The combination of oral-recombinant methioninase and azacitidine arrests a chemotherapy-resistant osteosarcoma patient-derived orthotopic xenograft mouse model

Cancer Chemotherapy and Pharmacology - Cancers are methionine (MET) and methylation addicted, causing them to be highly sensitive to MET restriction. The present study determined the efficacy of...     

Extracellular matrix remodeling in oral submucous fibrosis: its stage-specific modes revealed by immunohistochemistry and in situ hybridization

BACKGROUND: Oral submucous fibrosis (OSF) is a chewing habit-related pre-cancerous condition of the oral mucosa affecting predominantly south Asians. It is histopathologically characterized by epithelial atrophy and fibrosis of the subepithelial connective tissue. Fibrosis extends all the way into the muscle layer, leading to difficulty in mouth opening. However, the dynamics of extracellular matrix (ECM) remodeling with OSF progression is largely unknown. METHODS: Forty biopsy specimens of OSF and 10 of normal buccal mucosa were examined for expression/deposition modes of eight ECM molecules by histochemistry, immunohistochemistry, and in situ hybridization. RESULTS: In the early stage of OSF, tenascin, perlecan, fibronectin, collagen type III were characteristically enhanced in the lamina propria and the submucosal layer. In the intermediate stage, the ECM molecules mentioned above and elastin were extensively and irregularly deposited around muscle fibers. In the advanced stage, such ECM depositions decreased and were entirely replaced with collagen type I only. Their gene expression levels varied with progression of fibrosis, but the mRNA signals were confirmed in fibroblasts in the submucosal fibrotic areas. CONCLUSIONS: The results indicate that the ECM remodeling steps in OSF are similar to each phase of usual granulation tissue formation. Restricted mouth opening may be a result of loss of variety of ECM molecules including elastin into the homogeneity of collagen type I replacing muscle fibers.     

An elderly case of idiopathic retroperitoneal fibrosis]

An elderly case of idiopathic retroperitoneal fibrosis (IRPF) with bilateral ureteral obstruction was reported. A 74-year-old man was admitted with complaints of general fatigue and loss of appetite. An elastic hard mass with a smooth surface was palpated in the left upper quadrant of the abdomen. Abnormal ESR and CRP were noticed. Abdominal ultrasonography showed both a homoechoic mass which surrounded the aorta in the retroperitoneal space and bilateral hydronephrosis. Computed tomography revealed a retroperitoneal mass involving bilateral ureters. Magnetic resonance imaging demonstrated a mass with a sharp image and signal intensity. Furthermore the morphological relationship between the mass and the ureters and major vessels clearly indicated the characteristics of benign retroperitoneal fibrosis. Based upon the above findings, a diagnosis of IRPF was made. After confirming the histological diagnosis by biopsy, treatment consisting of bilateral ureterolysis, intra-abdominal transposition of ureters and oral administration of prednisolone was performed, resulting in a normalization of laboratory findings. Analysis of 86 previously cases of IRPF reported up to 1990 in Japan, revealed the peak age to be in the 7th decade with predominance in males (males: females = 57:29).     

Direct detection of Molluscum contagiosum virus in clinical specimens by in situ hybridization using biotinylated probe.

Molluscum contagiosum virus (MCV) is an unclassified poxvirus which has recently become recognized as causing a major sexually transmitted disease. At present no assay is available for specific detection of MCV because the virus cannot be serially propagated in cell culture. Since MCV produces an abortive, limited growth with some cytopathic effect in certain cell lines, we were able to develop an in situ hybridization assay for detection of MCV genome in clinical specimens. Human fetal diploid lung cell monolayers were infected with clinical specimens, and after proper incubation and fixation in paraformaldehyde, hybridization was performed under full stringency conditions with a molecularly cloned biotinylated probe. Only MCV infected cells showed homology to the MCV probe with a purple-brown cytoplasmic staining. Additionally, we have described an in situ hybridization assay for direct detection of MCV genome in formalin-fixed, paraffin-embedded biopsies. Characteristic intracytoplasmic Molluscum bodies (Henderson-Paterson bodies) were detected in stratum spinosum cells of the epidermis. Striking staining similarities have been observed between in situ hybridization and haematoxylin-eosin cytostaining. These procedures are the first successful identification of MCV genome in clinical samples by molecular hybridization, with sensitivity and specificity equal to or greater than electron microscopy.     

Canine Latissimus Dorsi Muscle: An Apparatus for Isometric Force Measurements

Abstract: This paper describes a device used to measure the isometric forces generated during electrical stimulation of the canine latissimus dorsi muscle in vivo with a preserved neurovascular supply. This device uses 2 strain gauge force sensors linked to a movable alignment frame to which the muscle is attached. The muscle length is controlled by the application of known weights to the system. The device has a frequency of response of 17.5 Hz and compliance of -0.1 mm N^-1, and its experimental performance was tested in the anesthetized mongrel dog.     

