Ultrastructural alteration of cartilaginous fibril arrangement in the rat mandibular condyle as revealed by high-resolution scanning electron microscopy.

Three-dimensional alteration of fibrillar matrix in the rat mandibular condylar cartilage was investigated with a high-resolution scanning electron microscope (SEM) and it was determined whether alterations correlate with developing occlusion and advancing age. Two important SEM techniques of DMSO freeze-cracking and treatment with trypsin and hyaluronidase were employed to remove interfibrillar proteoglycans and disclose fibril arrangement. Our SEM investigation demonstrated that collagen fibrils in the fibrous zone covering hyaline-cartilaginous area in the condyle are thicker (50 to 80 nm in diameter) than the fibrils (30 to 50 nm in diameter) that predominantly constituted an interterritorial fibrillar matrix (IFM) in the area. While the thick fibrils had a distinct striation of about 55 nm periodicity, the thin fibrils had no distinguishable striation. The thick fibrils having a periodic striation of about 60 nm was found along with the thin fibrils, also in the IFM in the aged rats and in the deep IFM, but were considerably less than the thin fibrils. The fibrils in the fibrous zone and IFM were disorderly arranged at 19-day-insemination age. In 1-week-old rats whose incisors erupted, the fibrils constituting the fibrous zone altered from disordered to ordered arrangement. The IFM in these rats took the form of a network. Incorporation of small fibrillar bundles into the fibrillar network was seen in 2-week-old rats whose upper and lower first molars erupted. In 8-week-old rats whose molars had erupted completely, the IFM completely occupied by regularly oriented fibrils appeared additionally.(ABSTRACT TRUNCATED AT 250 WORDS)     

Malignant phyllodes tumor of the prostate: retrospective review of specimens obtained by sequential transurethral resection

A case of malignant phyllodes tumor of the prostate in a 67-year-old man is reported. The patient was referred to a hospital for urinary retention. From material taken at three transurethral resections of the prostate (TURP), a histological diagnosis of benign prostatic hyperplasia was made. However, at the fourth TURP, phyllodes tumor was diagnosed due to the presence of elongated epithelial ducts and proliferating cellular stroma with mitosis and nuclear atypia. Two months later, total cystoprostatectomy was performed. Histologically, the tumor was composed of dysplastic stromal cells and irregularly elongated epithelial ducts. Five months later the patient developed multiple lung and pelvic lymph node metastases and died. This report documents progression to a higher histological grade of prostatic phyllodes tumor documented with sequential pathological findings obtained from four TURP and surgical specimens over about 3 years.     

Heterogeneity of Igh-linked allotypic determinants expressed on functional T cell subsets as detected by monoclonal antibodies

Hybridomas producing monoclonal antibodies (mAb) specific for immunoglobulin heavy chain (Igh) allotype-linked gene products expressed only on functional T cells but not on B cells and macrophages were established by fusion of allotype congenic SJL (Igh-1^b) and SJA/9 (Igh-1^a) B cells immunized reciprocally with partner spleen cells with a myeloma P3-X63-Ag8-653 of BALB/c origin. Nine mAb have been selected on the criteria that they can specifically block various antigen-dependent functions of known T cell subsets in in vitro immune responses of mouse strains having the corresponding Igh allotype, but not the other one. These included (a) four mAb that augment the in vitro secondary antibody response of either Igh-1^a or Igh-1^b strains and thus are considered to react with the Igh-linked allotypic determinant expressed on suppressor T cells, (b) one mAb that inhibits the helper T cell activity of Igh-1^b but not of Igh-1^a strains, (c) two mAb that inhibit the antigen-induced pro-liferative response of Igh-1^a but not Igh-1^b strains, and (d) two mAb that block the cytotoxicity of alloreactive cytotoxic T cells of Igh-1^a strains. The linkage to Igh-1 allotype of the T cell products was established by testing with Igh-1-congenic strains with different backgrounds including the H-2 complex. Some of the mAb were able to react with cloned hybridomas and a continuous cell line of the given allotype and functions. Each mAb was able to block one of the known functions of T cell subsets, but not others, indicating the existence of the heterogeneity and multiplicity of the Igh allotype-linked products on T cells.     

Contribution of gene products encoded within the unique short segment of equine herpesvirus 1 to virulence in a murine model

