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Epstein-Barr virus (EBV), or human herpesvirus 4 (HHV-4), infects the vast majority of adults worldwide, and establishes both nonproductive (latent) and productive (lytic) infections. Host immune responses directed against both the lytic and latent cycle-associated EBV antigens induce a diversity of clinical symptoms in patients with chronic active EBV infections who usually contain an oligoclonal pool of EBV-infected lymphocyte subsets in their blood. Episomal EBV genes in the latent infection utilize an array of evasion strategies from host immune responses: the minimized expression of EBV antigens targeted by host cytotoxic T lymphocytes (CTLs), the down-regulation of cell adhesion molecule expression, and the release of virokines to inhibit the host CTLs. The oncogenic role of latent EBV infection is not yet fully understood, but latent membrane proteins (LMPs) expressed during the latency cycle have essential biological properties leading to cellular gene expression and immortalization, and EBV-encoded gene products such as viral interleukin-10 (vIL-10) and bcl-2 homologue function to survive the EBV-infected cells. The subsequent oncogenic DNA damage may lead to the development of neoplasms. EBV-associated NK/T cell lymphoproliferative disorders are prevalent in Asia, but quite rare in Western countries. The genetic immunological background, therefore, is closely linked to the development of EBV-associated neoplasms.

FKHRL1 (FOXO3a), a member of the Forkhead family of genes, has been considered to be involved in the development of breast tumors; however, the in vivo expression and activation status of FKHRL1 in breast tumors still remains unclear. We immunohistochemically demonstrated the expression and intracellular localization of FKHRL1 in human breast tumors by the novel anti-FKHRL1 antibody which is available for formalin-fixed paraffin-embedded specimens. In a total of 51 cases of benign tumors, FKHRL1 was diffusely expressed in all cases, and its intracellular localization was revealed to be cytoplasmic (inactive form) in 94% of cases of intraductal papillomas (16/17) and 91% cases of fibroadenomas (31/34), with a similar pattern to normal glandular epithelium. In invasive ductal carcinomas, 83% of the cases (93/112) diffusely expressed FKHRL1; however, unlike benign tumors, 71% of the cases (66/93) showed the nuclear-targeted, active form of FKHRL1. Moreover, activated FKHRL1 was predominantly observed in scirrhous (29/36, 81% of the cases) and papillotubular (30/38, 79% of the cases) subtypes, compared to the solid-tubular subtype (7/19, 37% of the cases). Furthermore, the cases with nuclear-targeted FKHRL1 showed a tendency to have lymph nodal metastasis with statistical significance (P < 0.0001). Thus, the activation of FKHRL1 seems to be recognized as one of the specific features of invasive ductal carcinoma of the breast.

Muscle power in the lower extremities and body sway were measured in 57 healthy young women volunteers in their 20's. Body sway was measured with a stabilimeter for 30 sec during two-leg standing, and for 10 sec during one-leg standing with the eyes open or closed, alternating between right and left legs (5 times each). The measured parameters of body sway were locus length per time unit, locus length per environmental area, environmental area, rectangle area, root mean square area, and the ratio of sway with eyes closed to sway with eyes open. Knee flexor and extensor power and toe flexor and abductor power were the measures representing lower extremity muscle power. The increase in sway with the eyes closed was more marked during one-leg standing than two-leg standing, as expected. We found that 36 of 57 subjects (62%) were unable to maintain one-leg standing with their eyes closed, and this failure correlated with marked body sway (P = 0.0086). Many subjects had one leg that was classified as stable and the other leg classified as unstable. Clearly, testing of both legs alternately with eyes closed is necessary to measure the full range of sway in subjects. Lower extremity muscle power did not appear to be the dominant factor in maintaining balance in these young subjects.

