Search

Healthy subjects 40 years old were used as controls in a study of stellate cells (S-100 protein-containing cells, or S-100 cells) in subjects with chronic alcoholism and fatty liver or fatty cirrhosis. S-100 cells were sparsely found in the adenohypophysis of control subjects, and these cells sometimes formed small clusters. However, in chronic alcoholics with fatty liver or fatty cirrhosis, the number of stellate cells in the anterior pituitary tended to be 17 times higher than it was in the control group. No increase in the number of S-100 positive cells that constitute the large and small follicles in the intermediate pituitary. The physiological function of the S-100 protein has not yet been identified. The fact that an increase in prolactin-secreting and growth hormone-secreting cells, as well as a decrease in gonadotrophs were observed in the hypophysis of alcoholics suggests that the function of stellate cells may be closely related to these phenomena. Our results also imply that the stellate cells found in the anterior and intermediate pituitary differ in function although they both produce S-100 proteins.

Urethral duplication is a rare congenital anomaly. Although a number of theories have been proposed to describe the embryology of the condition, the actual mechanism of the disorder is still unclear. We report here a case of urethral duplication in a 11-year-old boy complaining of a double stream, and review the current literature on this rare entity.

In this study we used paraffin-embedded human pituitary obtained from 248 autopsy cases and identified mixed cell follicles by the immunohistochemical method. We examined the number and size of the mixed cell follicles, and the ratio of each component cell of these follicles, in the anterior pituitary at various age groups. The number of follicles increased with age, and the size of the follicles also tended to enlarge with age. Statistical analysis showed that a high correlation existed between age and the number or the size of the mixed cell-follicles formed by various adenohypophyseal cells. In addition, when the proportions of the different cell types that formed the follicles were examined, sex differences were observed with aging for the GH cells, the PRL cells, and the gonadotroph (GTH) cells, while no changes were observed with aging in both men and women for the ACTH cells and TSH cells. These results indicate that the number, size, and ratio of each component cell of follicles in the anterior pituitary are adequately applicable for the purpose of age estimation in routine forensic medicine.

The aim of this study was to reveal the clinical features of anterior urethral recurrence in patients with superficial bladder cancer, and to determine the appropriate treatment. Three hundred and three patients with superficial bladder cancer, who were newly diagnosed and initially treated conservatively in our hospital between 1965 and 1990, were followed for at least 5 years and their clinical outcomes were analyzed. Clinical factors, including anterior urethral recurrence, were evaluated statistically regarding tumor progression. Eight patients (2.6%) had anterior urethral recurrence following superficial bladder cancer. Twenty-four patients (7.9%) had tumor progression and 149 (49.2%) had tumor recurrence. In a multivariate analysis using a logistic model, anterior urethral recurrence was the most important factor, followed by histological grade. Four of 5 patients who were treated for anterior urethral recurrent tumors by transurethral resection showed progression and died of the cancer within one year. Two of the remaining three patients who underwent radical cysto-urethrectomy at the time of anterior urethral recurrence survived. Anterior urethral recurrence following superficial bladder cancer is a predictor for rapid subsequent malignant progression. Once there is anterior urethral recurrence, radical intensive therapy, including radical cysto-urethrectomy, should be carried out immediately.

High levels of soluble CD30 (sCD30) were detected in the serum and synovial fluid of patients with rheumatoid arthritis (RA), indicating the involvement of CD30+ T cells in the pathogenesis. We investigated the induction of CD30 and its functions in CD4+T cells from patients with established RA (disease duration >_2 years). CD4+ T cells from both the peripheral blood (PB) and synovial tissue (ST) of RA patients expressed surface CD30 when stimulated with anti-CD3 antibody (Ab) and anti-CD28 Ab, but their CD30 induction was slower and weaker compared with PB CD4+ T cells of healthy controls (HC). Immunohistochemical analysis showed that only a small proportion of lymphocytes expressed CD30 in the ST (-1%). RA PB CD4+ T cells, after recovery from 6-day stimulation with anti-CD3 Ab and anti-CD28 Ab, showed in intracellular cytokine staining that CD30+ T cells could produce more interleukin-4 (IL-4) but less interferon-gamma. In the culture of RA PB CD4+ T Cells with anti-CD3 Ab and anti-CD28 Ab, blocking anti-CD30 Ab similarly inhibited the cell proliferation and activation of nuclear factor-kappaB on day 4 in RA and HC, but inhibited the apoptotic cell death on day 6 only in RA. These results indicate that despite high-level expression of sCD30, the anti-inflammatory activity of IL-4-producing CD30+ CD4+ T cells may be limited in the ST due to a poor induction of surface CD30 and a susceptibility to CD30-mediated cell death.

