PTEN loss in intraductal carcinoma of the prostate has low incidence in Japanese patients

Clinical and genomic features of prostate cancer (PCa) vary considerably between Asian and Western populations. PTEN loss is the most frequent abnormality in intraductal carcinoma of the prostate (IDC-P) in Western populations. However, its prevalence and significance in Asian populations have not yet been well studied. In the present study, we evaluated PTEN expression in IDC-P in a Japanese population and its association with ERG expression. This study included 45 and 59 patients with PCa with and without IDC-P, respectively, who underwent radical prostatectomy. PTEN loss was observed in 10 patients with PCa with IDC-P (22%) and nine patients with PCa without IDC-P (17%). ERG expression was relatively frequent in patients with PCa with PTEN loss, although a significant difference was not observed. The co-occurrence of PTEN loss and ERG expression was observed in four patients with PCa with IDC-P and one without IDC-P. PTEN loss and ERG expression did not affect progression-free survival, regardless of the presence of IDC-P. The frequency of PTEN loss in IDC-P is lower in Asian patients than in Western patients. Our results indicate that mechanisms underlying IDC-P in Asian populations are different from those of Western populations.     

Comparison of the axonal and glial reactions between the caudal and rostral border in the cryoinjured dorsal funiculus of the rat spinal cord

Axonal and glial reactions to traumatic injury were compared between the caudal and rostral border of the lesion after freeze-injury to the C3 dorsal funiculus by attaching a liquid nitrogen-cooled copper probe to the dorsum of the rat spinal cord. The axonal and glial changes were examined up to 60 days postoperative by light and electron microscopy and immunohistochemistry for neurofilaments. Regenerative axonal changes and the appearance of numerous undifferentiated cells were found at the caudal border 7 days after cryoinjury. In contrast, such axonal and cellular reactions were scarce at the rostral border. Undifferentiated cells clearly manifested their phenotypes by differentiating into oligodendrocytes or astrocytes 11 days postinjury. The results indicated that glial cell reactions occurred in association with regenerative axonal changes at the proximal stump of the injured nerve fibers, suggesting that regenerating and demyelinated naked axons could be responsible for the appearance of the immature glial cells.     

Clinical studies on 9, 3"-diacetylmidecamycin in respiratory tract infections in the field of pediatrics (author's transl)

Laboratory and clinical studies were performed on 9, 3"-diacetylmidecamycin (MOM), a new macrolide antibiotic in the field of pediatrics, and the results were as follows. Antibacterial activity: For 32 clinically isolated strains of Staphylococcus aureus, the MIC of MOM ranged from 0.78 to 1.56 micrograms/ml for 17 of the 32 strains, and exceeded 100 micrograms/ml for the 15 remaining strains with both inoculum sizes of 10(8) cells/ml and 10(6) cells/ml. For 27 strains of Streptococcus pyogenes, the MIC range was wide, varying from 0.10 to greater than or equal to 100 micrograms/ml and less than 1.56 micrograms/ml for about 2/3 of all the 27 strains. For 9 strains of Bordetella pertussis, the MIC ranged from 0.10 to 0.78 microgram/ml and 0.10 to 0.39 microgram/ml with the inoculum size of 10(8) cells/ml and 10(6) cells/ml, respectively. Comparing the antibacterial activity of MOM with that of midecamycin (MDM) and erythromycin (EM) against these 3 bacterial species, MOM was almost comparable to MDM, but about 2 or 3 tubes inferior to EM. Absorption and excretion: MOM was administered to 5 children (from 5 to 8 years old) at a dose of 10 mg/kg or 20 mg/kg at 30 minutes before breakfast. The peak of serum concentration was observed 30 minutes to 1 hour after administrations of both dosages: 0.52 to 1.71 micrograms/ml with 10 mg/kg and 0.88 to 1.77 micrograms/ml with 20 mg/kg. 0.09 to 1.10% and 0.94 to 1.19% of MOM were excreted in the urine within the first 6 hours, respectively. Clinical results: MOM was administered to 28 pediatric patients with acute respiratory tract infections (acute pharyngitis; 2, acute purulent tonsillitis; 19, acute bronchitis; 4, acute pneumonia; 2 and whooping cough; 1). The overall clinical response was excellent in 10, good in 10, fair in 3 and poor in 5; the efficacy rate was 71.4%. Isolated S. pyogenes strains were eradicated in 6 out of 11 strains, reduced in 3 and unchanged in 2 strains. One strain of S. aureus was eradicated. One strain of non group A beta-Streptococcus was reduced. Haemophilus influenzae strains were reduced in 1 of the 4 strains and unchanged in 3 strains. The overall eradication rate was 41.2%. No side effects or abnormal laboratory findings were observed, but 1 case complained of a bitter taste.     

