Okayama University Medical School

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.

Despite the current diagnostic and serologic testing for SLE, the interval between the onset of symptoms and the diagnosis is still long. In this study, we aimed to show the interval between the initial symptoms and the diagnosis of SLE and to investigate the presence of any relationship between the interval and the initial symptoms. One hundred and thirty-six patients were diagnosed with SLE using the 1982 ARA criteria. The mean age of the patients at diagnosis was 29.9 +/- 10.5 years. The mean interval between the onset of symptoms and the diagnosis of SLE was 21.82 +/- 30.32 months. The subjects were evaluated twice, at intervals of < or = 3 and < or = 12 months after the onset of symptoms. Although arthritis and/or arthralgia were the most common initial symptoms (60.3%), only 26.8% of the patients with these symptoms were diagnosed earlier than 3 months after the onset. If the first initial symptoms were butterfly rash or pericarditis, pleuritis, spontaneous abortion or cognitive dysfunction, they led to early diagnosis. In conclusion, since arthritis and/or arthralgia are the most common initial symptoms of the disease, every young woman with these symptoms should be carefully evaluated for SLE.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Allele and genotype frequencies for 15 short tandem repeat (STR) polymorphisms--D3S1358, TH01, D21S11, D18S51, Penta E, D5S818, D13S317, D7S820, D16S539, CSF1PO, Penta D, vWA, D8S1179, TPOX and FGA--in a Japanese population were estimated. No deviations of the observed allele frequency from Hardy-Weinberg equilibrium expectations were found for any of the systems studied. Between 2 new pentanucleotide STR loci, Penta E and Penta D, for which there is only limited data regarding the allelic distribution in Japanese, the Penta E locus was found to be highly polymorphic and exhibited a tri- or tetra-modal distribution pattern having allelic peaks with 5, 11, 15 and 20 repeats. The distribution was significantly different from that of the other ethnic groups. Statistical parameters of forensic importance, the power of discrimination (PD), observed and expected heterozygosity values (H), polymorphism information content (PIC), power of discrimination (PD), matching probability (pM), power of exclusion (PE), and typical paternity index (PI), were calculated for the loci. These parameters indicated the usefulness of the loci in forensic personal identification and paternity testing among Japanese. The systems Penta E, FGA, D18S51 and D8S1179 were the most informative. This method was successfully applied to forensic personal identification and paternity testing among Japanese, thereby confirming its efficacy for forensic practice.

The aim of the present study was to evaluate the effects of three different anti-androgenic drug-therapy regimens, Diane 35 (cyproterone acetate (CPA) [2 mg] and ethinyl estradiol [35 microg]) plus CPA, Diane 35 plus spironolactone, and spironolactone alone, in patients with hirsutism. In this prospective, randomized clinical study, 79 subjects with idiopathic hirsutismus were studied. The patients were divided into 3 groups. Group I patients (n=32) were treated with Diane 35 plus CPA, group II patients (n=25) with Diane 35 plus spironolactone [100 mg], and group III patients (n=22) with spironolactone [100 mg] alone. Serum FSH, LH, testosterone (T), and DHEAS levels were analyzed before and after treatment at 6 and 12 months. Hirsutism scores were graded according to the Ferriman-Gallwey scoring system, and side effects were monitored. All treatment regimens were found to be efficient and well-tolerated, and none of the patients stopped therapy due to any adverse event. However, in hormone screening, only patients on the Diane 35 plus CPA regimen revealed a decrease in serum T levels after therapy. As such, treatment of each hirsute patient should be planned individually, but with regard to both cost-efficiency and potential side effects, we recommend spironolactone alone in the treatment of hirsutismus.

Several procedures for evaluating fetal well-being are in clinical use. The cardiotocograph is mostly used as a non-invasive procedure to measure fetal well-being in clinical settings. The cardiotocograph displays the fetal heartbeat counts that vibrate. This variation has been classified into 2 categories. We investigated this variation by a novel method, in which we analyzed the change of structure of the attractors in the phase spaces according to the time course. We adopted the global spectrum, which means the distribution of fractal dimensions, for that structure. In this procedure, we discovered a new variation in which the cycle is much longer than the 2 types of known variabilities. Although loud noises such as white noises with a magnitude 1/4 times as large as the standard deviation of the original data were added to the original data, the variations were still detected. The variation is very difficult to detect by Fourier or wavelet transformation, however, because it changes very slowly. Through this new way of analyzing the vibration phenomena, we obtained a new perspective on the biological information available.

