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We constructed a plasmid, pBH103-ME5, in which the region encoding the 10 preS2 amino acid residues and the S domain of the hepatitis B surface antigen (HBsAg) were regulated by the promoter of the yeast repressible acid phosphatase gene. Saccharomyces cerevisiae carrying pBH103-ME5 produced the HBs antigen (yHBsAg), when it was cultured in a medium containing a low concentration of phosphate. The antigen was purified to homogeneity. Its molecular weight was determined by Western blotting to be 24,000, and its amino acid composition agreed well with that deduced from the nucleotide sequence. The C-terminal amino acid sequence of yHBsAg was exactly the same as that predicted from the nucleotide sequence, while the N-terminal amino acid acetylserine, which was followed by 8 amino acid residues coded by the preS2 region. These results indicate that the recombinant yeast produced a single polypeptide consisting of the preS2 region and the subsequent S domain after being processed at the N-terminus

Pulmonary function tests were performed on 252 healthy young subjects free from respiratory and allergic symptoms, and 80 young subjects with past history of nasal allergy (PNA) and 10 subjects with past history of bronchial asthma (PBA). All the subjects were non-smokers. Maximal expiratory flow-volume (MEFV) curves were visually classified into five types (A-E). The percent distribution of type A in healthy subjects was significantly higher than in the PNA group, while the total sum of percentage of types B, C, and D in the PNA group was significantly higher than in the healthy subjects. The percent distribution of type E in the PNA group was similar to that in the healthy subjects. The percent distribution of MEFV types were significantly different between healthy males and healthy females. The percent distribution of types A, B and E were the highest in healthy subjects, PNA and PBA groups, respectively. Conclusively, the difference in the percent distributions of MEFV types was recognized among healthy subjects, PNA and PBA groups.

Antroduodenal contractions were studied in rat preparations. Augmented duodenal contractions occurred spontaneously in coordination with antral contractions in normal and saline-pretreated preparations. The coordination did not occur when muscle layers and the myenteric plexus were transversely cut at the duodenum just anal to the gastroduodenal junction. In silent preparations, the coordinated contractions were produced by neostigmine or domperidone. When the antroduodenal junctional zone was pretreated with benzalkonium chloride, the augmented duodenal contractions did not occur spontaneously, and even after administration of neostigmine and domperidone although antral contractions occurred spontaneously. In these preparations, there were notably few myenteric neurons in the junctional zone, but the neurons were distributed normally in the areas where motility was recorded. The results suggest that myenteric neurons mediate antroduodenal coordinated contractions and that the coordination is modified by myenteric cholinergic excitatory and dopaminergic inhibitory pathways.

Post-traumatic colonic stenosis (obstruction) is rare. We experienced a case of sigmoid obstruction due to blunt abdominal trauma. A 75-year-old man was hit on the lower abdomen 3 days before admission and gradually developed abdominal pain and distension. Laboratory data showed severe inflammation and a barium enema disclosed obstruction of the sigmoid colon. Conservative treatment was carefully carried out, because there was no sign of peritoneal irritation and there were passages of normal stool and flatus. The sigmoid obstruction gradually improved and the stenosis was almost undetectable on a barium enema on the 51st hospital day. An abdominal contusion is the most likely causal factor in this case. Compression of the sigmoid colon between the abdominal wall and the promontory of the pelvis is the most possible explanation.</P>

The hepatitis B virus surface antigen containing the preS2 nine amino acid sequence produced by a recombinant Saccharomyces cerevisiae (yHBsAg) was purified and its physicochemical properties were determined. Ultrastructurally, the yHBsAg was found to be a homogeneous spherical particle with a diameter of 24 +/- 4 nm. The homogeneity of the yHBsAg particles was also demonstrated by analyses of their buoyant density and isoelectric point. They consisted of protein (53%), lipid (36%) and carbohydrate (11%), and the alpha-helix content was estimated to be 32%, differing from the reported values for human plasma-derived HBsAg (hHBsAg). Immunodiffusion analysis showed that the antigenic specificity of yHBsAg was identical to that of hHBsAg. Immunization of mice demonstrated that the immunogenicity of the yHBsAg was significantly higher than that of hHBsAg.