Protein transduction therapy using poly-arginine peptide can deliver the biologically active proteins. A previous study showed that 11 poly-arginine fused p53 protein (11R-p53) effectively penetrated across the plasma membrane and inhibited the proliferation of oral cancer cells. However, the intracellular half-life of the delivered protein was less than 36 h. Previous studies also showed that 2-methoxyestradiol (2-ME), an endogenous non-toxic estrogenic metabolite, induces the stabilization of the wild-type p53 protein in human cancer cells posttranscriptionally. In the present study, we examined whether 2-ME induced the stabilization of 11R-p53 and had an inhibitory effect on the proliferation of oral cancer cells. The application of 2-ME significantly enhanced the inhibitory effect of 11R-p53 on the proliferation of oral cancer cells. However, 2-ME had no effect on the intracellular half-life of 11R-p53 in oral cancer cells. Of interest is the finding that 2-ME suppressed the transcriptional activity of NFkappaB, which has an important role in tumorigenesis, but did not affect p53 transcriptional activity. These results suggest that 2-ME synergistically enhances the 11R-p53-induced inhibition of the proliferation of oral cancer cells through the suppression of NFkB transcription.

A 68-year-old Japanese man with a history of linitis plastica carcinoma of the stomach and subsequent gastrectomy 8 years previously presented with lower abdominal pain. Radiological and endoscopic examinations showed multiple submucosal nodular lesions similar to Crohn's disease in the ileocecal area. A firm diagnosis could not be made after initial multiple biopsies. Finally, a submucosal biopsy revealed adenocarcinoma. The ileocecal lesion was diagnosed as a recurrence because of the histological findings, which included mucosal preservation, a similarity with the histologic type of stomach carcinoma, and atypical immunoreactivity for primary colon carcinoma; the lesion was negative for both cytokeratin 7 and cytokeratin 20. In cases where metastatic carcinoma of the colon is suspected, we recommend early consideration of a submucosal biopsy.

Ureteroscopy has evolved in many aspects, particularly in the flexibility and size of ureteroscopes. We have developed a new detachable access sheath to make ureteroscopic procedures more straight-forward and to reduce possible damage to delicate instruments used in the procedure.

Levamisole was administered to 177 patients with gastrointestinal cancer (88 curative resection, 58 noncurative resection and 31 without resection). It was administered at a daily dose of 150 mg for three consecutive days every other week. The administration was started, as a rule, 3 days before operation. This medication was repeated as frequently as possible at least for one month. The cellular immunity and 18-month survival rate of treated and control groups were compared. Levamisole effectively improved peripheral lymphocyte blastformation against phytohemagglutinin and increased the numbers of peripheral blood lymphocytes. Levamisole caused extremely high blastformation rates, in general, enhanced PPD reactions in non-curative resection cases 7 months after operation and showed no influence upon the number of peripheral blood lymphocyte. The effect of levamisole on the 6-month survival rate was most marked in patients without resection. Increased 12-month survival rate was marked in non-curative resection cases and, to a lesser extent, curative resection cases. Patients without resection had a slightly improved 12-month survival rate. Levamisole improved the 18-month survival rate in resectable cases; however, there were no significant differences in 18-month survival between levamisole and control groups of patients not undergoing resection. The results suggest that levamisole is effective in the patients whose tumor cells have been decreased by any method.

Sera from 84 patients with chronic liver disease [CLD] (74 chronic active) and from 53 blood donors were tested immunochemically for anti-liver cell membrane antibody (LMAb). LMAb to rat liver tested by an indirect immunofluorescent technique was positive in 53.3% of CLD patients with positive HB surface antibody (HBsAb) and 40.0% of HBsAb positive blood donors. Pepsin digestion of the sera indicated that the binding between liver cell membrane and IgG was at the Fc site on the immunoglobulin. The sera with positive LMAb from HBsAb positive blood donors had elevated Clq-binding activity (Clq-BA). The LMAb to rat liver was a macro-molecular IgG (19-22S IgG) when assayed by Sephadex G-200 column chromatography and 5-40% sucrose density gradient ultracentrifugation. The results suggest that the LMAb in serum from a patient with chronic active liver disease may be an immune complex which consists of various antigens such as HB virus and its antibodies in serum.

The mechanism of cell dissociation with trypsin and EDTA was examined. Cell dissociation was possible when trypsin and EDTA were given simultaneously, when trypsin was given after EDTA treatment, but not when trypsin was given before EDTA treatment.