Prognosis for patients with carcinoma in the middle third of the stomach

In 268 of the 1,115 patients (24.0%) with gastric cancer who underwent a curative resection in our clinics, the tumor was located in the middle third of the stomach. The clinicopathological features and prognosis of these patients were divided into two groups, according to site of the tumor: anterior wall (n = 58) vs. other sites (n = 210). Clinicopathological factors did not differ between the two groups. The survival time for patients with a tumor in the anterior group was shorter than that for patients with a tumor in other areas (P < 0.05). The five-year survival rate was 79.3% for patients with an anterior tumor and 91.9% for those with a tumor at a different site. A multivariate analysis indicated lymph node metastasis, serosal invasion, and anterior wall location to be independent prognostic factors indicative of a poor prognosis when the tumor was located in the middle third of the stomach. For such patients, close follow-up is needed to detect possible recurrences. © 1993 Wiley-Liss, Inc.     

Unilateral sudden deafness as a primary symptom of brainstem and cerebellar infarction]

We report a case with a unilateral sudden sensorineural hearing loss caused by an infarction of brainstem and cerebellum. The patient was a 74-year-old male presented with a sudden onset of hearing loss and tinnitus in the right ear and dizziness. Steroid was administered on suspicion of idiopathic sudden deafness. However, the initial symptoms were deteriorated approximately 2 weeks later. He newly complained of the numbness of the right face and double vision, and he was transferred to our hospital for further evaluation. Neurological examination demonstrated horizontal nystagmus, diminution in the right facial sensation, right peripheral facial palsy, right hearing loss and cerebellar ataxia. Urgent MRI disclosed fresh infarctions of the right middle cerebellar peduncle and cerebellum localized in the territory of anterior inferior cerebellar artery. In general, idiopathic sudden deafness and Meniere's disease are frequent diagnosis in cases of sudden hearing loss with vertigo, but these symptoms may rarely be caused by cerebrovascular disorder. In patients with risk factors for arteriosclerosis, cerebrovascular disorder should be taken into consideration even if idiopathic sudden deafness may be suspected clinically. We emphasize the diagnostic importance of careful observation on neurological findings and early detection of radiological abnormalities on MRI.     

Rheumatic heart disease: proinflammatory cytokines play a role in the progression and maintenance of valvular lesions

Heart lesions of rheumatic heart disease (RHD) patients contain T-cell clones that recognize heart proteins and streptococcal M peptides. To functionally characterize heart-infiltrating T lymphocytes, we evaluated their cytokine profile, both directly in situ and in T-cell lines derived from the heart (HIL). Interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, and IL-10 expressions were characterized in 20 heart tissue infiltrates from 14 RHD patients by immunohistochemistry. IFN-gamma-, TNF-alpha-, and IL-10-positive cells were consistently predominant, whereas IL-4 was scarce in the valves. In agreement with these data, the in vitro experiments, in which 13 HILs derived from heart samples of eight patients were stimulated with M5 protein and the immunodominant M5 (81-96) peptide, IL-4 was detected in HIL derived from the atrium (three of six) but not from the valve (zero of seven). IFN-gamma and IL-10 production were detected in culture supernatants in 11 of 13 and 6 of 12 HILs, respectively. The predominant IFN-gamma and TNF-alpha expression in the heart suggests that Th1-type cytokines could mediate RHD. Unlike in reversible myocardium inflammation, the significantly lower IL-4 expression in the valvular tissue (P = 0.02) may contribute to the progression of the RHD leading to permanent valvular damage (relative risk, 4.3; odds ratio, 15.8). The lack of IL-4 in vitro production by valve-derived HIL also emphasizes the more severe tissue destruction in valves observed in RHD.     

Clinicopathologic differences between 22 cases of CD56-negative and CD56-positive subcutaneous panniculitis-like lymphoma in Japan

CD56 is an important marker for prospecting clinicopathologic features of cytotoxic T-cell and natural killer (NK)/T-cell lymphomas. We examined 22 cases of subcutaneous panniculitis-like lymphoma and classified these into CD56-positive and CD56-negative groups. The 11 CD56-negative cases were mainly in the younger age group and had systemic subcutaneous nodules without ulceration. They exhibited subcutaneous invasion by medium-sized lymphoma cells, scattered erythrophagocytosis, patchy necrosis, and little tumor invasion in the superficial dermis. Their lymphoma cells had characteristics of CD3 epsilon-, CD8-, TcR beta F1-, T-cell intracellular antigen (TIA)1-, and granenzyme B-positive cytotoxic T cells and were negative for apoptosis-promoting proteins CD95 (Fas), Bax, CPP32 (caspase 3), and p53 (DO7). Ten patients were alive despite clinical signs of hemophagocytic syndrome and relapses in 7 cases. The 11 CD56-positive cases had systemic ulcerative skin tumors composed of pleomorphic lymphoma cells with massive necrosis and little erythrophagocytosis involving the subcutis and also often the whole dermis. Their tumor cells were positive for CD3 epsilon, TIA1, granenzyme B, CD95, CD95L (Fas ligand), Bax, and CPP32. Three cases were of the TcR beta F1-positive phenotype, 1 was of the TcR gamma/delta-positive T-cell phenotype, and 6 were of the TcR beta F1- and TcR gamma/delta-negative NK/T-cell phenotype. Six cases were p53 (DO7) positive. Seven cases had complications of liver dysfunction and cytopenia, and 8 died of disease. One CD56-negative case and 3 CD56-positive cases had nuclear signals of Epstein-Barr virus-encoded RNA in their lymphoma cells. The 2 groups had significantly (P <0.01) different prognoses by Kaplan-Meier and log-rank methods. Patients with CD56-negative and CD56-positive groups had statistically different clinicopathologic, immunohistologic, and functional findings and prognoses.