<p>We present a case of pre-elastofibroma-like lesion, a kind of elastic-producing fibrous tumor. The small colonic polyp, which was found in a 49-year-old asymptomatic man in association with a large colonic adenoma, showed submucosal nodular deposits of fine granular or fibrillar eosinophilic materials with interspersed fibroblastic cells. Elastic stain revealed these deposits to consist mainly of dark gray granular or partially fibrillar dense elastinophilic materials, most of which were digested with elastase. This stromal lesion somewhat resembled a pre-elastofibroma. Therefore, pre-elastofibroma-like lesions should be kept in mind as a possible origin of colonic polyp.</p>

In order to elucidate the mechanism of latent infection of herpes simplex virus (HSV), reactivatable latency of three avirulent strains (SKO-1B, -GCr Miyama, SKa) of HSV type 1 was comparatively examined in a mouse latency model. The SKO-1B strain showed high rate of virus reactivation from explanted trigeminal ganglia without n-butyrate enhancement, while the other two strains showed a very low rate of virus reactivation in the absence of n-butyrate. In the presence of n-butyrate, however, the rate of the -GCr Miyama strain jumped to a comparable level with that of SKO-1B, although the rate of SKa remained at a low level. A more precise follow-up experiment changing the virus dose highlighted the difference of the ability to reactivate from the latent state between SKO-1B and -GCr Miyama. Virus titer in trigeminal ganglia during acute phase, infectivity to cell lines of neural origin, and susceptibility to acyclovir and phosphonoacetate were assayed to know the reasons for the variation in the ability of reactivatable latency among these strains. It was concluded that the reduced infectivity to neural cells, and limited ability of reactivatable latency shown by the SKa strain could mainly be attributed to the deficiency of thymidine kinase activity.</P>

The association between the extent of left ventricular (LV) hypertrophy and severity of ventricular or atrial arrhythmias are examined. Two-dimensional echocardiography and 24-h Holter electrocardiography monitoring were performed in 60 patients with hypertrophic cardiomyopathy (HCM). According to the distribution of the LV hypertrophy, the patients were divided into three groups: 1. Apical hypertrophy (APH), 2. Septal hypertrophy, and 3. Extensive hypertrophy. Ventricular arrhythmias were found in 82% of the patients and supraventricular arrhythmias were detected in 70% of the patients. Lown grade III and IV arrhythmias occurred significantly more frequently in patients with extensive than with septal hypertrophy. Lown grade III to IV arrhythmias did not occur in patients with APH. Present results show a significant association between the extent of LV hypertrophy and the severity of ventricular arrhythmias in HCM. </P>

Determination was made of step length, stride width, time factors and deviation in the center of pressure during up- and downslope walking in 17 healthy men between the ages of 19 and 34 using a force plate. Slope inclinations were set at 3, 6, 9 and 12 degrees. At 12 degrees, walking speed, the product of step length and cadence, decreased significantly (p less than 0.01) in both up- and downslope walking. The most conspicuous phenomenon in upslope walking was in cadence. The steeper the slope, the smaller was the cadence. The most conspicuous phenomenon in downslope walking was in step length. The steeper the slope, the shorter was the step length.

Dynamic CT scans were conducted on 94 persons who had been randomly selected among the patients and the volunteers. The test results were used to obtain the time-density curve. A part of the subjects (20 cases) underwent the renogram examination for the comparative studies. The cortico-aortic (CA) ratio derived from the time-density curve demonstrated good correlation between the dynamic CT and the renal function (r = 0.68). When the dynamic CT studies and the renogram were compared, the vascular phase of the renogram showed strong correlation with CA ratio. Consequently the dynamic CT study the CA ratio was believed to demonstrate the renal function.

The cardioprotective effect of calmodulin antagonists, trifluoperazine (TFP) and N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7) was examined on the isolated rat heart exposed to hypothermic and ischemic conditions by measuring distribution of lysosomal enzymes in myocardial cells, and leakage of creatine kinase (CK) during reperfusion and postischemic recovery in myocardial systolic function. Experimental hearts were infused with 20 degrees C Krebs-Henseleit bicarbonate buffer (KHB) or KHB containing TFP or W-7 for 2min every 30min during hypothermic ischemia. After ischemia for 120min at 20 degrees C, rat hearts were reperfused at 37 degrees C for 30min. TFP and W-7 improved functional recovery and prevented CK release. In TFP treated hearts, leakage of lysosomal enzymes was reduced significantly, whereas stabilization of lysosomes by W-7 did not occur. These results suggest that calcium-calmodulin dependent enzymes may play an important role in the development of cellular damage of the myocardium during hypothermic ischemia, although levels of leakage of lysosomal enzymes may be unreliable predictors of functional recovery after hypothermic ischemia.</P>