In patients with hepatocellular carcinoma (HCC), natural killer (NK) cell activity decreases significantly, and the reduced activity may be associated with the progression of HCC. In this study we evaluated the effects of pulsing with interleukin (IL)-2 and/or IL-12 on the activation of freshly isolated peripheral blood lymphocytes (PBL) derived from patients with HCC. PBL obtained from 9 HCC patients, 4 liver cirrhosis patients, and 9 normal subjects were cultured in the presence of IL-2 and/or IL-12. After 24 h of incubation, the levels of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha presented in the supernatants were determined by enzyme-linked immunosorbent assay (ELISA). The IFN-gamma and TNF-alpha production of PBL pulsed by a combination of IL-2 and IL-12 was significantly higher than those of PBL stimulated by either IL-2 or IL-12 alone. The mRNA encoding perforin, granzyme B, as well as IFN-gamma and TNF-alpha, were markedly enhanced in PBL stimulated with a combination of IL-12 and IL-2. The pulsing procedure of IL-12 in combination with IL-2 resulted in the increase of IFN-gamma and TNF-alpha, and the expression of perforin and granzyme B mRNA in PBL obtained from HCC patients, as well as in those obtained from normal subjects. These results indicate that adoptive immunotherapy based on PBL pulsed with a combination of IL-2 and IL-12 may be a promising adjunctive strategy for HCC treatment.

Germline mutations of the LKB1 gene are associated with Peutz-Jeghers syndrome (PJS), which is characterized by mucocutaneous pigmentation and gastrointestinal hamartoma with an increased risk of cancer development. In this study, we have employed polymerase chain reaction and DNA sequencing analysis to characterize the LKB1 gene in a 25-year-old Japanese PJS patient. Direct sequence analyses revealed a novel single base deletion at nucleotide 844 in exon 6 (844delC) in one LKB1 allele, resulting in a frame shift and in the introduction of a premature termination codon in this mutated allele.

We observed the distribution of CD56+ epithelial cells in the pancreatic duct system using 25 fetal, one infantile, 3 normal adult, 4 diabetic, and 8 chronically inflamed pancreatic tissue samples. In the early stage of gestation (12 to 17 weeks), CD56+ cells were commonly seen in the immature tubular structures. They were often continuous to pancreatic islets, and their distribution was similar to that of synaptophysin (Syn)+ cells, suggesting that they are precursors of islet neogenesis. Their number decreased in proportion to gestational age. Instead, from 24 weeks of gestation, luminal cell clusters that were common in interlobular ducts revealed CD56+. These cell clusters were unrelated to islet neogenesis and Syn expression. Similar CD56+ luminal cell clusters were also observed in cases of chronic pancreatitis, whereas they were scarce in normal adult and diabetic tissues. CD56+ cells were also occasionally seen in intralobular ducts, intercalated ducts, and centroacinar cells in cases of chronic pancreatitis. We conclude that there are two types of CD56+ epithelial cells in the pancreatic duct system: CD56+ endocrine cells are numerous during the early stage of gestation, when islet neogenesis appears, while CD56+ luminal cells may represent developmental and regenerative changes of pancreatic ducts.

Ocular manifestations in patients with psoriasis vulgaris have been investigated in only a small number of studies. Our purpose was to identify tear film function and ocular pathologies associated with psoriasis vulgaris in patients who had received neither oral retinoids nor phototherapy. We examined 62 eyes of 31 patients with psoriasis and 60 eyes of 30 age-and-sex matched healthy volunteers. In addition to complete ocular and dermatological examination, tear film function (i.e., tear secretion and tear film stability) were assessed by the Schirmer-I test, as well as by tear film break-up time. None of the controls had any ocular abnormalities, whereas 67.74% of patients with psoriasis had various anterior segment pathologies (P<0.00009). The most prevalent finding was chronic blepharoconjunctivitis (64.5%), as the only pathology (n=9) or in association with other findings, including nonspecific corneal opacities (n=4), cataract (n=3), both corneal opacities and cataract (n=2), and corneal pigment dispersion (n=2). The Schirmer-I test results revealed comparable mean values in the patient group (9.8+-4.2 mm) and in the controls (11.2+-3.7 mm; P=0.078). However, mean tear film break-up time was significantly shorter in the patients (7.2+-2.5 sec) than in the healthy persons (11.7+-3.1 sec; P=0.001). In agreement with some previous reports, our findings clearly demonstrated that early ocular involvement occurs in patients with psoriasis vulgaris, irrespective of the history of previous therapeutic modalities (e.g., retinoid therapy and phototherapy). Thus, the present findings are suggestive of the contributory role of primary etiologic factors of psoriasis in the pathogenesis of ocular changes in patients with psoriasis vulgaris.

