 10- and 15-week-old SHRs. Sectioned examination of the femoral head of SHRs and WKY rats by electron microscopy revealed apoptotic cell appearances such as aggregation of chromatin particles and lipid formation. In contrast, a positive reaction was significantly lower in osteocytes in the femoral heads of WT rats (P < 0.01). Our results indicate that apoptosis forms an important component of the global pathologic process affecting the femoral head of SHR, which leads to osteonecrosis in this region.

Annexin was purified from rat liver mitochondria to an apparent homogeneity with a molecular weight of 35 kDa as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The purified mitochondrial annexin (AXmito) was identified as annexin I by an immunoblot analysis using anti-annexin I antibody. The inhibitory effect of AXmito I on porcine pancreatic phospholipase A2 activity was as potent as that of bovine lung annexin I. The presence of annexin I in mitochondria was confirmed by an electron-microscopic study. AXmito I was shown to be phosphorylated by intrinsic protein tyrosine kinases on its tyrosine residues. This annexin was also phosphorylated by protein kinase C.

The Thoratec (Vectra) polyurethane vascular access graft (TPVA) is among the most recent additions to the list of materials used to construct prosthetic grafts for vascular access during hemodialysis. We give the TPVA very high marks, and recognize the utility of such a graft for use in hemodialysis. However, the strong elasticity of this graft can lead to unexpected complications after suturing. We devised a new surgical method using a TPVA-ePTFE (expanded polytetrafluoroethylene) composite graft, substituting the anastomosis section of the TPVA with a portion of ePTFE graft material, and have been able to overcome most of the TPVA's potential problems. We herein describe the technique.

A sharp rise in the number of patients with infectious gastroenteritis was observed in the 25th week of year 1996 in the Takahashi-Ashin district by researchers with the Infectious Disease Surveillance Program for tuberculosis and other infectious diseases in the Okayama Prefecture. This sharp rise occurred coincidentally with an outbreak of enterohemorrhagic Escherichia coli O157:H7 (EHEC O157) infection in Niimi City of the Takahashi-Ashin district. However, this phenomenon of coincidental outbreaks was not observed during the outbreak of EHEC O157 infection in Oku Cho. By reviewing outpatients' charts in a sentinel hospital in Niimi City for the Infectious Disease Surveillance Program, it was noted that patients with acute gastrointestinal infection visiting the hospital during the increased incidence of infectious gastroenteritis may have been included as misclassified cases of EHEC O157 infection. On the other hand, the exponential probability plotting of symptomatic patients with EHEC O157 infection in Niimi City revealed a breaking point which suggested a dual exposure to contaminated food or an overlap with other acute gastrointestinal infections. The latter possibility was discounted, because stool culture-positive patients with EHEC O157 infection also exhibited a similar breaking point, and furthermore, the coincidental increase in infectious gastroenteritis in the same area was attributable to the EHEC O157 infection. The present study demonstrates the association between the sharp rise in gastroenteritis and the outbreak of EHEC O157 in the Takahashi-Ashin district. A careful analysis of the cases of infectious gastroenteritis by the Infectious Disease Surveillance Program would have predicted the outbreak of EHEC O157.

A study was conducted to analyze the distribution and diameter of muscle fiber types in samples of the medial paravertebral lumbar muscle, i.e., multifidus muscle, obtained from 76 patients who underwent surgery for disc herniation. The samples were compared with 41 control samples of corresponding muscle tissue taken from 41 young healthy subjects who had died a sudden death. Histochemical analysis of fibers associated with myofibrillar adenosine triphosphatase (ATPase) revealed the presence of Type I fibers (slow-twitch fibers) and of Type IIA and IIB fibers (fast-twitch fibers) in both the experimental and control samples. The respective percentage of muscle fibers was calculated and their diameters were measured. Type I fibers predominated in both groups and were significantly larger in diameter than Type IIA and IIB fibers. Both fast-twitch fiber types were distributed in almost equal proportions in the healthy women. In the healthy men, Type IIA fibers prevailed. In the healthy females, the percentage of Type I fibers was found to be slightly higher than in the males, but the diameter of all fiber types was respectively smaller. In the females who had undergone surgery, Type I fibers were significantly larger in diameter than those of the healthy subjects. On the other hand, the diameters of all muscle fiber types were significantly larger, and the percentage of both fast-twitch fibers were Idwer in the samples from men who underwent surgery, as compared to the healthy tissue samples. The morphometric changes in the multifidus muscle at the level of the protruded disc observed by the histochemical method for demonstration of myofibrillar ATPase could not be related to the compressed nerve root in the majority of cases in our study.