A monoclonal antibody (MAb), OPT1, reactive with T cells in formalin-fixed, paraffin-embedded tissue sections, has been identified through immunization with activated T cells from peripheral blood lymphocytes (PBL). The antibody is an IgG1 antibody as demonstrated by the Ouchterlony technique. By cytofluorometric analysis, almost all CD3+ lymphocytes and only a few CD20+ lymphocytes of peripheral blood expressed the OPT1 antigen. Nonhematolymphoid cell lines were negative for OPT1 by the immunoperoxidase staining using acetone-fixed cell lines. On the contrary, peripheral T cells, cells of two T cell lines out of four and a part of the cells of one B cell line out of two were positive for OPT1. The immunoperoxidase staining of paraffin-embedded tissue sections revealed that most of lymphocytes in T cell areas of lymph nodes expressed OPT1 antigen. Some lymphocytes in both cortex and medulla of the thymus and erythroid precursors of the bone marrow were OPT1+. In the malignant lymphoma series, approximately 90% of T cell lymphomas and 6% of B cell lymphomas reacted with OPT1. None of the Reed-Sternberg cells nor Hodgkin cells in Hodgkin's disease were positive. Consequently, OPT1 may be useful for the diagnosis and study of malignant lymphomas and other related lesions.</P>

The role of alpha-1 adrenergic mechanism in the shaking stress-induced adrenocorticotropic hormone (ACTH), and plasma noradrenaline secretion and pressor response were investigated using conscious rats. We also studied whether or not central corticotropin releasing hormone (CRH) is involved in the shaking stress-induced ACTH secretion. The shaking stress caused significant elevations of plasma ACTH, noradrenaline, and systolic blood pressure. Intra-third ventricular administration of alpha-1 adrenergic blocker, bunazosin, inhibited the shaking stress-induced ACTH secretion, but did not alter stress-induced noradrenaline secretion and pressor response. Furthermore, intra-third ventricular administration of CRH antagonist, alpha-helical CRH, significantly attenuated stress-induced ACTH secretion. These results indicate that alpha-1 adrenergic pathway and CRH at least partly mediate the shaking stress-induced ACTH secretion.</P>

We studied the pathways of complement activation associated with the islet cell surface antibody (ICSA) obtained from sera of 7 patients (age less than 15 years) with insulin dependent diabetes mellitus (IDDM). The target cells were 51CR labelled rat islet cells and the complement source was human AB serum. Complement-dependent antibody mediated cytotoxicity (CAMC activity) was obtained using the percentage of cytotoxicity. CAMC activity of untreated sera was significantly inhibited by treating with EGTA or EDTA (p less than 0.001). The CAMC activity of EDTA-treated sera was significantly lower than that of EGTA-treated sera (p less than 0.001). In the inactivated human AB serum, it was lower than that of EGTA-treated sera (p less than 0.05), but not different from that of EDTA-treated sera. These results show that the complement activation associated with ICSA in patients occurred not only via the classical pathway but also via the alternative pathway.

Previously, we pointed out the importance of the kynurenine metabolism in fetuses and neonates. We examined localization and developmental change of indoleamine 2,3-dioxygenase activity in human placenta. The indoleamine 2,3-dioxygenase was found localized in syncytiotrophoblast in the placenta. The indoleamine 2,3-dioxygenase activity was not detected in placenta in the early stage of gestation. It was first detected at around 14 weeks of gestation, increased rapidly thereafter and was maintained at high levels till near term. The indoleamine 2,3-dioxygenase activity was significantly lower in placenta with retarded intrauterine development. These results suggest the importance of placental indoleamine 2,3-dioxygenase during fetal development.</P>

<P>The tissue concentration of doxorubicin (adriamycin; ADM) and its major metabolite (aglycone I) was examined in mice pretreated with alpha-tocopherol (VE) or coenzyme Q10 (CoQ). In VE-pretreated group, the concentrations of aglycone I of the liver (1, 3 and 5 h after the administration), kidney (1 and 3h) and heart (3h) were significantly higher than those in the saline group. The clinical application of VE or CoQ concomitant with anti-tumor drugs especially ADM, requires caution.