This study was designed to explore whether it was possible to evaluate the severity of VSD, PDA, and ASD by measuring brain natriuretic peptide (BNP) levels. We also investigated normal BNP levels in children to provide a baseline for our study. We measured BNP levels in 253 normal children, including 11 normal neonates, and in 91 VSD patients, 29 PDA patients, and 34 ASD patients. BNP levels showed no age-related differences in normal children (the mean value: 5.3 +/- 3.8 pg/ml). In the healthy neonates, BNP levels rose from 10.4 +/- 11.9 pg/ml in cord blood to 118.8 +/- 83.2 pg/ml on day 0, then fell to 15.3 +/- 7.8 pg/ml by day 7. In VSD and PDA patients, BNP levels correlated significantly with Qp/Qs, LVEDV, and peak RVP/LVP. In ASD patients, BNP levels correlated with Qp/Qs and RVEDV. Especially, in VSD patients, as an index corresponding to 1.5-2.0 of the Qp/Qs ratio, BNP levels of 20-35 pg/ml were found to be best with regard to both sensitivity and specificity. In the healthy neonates, BNP levels changed rapidly after birth. In VSD, PDA, and ASD patients, BNP levels were well-correlated with the severity of the disease. Especially, in VSD patients, it that appears BNP levels may be useful in evaluating surgical indications, with 20-35 pg/ml levels being the appropriate cut-off value.

Chemical shift MRI is widely used for identifying adenomas, but it is not a perfect method. We determined whether combined dynamic MRI methods can lead to improved diagnostic accuracy. Fifty-seven adrenal masses were examined by chemical shift and dynamic MR imaging using 2 MR systems. The masses included 38 adenomas and 19 non-adenomas. In chemical shift MRI studies, the signal intensity index (SI) was calculated, and the lesions classified into 5 types in the dynamic MRI studies. Of the 38 adenomas studied, 37 had an SI greater than 0. In the dynamic MRI, 34 of 38 adenomas showed a benign pattern (type 1). If the SI for the adenomas in the chemical shift MRI was considered to be greater than 0, the positive predictive value was 0.9, and the negative predictive value was 0.94 and kappa = 0.79. If type 1 was considered to indicate adenomas in the dynamic MRI, the corresponding values were 0.94, 0.81 and kappa = 0.77 respectively. The results obtained when the 2 methods were combined were 1, 0.95 and kappa = 0.96 respectively. The chemical shift MRI was found to be useful for identifying adenomas in most cases. If the adrenal mass had a low SI (0 < SI < 5), dynamic MRI was also found to be helpful for making a differential diagnosis.

The purpose of this study was to compare the MR characteristics of renal cell carcinomas against histologic findings and to assess the correlations among signal intensity, tumor enhancement, and pathologic findings. Fifty-four patients (56 lesions) were examined by MR imaging and then underwent partial or radical nephrectomy. The pathologic diagnosis of all lesions was renal cell carcinoma. All MR examinations were performed as dynamic studies using the same 1.5-T scanner. MR characteristics were compared against pathologic findings after resection, and the correlations among signal intensity, tumor enhancement, and pathologic findings were then assessed. A significant correlation was observed between tumor grade and tumor enhancement, with G3 lesions tending to show little enhancement. Regardless of the histologic classification, G3 tumors were found to contain highly heterotypic cancer cells and very few vessels by histopathologic examination. No significant correlations were noted between the other MR characteristics and pathologic findings. Renal cell carcinomas showing little enhancement tend to be highly malignant lesions based on the pathologic findings. Special consideration is required for these tumors with regard to the selection of surgical intervention and follow-up observation.