The pathogenesis of three equine herpesvirus 1 (EHV-1) recombinants was assessed in a CBA mouse model. Sequences encoding the majority of glycoproteins I (gI) and E (gE) were deleted from the pathogenic EHV-1 strain RacL11 (L11ΔgIΔgE), and sequences comprising the 3859 bp deletion within the strain KyA U_S segment, which includes genes 73 (gI), 74 (gE), and 75 (putative 10 kDa protein 75), were re-inserted into attenuated KyA (KgI/gE/75). In addition, genes gE and 75 were inserted into KyA to generate the EHV-1 recombinant KgE/75. The insertion of the 3859 bp U_S segment was sufficient to confer virulence to KyA, as indicated by pronounced signs of clinical disease including substantial weight loss. A large plaque morphology was observed in cells infected with KgI/gE/75 compared with KyA, and a small plaque phenotype was observed in cells infected with L11ΔgIΔgE compared with RacL11. These data indicate that gI and/or gI and gE contribute to the ability of EHV-1 to spread directly from cell-to-cell. The deletion of both gI and gE from the pathogenic RacL11 strain did not reduce clinical signs of disease in infected mice, but did decrease mortality compared with RacL11. Furthermore, the insertion of genes 74 (gE) and 75 into the vaccine strain KyA did not alter the attenuated phenotype of this virus. Finally, KgI/gE/75 and RacL11 elicited the production of the proinflammatory chemokines MIP-1, MIP-1β, and MIP-2 in the lungs of infected mice, while KyA did not, suggesting that gI and/or gI and gE contribute to the up-regulation of these mediators of inflammation. These findings show that gI, and/or gI and gE restore a virulent phenotype to the EHV-1 KyA strain, and indicate that virulence factors, in addition to gI and gE, contribute to the pathogenesis of the RacL11 strain.     

Strenuous exercise-induced change in redox state of human serum albumin during intensive kendo training

A high-performance liquid chromatographic (HPLC) analysis of human serum albumin (HSA) using an ion-exchange (DEAE-form) column shows three components: The principal component corresponds to human mercaptalbumin (HMA); the secondary to nonmercaptalbumin (HNA), having mixed disulfide with cystine (HNA[Cys]), or oxidized glutathione (HNA[Glut]); and the tertiary to HNA, oxidized more highly than mixed disulfide. The purpose of the present study is to clarify the effects of strenuous exercise load on HMA--><--HNA conversion (i.e., dynamic change in redox state) of HSA from elite kendo athletes (n=30; 20.0+/-1.1 years old). They participated in an intensive kendo training camp for 5 d. The mean value for the HMA fraction (f[HMA]) of kendo athletes after camp (62.8+/-2.4%) was significantly lower than before camp (71.9+/-3.7%) (p<0.0005). In contrast, the mean value for f(HNA-1) (i.e., f[HNA(Cys) and HNA(Glut)]) after camp (34.2+/-2.1%) was significantly higher than before camp (25.7+/-3.7%) (p<0.0005). These results suggested that strenuous physical exercise markedly increased the oxidized albumin level in extracellular fluids during the intensive training camp.     

Clinicopathological and molecular characteristics of gastric papillary adenocarcinoma

Papillary adenocarcinoma is defined as carcinoma with a well-defined papillary or villous structure. Despite sharing clinicopathological and morphological features with tubular adenocarcinomas, papillary adenocarcinomas frequently show microsatellite instability. The present study aimed to clarify the clinicopathological features, molecular classification, and programmed death-ligand 1 (PD-L1) expression characteristics of papillary adenocarcinoma, especially tumors with microsatellite instability. We examined the microsatellite status and expression of mucin core proteins and PD-L1 as well as the clinicopathological features in 40 gastric papillary adenocarcinomas. Surrogate immunohistochemical analysis of p53 and mismatch repair proteins along with Epstein-Barr virus-encoded RNA in situ hybridization were performed for molecular classification. Female predominance and frequent microsatellite instability were observed in papillary adenocarcinoma in comparison with tubular adenocarcinoma. The presence of microsatellite instability in papillary adenocarcinoma was significantly correlated with older age, tumor-infiltrating lymphocytes, and Crohn's-like lymphoid reactions. Surrogate examination demonstrated that the genomically stable type (17 cases, 42.5%) was the most common, followed by the microsatellite-unstable type (14 cases, 35%). Among the seven cases showing PD-L1-positive expression in tumor cells, four involved carcinomas with microsatellite instability. These results reveal the clinicopathological and molecular characteristics of gastric papillary adenocarcinoma.     

Caf versus caf plus medroxyprogesterone acetate for treatment of liver metastases of breast cancer

A controlled randomized trial was conducted to compare the effectiveness of a CAF therapy including cyclophosphamide (CPA), adriamycin (ADR) and 5-fluor-ouracil (5FU) with that of CAF plus medroxyprogesterone acetate (MPA) therapy including CPA, ADR and 5FU plus MPA for the treatment of liver metastases from breast cancer. A total of 34 patients with unresectable liver metastases from breast cancer were divided into two treatment groups (CAF and CAF + MPA) with stratification for estrogen receptor status. The response rate was 13% (2 PR in 16 patients) for CAF therapy and 22% (1 CR and 3 PR in 18 patients) for CAF plus MPA therapy. There was no significant difference in response rates, median survival periods and survival rates between the two treatment groups. However, CAF therapy had significantly more toxicity than did CAF plus MPA therapy. The findings of this study suggested that CAF plus MPA therapy is a well-tolerated and effective treatment for patients with liver metastases of breast cancer.