<P>Peripheral T-cell lymphoma (PTL) is a distinctive clinical entity, albeit it comprises several diseases with histologically heterogeneous diagnoses. We studied prognostic factors on 30 patients diagnosed and treated at Shikoku Cancer Center Hospital. Clinical findings and laboratory data were evaluated by statistical analysis to investigate the important factors influencing survival duration. Variables influencing survival were stage, leukemic change, bone marrow infiltration (BMI), anti-human T-lymphocyte virus-type I antibody, white blood cell count, and lactate dehydrogenase (LDH). Multivariate analysis revealed high level of LDH and positive BMI as the important factors for short survival. Histological classifications of the Working Formulation and the T-lymphoma classification by Suchi et al. were also evaluated whether these were related with prognosis. Our data revealed that there was no significant relationship between histological subtype and survival duration. The study of prognostic factors provides valuable aids for us to understand the clinical characteristics of PTL patients with various backgrounds.

In order to clarify difference of the mucosal immunity in various sites of normal large and small intestines, we studied the population of lymphocyte subsets and immunoglobulin (Ig)-containing cells in situ in biopsy specimens taken from various sites (ascending colon, sigmoid colon and rectum) of the large intestine and from the duodenum using an immunohistochemical method. Monoclonal antibodies against pan-T (Leu 1), cytotoxic/suppressor T (Leu2a), helper/inducer T (Leu3a), suppressor T (Leu15) and natural killer/K (Leu7) cells, and polyclonal antibodies to human IgG, IgA and IgM were used. In the duodenum, intraepithelial lymphocytes (IELs) were more prominent than in the large intestine. Immunoelectron microscopic observation revealed that some Leu2a+ IELs possessed pseudopods extending into intestinal epithelial cells, indicating that some IELs belong to the cytotoxic T cell subset. Leu7+ IELs were scarcely observed and Leu7+/Leu1+ ratio was higher in the large intestine than in the duodenum. Furthermore, the number of Leu7+ cells were more in the distal than the proximal colon. In the lamina propria Ig-containing cells tended to be fewer in the rectum than in the duodenum and the proximal colon. Our findings may suggest the variation of local immune responses and the difference of assigned immunological functions among the various sites of the intestines.

Some mechanisms to reduce methemoglobin (metHb) formation for the maintenance of normal oxygen transport have been proposed. To study the role of catalase (EC 1.11.1.6), metHb formation in the hemolysate of normal and Japanese acatalasemic human subjects were examined spectrophotometrically. Significantly increased level of metHb was induced by potassium ferrocyanide in the hemolysate of acatalasemic subject. The addition of catalase reduced the metHb formation, while 3-amino-1,2,4-triazole (AT), a specific inhibitor of catalase-H2O2 compound I, increased it. These results obtained from human subjects were well consistent with those from mice and suggested that catalase plays a role in protecting erythrocytes against metHb formation.

We investigated the antitumor activities of 5-fluorouracil (5-FU), 5'-deoxy-5-fluorouridine (5'-DFUR), 1-hexylcarbamoyl-5-fluorouracil (HCFU) and 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT-207) in combination with hyperthermia in vitro. The antitumor effect of 5-FU (10(-4) M) was slightly enhanced by combination with hyperthermia (42 degrees C) for 2h, and the effect was determined to be additive. Synergistic enhancement of antitumor activity was obtained by the concurrent use of hyperthermia (42 degrees C, 2h) and 5'-DFUR (10(-4) M) or HCFU (10(-5) M). However, the antitumor effect of FT-207 (10(-4) M) in combination with hyperthermia was comparable that of hyperthermia alone. The synergistic enhancement of antitumor activity was not obtained for all drugs when the cells were preheated at 42 degrees C for 2h. On the other hand, when cells were pretreated with drugs before heat exposure, weak interactions were obtained after 5-FU and 5'-DFUR treatment, and a synergistic interaction was obtained after HCFU treatment. It is speculated that the metabolites of 5'-DFUR and HCFU enhance the cytotoxicity of 5-FU, or might change the threshold concentration for a cytotoxic effect of 5-FU in cancer cells.