We studied the association of gamma-glutamyltransferase (GGT) and other serum markers of liver injury with daily alcohol consumption in a healthy population of 1,043 Japanese males. A positive correlation between daily alcohol consumption and biochemical markers, such as log GGT (r = 0.432), log AST (r = 0.244) or log LAP (r = 0.246), was seen in all drinkers. However, there was a negative correlation, such as log GGT (r = -0.434), log AST (r = -0.424) or log LAP (r = -0.430), in heavy drinkers who consumed more than 70 g ethanol a day. On the other hand, a positive correlation, such as log GGT (r = 0.426), log AST (r = 0.247) or log LAP (r = 0.216) was found in moderate drinkers who consumed less than 70 g ethanol a day. Interestingly, there was a tendency toward negative association between alcohol consumption and the Tokyo University ALDH2 Phenotype Screening Test (TAST) score in the heavy drinkers, and there was a tendency toward positive association between GGT and TAST score in this group. Our results suggest that there are 2 groups of drinkers, those with elevated GGT (good responders) and those with normal GGT (poor responders) despite heavy drinking.

We observed a bilateral and symmetrical variation of the anterior belly of the digastric muscle during the dissection of a 35-year-old female cadaver. The accessory muscle bundles were arranged in a cross. These bundles were found superficial to the mylohyoid muscle and deep in the platysma. Such a variation from perfect symmetry has not been previously reported. To avoid misinterpretation of radiological tests, it is important to be aware of bilateral and symmetrical variations of the anterior belly of the digastric muscle when examining the floor of the mouth and the submental region.

The purpose of this study was to elucidate the role of extracellular matrix components such as aggrecan, fibronectin, and laminin in the extraocular muscle of patients with strabismus. Resected tissues of the medial rectus muscle of 47 patients with intermittent exotropia obtained during recession-resection surgery were frozen under liquid nitrogen and pulverized by a Freezer/Mill to solubilize the tissue for enzyme immunoassay. The total amounts of aggrecan, fibronectin, and laminin in the resected tissue were correlated with clinical data of patients such as age, exodeviation, and refractive error. The amount of aggrecan decreased significantly with the advance of age (P < 0.0001, Spearman rank correlation test), while the amount of laminin or fibronectin had no correlation with age. Patients with basic type intermittent exotropia showed larger, although not significantly, amounts of aggrecan than those with convergence insufficiency type (P = 0.0538, Mann-Whitney U-test). The amount of aggrecan may be related to motor aspects of intermittent exotropia.

1) It has been found that the peripheral blood of hybrid adult dogs contains about 29.4 % of lymphocytes in average. When such a blood is passed through the glass wool column the leucocytes containing 68-90 % (81.6% in average) lymphocytes are obtained. 2) In the single culture of such lymphocytes alone and mixed culture both live lymphocytes and sonicated lymphocytes in the presence of 1% (vIv) PHA, the peak of the blastformation of lymphocytes is observed at culture hour 72. 3) In the abscence of PHA both single culture and mixed culture of lymphocytes show hardly any blastformation. 4) In the mixed culture of live lymphocytes with homogenate of sonicated lymphocytes with addition of 1% (vIv) PHA the rate of blast. formation observable at culture hour 72 and the rejection of kidney trans· plant 7 days after its transplantation of hybrid adult dogs show a direct correlation, demonstrating that the mixed lymphocyte reaction reflects accurately the difference in donor histocompatibility antigens against the recipient.

The role of -SH groups in mitochondrial energy transfer reaction was studied by observing the reduction of a disulphide, 5, 5'-dithiobis (2-nitrobenzoic acid), DTNB, a specific analytical agent for the estimation of -SH groups in biological materials, by addition of it to the isolated rat liver mitochondria in various respiratory states, as defined by CHANCE and WILLIAMS. 1. In the various respiratory states, states 1 to 5, the reduction of DTNB proceeds most rapidly at state 5, and most slowly at state 3. DTNB reduction at state 5 is suppressed by the partial oxidation of respiratory carriers with oxygen (state 4) and the addition of respiratory substrate does not affect the DTNB reduction. 2. The retardation in the reduction rate at state 3 is relieved partially by a respiratory inhibitor, KCN, and is intensified markedly by oligomycin, an inhibitor of oxidative phosphorylation. An uncoupler for oxidative phosphorylation, DNP, does not affect the reduction rate at state 3. At state 4 the reduction is stimulated by DNP and KCN, but is unaffected by oligomycin. The results suggest that the alteration in the functions of the energy transfer reaction in mitochondria is accompanied by changes in the occurrence and the functioning of -SH groups which can be detected by the reactivity with DTNB. The data suggest also that there are at least two kinds of -SH groups reacting with DTNB: the one is the -SH group which reacts DTNB actively when the respiratory carriers are kept reduced, and the other is the one which reacts actively when the respiratory carriers are kept oxidized, participating in the phosphorylating system and its reactivity with DTNB diminishes in the actively phosphorylating states (states 2 and 3).