Fifteen cases of keratoconjunctivitis sicca (KCS) of unknown etiology were treated with soft contact lenses for the purpose of their bandage effects and moisuture supply. A soft contact lens was worn on one of the eyes of each case but not on the other to compare its effectiveness. New opthalmic drops or contact lens wearers were dropped in both eyes. Furthermore, the KCS-index was worked out on the basis of the complaints of 23 patients of KCS of unknouwn etiology. The indexes before and after treatment were compared. Corneal objective findings were improved in all the eyes wearing soft contact lensen for along period, and seven stopped wearing them although corneal objective findings were much better, because they had some troubles with handlings were much better, because they had some troubles with handling the lenses, because they had lost rhem, or because their visual acuity decreased while wearing the lenses. Forlong term wearing the flattest lenses should be used in the beginning and changed gradually to lenses of greater curvature which are better able to keep their centering. Then immediately after successful fitting, the lenses should be given appropriate refractive power. The new ophthalmic drops for soft contact lens wearers were very much effective as artificial tears to both eyes with and without sofy contact lenses. KCS-indexes were numerical values relating to patients subjective symptoms. KSC-indexes improves by an average of +6.4±7.5 after treatment. On the other hand, KCS-indexes improved by +10.7±7.9 in the group that succeeded in wearing SCL for a long period, and by +7.6±2.1 even in the group that failed.

Human leukemic B-cell (BALL-1), T-cell (TALL-1) and null-cell (NALL-1) lines have been established from three patients with acute lymphoblastic leukemia (ALL). To study the heterotransplantability and in vivo growth characteristics, attempts were made to transplant these ALL cell lines into newborn Syrian hamsters treated with rabbit anti-hamster thymocyte serum. Intraperitoneal implantation of 1.8-3.5 x 10(7) cells gave rise to invasive tumors in all recipients after 15 to 41 days. In addition to a common in vivo feature of mesenteric and retroperitoneal tumors, BALL-1 line was characterized by infiltration of the skin, massive ascites and bone marrow invasion. TALL-1 cells infiltrated various organs including the lymph nodes, liver, gallbladder, spleen, bone marrow, central nervous system and eyes. NALL-1 line grew slowly, producing the least tumors, although there were distant metastases in the lungs. Tumor cells were detected in the blood of 2 of 3 BALL-1-bearing hamsters and in the blood of 4 of 5 TALL-1-bearing hamsters. Thus, these three ALL cell lines were found to exhibit a characteristic biological behavior in hamsters, which might be related to the different cell lineage.

Myxofibroma is a rare tumor. Three cases of myxofibroma, each of which developed at the right mandibular ramus, mandibular anterior tooth region, are presented. Myxofibroma developing in the mandibular ramus region is rare, and there has been only one case reported so far in Japan.

Sprague-Dawley rats given azathioprine in the diet for 3 to 4 weeks developed severe liver damage. Elevations of serum alkaline phosphatase and gamma-glutamyl transpeptidase activities were associated with increased hepatic glucose 6-phosphate dehydrogenase levels and decreased liver glucose 6-phosphatase activities, i.e., conditions which were commonly observed in various hepatotoxin-induced liver injuries. Light and electron microscopic observations revealed centrolobular necrosis with large scars and the proliferation of the mitochondria and rough endoplasmic reticulum. This model could be used to study the mechanisms of azathioprine-induced liver damage and its prevention.

A report is made of a 52-year-old male whose main complaint was a painless tumor at the right side of the palate resulting in speech disturbance. He was diagnosed as a case of what Stout called benign mesenchymoma. Some discussion is also made of the tumor pathology in terms of genetic factors, predirective sites, age range, sex differences and therapy.

A case of a 40-year-old woman who was suffering from painless thyroiditis with recurrent transient thyrotoxicosis is reported. Acute exacerbations occurred four times during the past ten years, two after delivery and two after catching a cold. Serum thyroid hormones increased, though radioiodine uptake by the thyroid was very low and no inflammatory signs were observed. The histological findings of the thyroid were of atypical thyroiditis and not consistent with either chronic lymphocytic thyroiditis or subacute thyroiditis. Tanned sheep red cell hemagglutination titers for anti-thyroglobulin antibodies (TRC) and for anti-microsomal antibodies (MHA) were negative or low. The disease seems to be rare and the pathophysiology and etiology are discussed.