This study was conducted to determine the gestational age-related reference range of the preload index [peak velocity during atrial contraction (A)/peak velocity during ventricular systole (S)] for the inferior vena cava (IVC), the right hepatic vein, the middle hepatic vein and the left hepatic vein. The slope and the intercept of the regression line for each preload index were compared among the 4 veins using analysis of covariance. Doppler measurements were obtained for the 4 veins of 316 normal fetuses at 22-40 weeks of gestation. A and S values were measured from the recorded flow velocity waveform of each vein and the A/S ratio was calculated as the preload index. The regression lines for the preload index of the 4 veins decreased gradually throughout gestation. Analysis of covariance revealed no significant differences in the slopes of the regression lines for the 4 veins. However, the intercepts of the regression lines for all hepatic veins were significantly higher than that of the regression line for the IVC (P<0.0001), with the difference ranging from 0.024 to 0.033. There were no significant differences among the intercepts of the regression lines for different hepatic veins. We concluded that the relationship between the preload index and the duration of gestation was statistically similar for all hepatic veins, and strongly resembled that for the IVC.

Administration of phenylhydrazine to rabbits resulted in the denaturation of hemoglobins in erythrocytes, causing the formation of intracellular precipitates known as Heinz bodies, severe hemolytic anemia, and reticulocytosis. To elucidate the molecular mechanism of the destabilization, we allowed human oxyhemoglobins to react aerobically with phenylhydrazine. After treatment with acetic acid/HCl and H2SO4/methanol, the chloroform extract contained blue-green pigments of major products accompanied by different minor products. Each product was isolated by column chromatography. By fast-atom-bombardment mass spectrometry (FAB-MS) and proton nuclear magnetic resonance (1H-NMR) spectrometry, dimethyl esters of N-phenylprotoporphyrin IX and meso, N-diphenylprotoporphyrin IX were determined. Other major products also were determined to be dimethyl esters of triphenyl-and tetraphenyl-substituted protoporphyrins by FAB-MS. The formation of meso, N-diphenylprotoporphyrin indicated that the addition of a phenyl radical to the meso-carbon atom of the protoporphyrin ring occurred. Triphenyl and tetraphenyl adducts also indicated the formation of phenyl radicals in the aerobic reaction of phenylhydrazine with oxyhemoglobins. From these results, we suggest that the formation of phenyl radicals and the replacement of heme with phenyl-substituted protoporphyrins cause the destabilization of hemoglobins to induce Heinz bodies and hemolytic anemia with phenylhydrazine.

Photoelectric dyes absorb light and convert photon energy to electric potentials. To test whether these dyes could be used for retinal prostheses, a simple in vitro screening system was developed. Retinal neurons were cultured from the eyes of chick embryos at the 10-day embryonic stage, at which time no retinal photoreceptor cells have yet developed. Intracellular calcium elevation was observed with Fluo-4 in cultured retinal neurons before and after photoelectric dye was applied at varying concentrations to the culture medium. Five of 7 photoelectric dyes tested in this in vitro system induced intracellular calcium elevation in cultured chick retinal neurons. The intracellular calcium elevation generated by the 5 photoelectric dyes was blocked by extracellular calcium depletion in the case of all 5 dyes, and, except for one dye, by the presence of voltage-gated calcium channel blockers. The photoelectric dyes absorbed light under an inverted microscope and stimulated retinal neurons. This simple in vitro system allows the screening of photoelectric dyes which can be used for retinal prostheses.

To improve the efficacy of interferon (IFN) treatment for chronic hepatitis C, we have proposed the twice-daily administration of IFN-beta as a promising induction therapy. In this study, we demonstrated differences between the clearance of circulating HCV-RNA and the induction of anti-viral actions during the first 2 weeks of treatment. Nine patients with a high viral load and genotype 1b were randomly assigned to 3 groups: group A received 3MU of IFN-beta twice a day at intervals of 5 and 19 h; group B received 3MU of IFN-beta twice a day at intervals of 10 and 14 h; group C received 6MU of IFN-alpha once a day with ribavirin. The expression of OAS2, PKR, and MxA in peripheral blood mononuclear cells (PBMCs) were quantified by real-time polymerase chain reaction method. The viral clearance showed a bi-phasic pattern, and those in the second phase of groups A and B were significantly steeper than that of group C. The peak level of OAS2 during the first phase was correlated with the first phase decay. The MxA expression tended to be higher in group A and B than in group C. The expression of these 3 proteins tended to decrease at day 6 in group C, but increase in groups A and B. These might make differences in the viral decay during the second phase

Anthrax is essentially a disease of grazing herbivorous animals. The most common form of the disease is cutaneous anthrax, which accounts for 95% of all cases. We report here 39 cutaneous anthrax cases in humans that were seen in Eastern Anatolia over a six-year period. The clinical presentation was malignant edema in 16 of the cases (41%) and malignant pustule in 23 (59%). A secondary bacterial infection was present in 13 patients (33.3%) in the vicinity of the lesions. The agent was observed using Gram-stained smears in 25 patients (64%), and Bacillus anthracis was isolated from 15 patients (38.5%). All of the patients were treated with penicillin G or penicillin procaine, except one patient who had a penicillin allergy. One patient with cervical edema (2.5%) died as a result of laryngeal edema and sepsis syndrome. In conclusion, we found that the appearance of the skin lesion of cutaneous anthrax may vary, and this fact, combined with the rarity of this disease, which contributes to a general lack of experience among medical personnel, may make diagnosis difficult in nonagricultural settings