With the purpose to clarified the mode of localization and mechanisms of activation of ATPase in the mitochondrial membrane, analyses were made on the properties of mitochondrial ATPase from the structural and functional aspects. The activation of ATPase by DNP and Mg++ and the oligomycin sensitivity were investigated in a series of inner membrane fragment samples obtained by ultrasonic irradiation and those samples obtained in the processes of isolation and purification of ATPase from rat liver mitochondria and beef heart mitochondria in parallel with electron microscope observations. As a result it has been found that the membrane fragments obtained from rat liver and beef heart mitochondria by ultrasonication exhibited high respiratory activity and unmasked ATPase activity which was charac· terized by remarkable stimulation by Mg++ and inhibition by oligomycin and azide. Therefore, mitochondrial ATPase seems to be bound fairly closely to the inner mitochondrial membrane. In the membrane fragments prepared by ultrasonication of intact mitochondria, ATPase activity was stimulated by DNP, but in the supernatant fractions was not. On the other hand, the supernatant fraction obtained from BHM and inner membrane fragments by severe sonication exhibits a marked ATPase activity and the activity incresed in each step of the purification on the treatments with acid, protamine and heat. Especially in the case of membrane fragments the protamine treatment can be omitted. Electron microscope observation of the fractions in each step of the purification proved the head pieces to be ATPase. The ATPase activity of solubilized head pieces is insensitive to oligo. mycin and coincides with the soluble ATPase of PULLMAN etat. (8) in the points of its cold labile property and optimum pH, but it shown no accele. ration of ATPase activity by DNP.

For the purpose to obtain the information of the mechanism of protein uptake by the tumor cells, some cytochemical and electron microscopic observations were carried out on Ehrlich ascites tumor cells incubated with horseradish peroxidase (basic hemoprotein, molecular weight approximately 40,000) in vitro. In the earlier periods of the incubation peroxidase was found to be adsorbed on some area of surface of the tumor cells forming a thin protein layer, where an active pseudopodia formation was observed. With the lapse of time, the protein was taken in the deep cytoplasm by the infoldings of the cell membrane and accumulated in the cytoplasmic vesicles having limiting membrane. Concerning the accumulation of the protein into the vesicles, small tubular structures in the cytoplasm connecting the cell surface and the vesicles, were considered to participate in the intracellular transportation of peroxidase taken up. In cold environment (2°C), the formation of pseudopodia and deep inward infoldings of the cell membrane was inhibited and simultaneously the uptake of peroxidase stopped. Iodoacetate and sodium fluoride also effected to suppress the pseudopodia and infoldings formation moderetely, as well as uptake of peroxidase, though they did not stop completely. These facts have indicated that horseradish peroxdase is taken up by Ehrlich ascites tuimor cells through pinocytosis which involves energy-requiring process dependent upon glycolytic metabolism of the tumor cells.

For the purpose to reveal the changes in the metabolism of erythroblast in varied specialization stages the author observed the Feulgen DNA level of rabbit erythroblasts by microspectrophotometry. Observations were made on normal and anemic animals, and those receiving a mass red cell transfusion at the recovery stage of anemia where the early denucleation is stimulated. Observations have revealed that in normal erythropoiesis the DNA contents are kept at n to 2 n level from the proerythroblast to late basophilic stage, but in later stages, polychromatic and orthochromatic, DNA level per cell decreases gradually with advance of the cell specialization reaching the minimum level, nearly haploid level, at orthochromatic stage where most cells are believed to be denucleated. In blood depleted animals nearly the same pattern of DNA level was observed in connection with erythroid specialization as that in normal animal, except a relatively high DNA level in the later specialization. In the cases of the hemolytic anemia a similar tendency has been observed but the minimum level of DNA remains at a higher level, hypo-diploid level, in poly- and orthochromatic stages. Twenty-four hours after the mass red cell transfusion by which severe anemia has been recovered to the original level within one hour, the pattern of the DNA level of the erythroblast returns to the normal one showing a very low DNA level at the polyand the orthochromatic stages. The data indicate that the DNA synthesis of erythroblast kept at n to 2 n levels until the late basophilic stage begins to decline at polychromatic stage and reaches nearly haploid level at orthochromatic stage, but in active hemopoiesis the DNA synthesis is stimulated and the DNA contents are kept at a high level even in the late specialization stages, showing no relation between the denucleation and the low DNA level.