Accumulation of class I mutant p53 and apoptosis induced by carboplatin in a human glioma cell line

Following DNA damage, wild-type p53 increases and mediates the multiple cellular responses for the repair of DNA damage or apoptosis. Inactivation of p53 by single-amino-acid substitutions contributes to the malignant phenotype and confers resistance to therapy. Among tumor-derived p53 mutants, class I mutants still retain a native-like three-dimensional structure, whereas class II mutants have unfolded DNA-binding domains. Sequencing analysis demonstrated that a human glioma cell line (U-373MG) had only a class I mutant form of p53 of His273, which targets an Arg273 that contacts DNA but retains the native structure. In this study, we investigated the metabolic alteration of the class I mutant p53 in apoptosis of U-373MG. The cell cycle progression of U-373MG cells was affected by the addition of carboplatin, while the amount of mutant p53 also increased in their nuclei. The treated cells underwent apoptosis 48h after exposure to 50 μg/ml carboplatin. Although the exact mechanism of the class I mutant p53 in the process of apoptosis has not yet been clarified, the fact that accumulation of the activated mutant p53 in the nucleus of U-373MG is concomitant with apoptosis, just as wild-type p53 does, implies that the class I mutant p53 might retain the ability to participate in apoptosis.     

Localization of l-afadin at puncta adhaerentia-like junctions between the mossy fiber terminals and the dendritic trunks of pyramidal cells in the adult mouse hippocampus

We have recently found a novel cell-cell adhesion system at cadherin-based adherens junctions. This system consists of at least two components: nectin, an immunoglobulin-like cell adhesion molecule with Ca(2+)-independent homophilic binding activity, and l-afadin, an actin filament-binding protein that connects nectin to the actin cytoskeleton. In the present study, we investigated immunocytochemically the localization of l-afadin in the mouse hippocampus. At the light microscopic level, l-afadin immunoreactivity was demonstrated as flattened disks in the stratum lucidum of the CA3 area. By immunoelectron microscopy, signals for l-afadin were highly concentrated in a symmetrical manner at the puncta adhaerentia-like junctions between the mossy fiber terminals and the dendritic trunks of pyramidal cells. We furthermore immunostained the hippocampus with antibodies recognizing both l-afadin and s-afadin, a small splicing variant of l-afadin that is identical to AF-6. Immunoreactivity for l- and s-afadins was demonstrated not only as the flattened disks similar to that for l-afadin, but also as numerous fine dots widely distributed in all synaptic layers of the CA1 and CA3 areas. The latter finding may correspond with the recent report by Buchert et al. (1999, J. Cell. Biol. 144:361-371), who found that s-afadin (AF-6) and/or l-afadin was localized at the postsynaptic membranes of asymmetric synaptic junctions. Our present results indicate that l- and s-afadins are differentially distributed in the hippocampus and suggest that l-afadin localized at the puncta adhaerentia-like junctions in the mossy fiber terminals may regulate the structural and functional organization of these complex synaptic structures.     

A case of left renal cell carcinoma in a young male adult with left varicocele

A 25-year-old man presented to our hospital with the chief complaint of left-sided painless scrotal swelling. Varicocele was diagnosed and high ligation was performed. Two months later, he noticed asymptomatic gross hematuria. Transabdominal ultrasonography and abdominal computed tomographic scanning showed a left renal tumor measuring more than 10 cm in diameter. Radical nephrectomy (thoraco-abdominal approach) was performed and pathological diagnosis was granular cell carcinoma (G2, pT2, INF alpha, pNX, pMX). He then received intramuscular injections of interferon-alpha 3 million units on three days per week. The frequency of renal cell carcinoma was reported to be about 1-3% for individuals in the 20s in the recent Japanese literature, and renal cell carcinoma in a young man with left varicocele is very rare.     

A case of primary small cell neuroendocrine carcinoma of the uterus

Neuroendocrine carcinoma of the uterine endometrium is extremely rare and found in <1% of all primary endometrial carcinomas. We report a case of neuroendocrine carcinoma of the endometrium detected in a 65-year-old woman and focus our attention on the main imaging features. The low apparent diffusion coefficient value and high maximum standardized uptake value for neuroendocrine cancer serve to distinguish this cancer from endometrial cancer.     

Combining the Tumor Contact Length and Apparent Diffusion Coefficient Better Predicts Extraprostatic Extension of Prostate Cancer with Capsular Abutment: A 3 Tesla MR Imaging Study

Purpose: To assess the diagnostic performance of the tumor contact length (TCL) and apparent diffusion coefficient (ADC) for predicting extraprostatic extension (EPE) of prostate cancer with capsular abutment (CA).Methods: Ninety-three patients with biopsy-proven prostate cancer underwent 3-Tesla MRI, including diffusion-weighted imaging (b value = 0, 2000 s/mm²) and radical prostatectomy. Two experienced radiologists, blinded to the clinicopathological data, retrospectively assessed the presence of CA on T2-weighted imaging (T2WI). TCL on T2WI and ADC values were measured on detecting CA in prostate cancer. We used the receiver operating characteristic curves to assess the diagnostic performance of TCL and ADC values for predicting EPE.Results: CA was present in 58 prostate cancers among 93 patients. The cut-off value for TCL was 6.9 mm, which yielded an area under the curve (AUC) of 0.75. This corresponded to a sensitivity, specificity, and accuracy of 84.2%, 61.5%, and 69.0%, respectively. The cut-off value for ADC was 0.63 × 10^–3 mm²/s, which yielded an AUC of 0.76. This, in turn, corresponded to a sensitivity, specificity, and accuracy of 84.2%, 59.0%, and 67.2%, respectively. The combined cut-off value of TCL and ADC yielded an AUC of 0.82. The specificity (84.6%) and accuracy (81.0%) of the combined value were superior to their individual values (P < 0.05).Conclusion: A combination of TCL and ADC values provided high specificity and accuracy for detecting EPE of prostatic cancer with CA.