A variety of polymeric materials (polyurethane, polypropylene, polyethylene and polyvinylidine copolymer) have been evaluated for suitability in making of air-filled balloon to detect intraluminal pressure. The polyurethanes, in particular ECD, proved to be most suitable because of the ease of fabrication, low permeability to air and high frequency characteristics. Polyvinylidine copolymer was adequate but suffered from difficulties in fabrication. Polypropylene and polyethylene, available in film, were troublesome in making balloon and displayed low frequency characteristics.

The level of blood catalase activity in heterozygotes for Japanese type acatalasemia was demonstrated to be about half of normal levels by means of titration and spectrophotometric methods. A distribution plot of catalase activities in heterozygous blood was completely separate from that of normal blood. Comparative analysis of the partially purified erythrocyte catalase preparations obtained from normal and heterozygous individuals revealed no distinct differences between them regarding stability to heat, sodium dodecyl sulfate and some enzyme inhibitors or pH dependency. The erythrocyte catalase in heterozygotes for Japanese type acatalasemia contains about half the normal specific activity and as stable as that in normal individuals.

A permeable cell system for studying RNA synthesis was established. Mouse ascites sarcoma cells were made permeable to nucleoside triphosphates and alpha-amanitin by treating with a hypotonic buffer. Separate determinations of endogenous RNA polymerase I, II and III activities in permeable cells were conducted using the different sensitivities of these enzymes to alpha-amanitin. The endogenous activity of RNA polymerase II under optimal conditions was one tenth of total RNA synthetic activity in isolated nuclei, and one third of that in permeable cells. The extremely low ratio of RNA polymerase II activity to total RNA synthetic activity in isolated nuclei was thought to be caused by increase of RNA polymerase I activity and decrease of RNA polymerase II activity. These and other results suggested that RNA synthesis in permeable cells reflects more precisely the in vivo state of RNA synthesis than thatin isolated nuclei. The permeable cell system will provide a useful method for studying the separate activities of RNA polymerases I, II and III in situ.

Cellular stimulating factors on cell proliferation in the supernatants of chick embryo carcases and adult muscles were studied. There were plural stimulating factors in embryonic and adult muscular supernatants that promoted cell proliferation without any supplement of sera and other materials. Salting-out methods with ammonium sulfate, ethanol fractionation, and isoelectric precipitation were used to isolate the stimulating factors, and these three methods proved the presence of plural stimulants on cell proliferation in the supernatants of chick embryo and adult muscles. The stimulants had altered physico-chemical properties and biological activities due to embryological development. The embryonic stimulants enhanced the synthesis of DNA and protein remarkably, and RNA synthesis in whole cell systems slightly. The muscular stimulants enhanced protein synthesis without any stimulation of DNA and RNA synthesis. Partial purification of the stimulants from the ethanol fractions was performed by DEAE-cellulose chromatography and Sephadex gel chromatography.

A sequential radioimmunoassay procedure for unconjugated and conjugated estrone, estradiol-17 beta and estriol in male human plasma was developed. The blank values in this assay for unconjugated estrone, estradiol-17 beta, estriol conjugated estrone, estradiol-17 beta and conjugated estriol were 0.36 +/- 1.14 pg, 3.90 +/- 2.75 pg, 2.25 +/- 2.08 pg, 0.92 +/- 1.51 pg, 5.02 +/- 2.86 pg and 3.12 +/- 2.97 pg, respectively. Mean values of unconjugated estrone, estradiol-17 beta, estriol, conjugated estrone, estradiol-17 beta and conjugated estriol in plasma from 28 normal adult males were 38.4 +/- 13.4 pg/ml, 32.6 +/- 9.90 pg/ml, 4.06 +/- 3.68 pg/ml, 34.2 +/- 13.8 pg/ml, 40.4 +/- 12.3 pg/ml and 31.8 +/- 7.41 pg/ml, respectively. Both unconjugated and conjugated estrogen levels in patients with liver cirrhosis were elevated and conjugated estrogen, especially estriol levels, in patients with renal insufficiency were markedly elevated.