A prognostic immune predictor,HLA-DRA,plays diverse roles in non-muscle invasive and muscle invasive bladder cancer

BackgroundThere is an increasing demand for prognostic immune biomarkers of cancer. The prognostic significance of immune markers has been shown for various cancers, but biomarkers of bladder cancer (BCa) have not been fully evaluated. To clarify the role of human leukocyte antigen DR alpha chain (HLA-DRA) in BCa development, we examined expression of HLA-DRA mRNA in tissue samples of non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC).Materials and MethodsTissues of 96 NMIBC, 43 MIBC and 59 controls comprising noncancerous BCa surrounding tissues were used to examine the expression of HLA-DRA gene by real-time polymerase chain reaction. The expression of up-stream genes regulating HLA-DRA were also measured to explain the role of HLA-DRA in BCa.ResultsPatients with high grade NMIBC showed higher expression of HLA-DRA than those with low grade NMIBC (P < 0.05). In addition, NMIBC patients who progressed to MIBC showed high expression of HLA-DRA mRNA. Kaplan-Meier analysis showed that NMIBC patients with low expression of HLA-DRA had better progression-free survival than those with high expression (P = 0.004). Moreover, the expression of genes regulating HLA-DRA varied in NMIBC and MIBC, indicating a different immunoregulation effect of HLA-DRA in both cancers.ConclusionsHigh expression of HLA-DRA in NMIBC patients has implications for patient stratification strategies, as well as for BCa tumor immunology.     

Osteoconduction at porous hydroxyapatite with various pore configurations

To assess the histological response and the reinforcing effects of bone ingrowth within porous hydroxyapatite (HA) implants depending on pore geometry, four kinds of cylindrical-type with parallel linear pores phi50, 100, 300, 500 microm), one kind of sponge-type with irregular interconnecting pores (phi250 microm) and one cross-type with crossing linear pores (phi100 x 120 microm) of porous HA were prepared. Eighty-four rabbits were divided into six groups, and a 5 x 5 x 7 mm sized porous HA block was inserted through the medial cortical window of the proximal tibia. Histomorphological changes were examined using light and scanning electron microscopy. A biomechanical compression test was performed using material test machines. After implantation, the implants showed different histological changes depending on pore geometry. Active osteoconduction was also found in the phi50 microm sized cylindrical-type porous HA. Evidence of remodeling of new bone and bone marrow formation within porous HA was found in the larger cylindrical-types (phi300, 500 microm), and the sponge- and cross-types. The biomechanical test showed that the ultimate compressive strength increased significantly in the phi300 microm sized cylindrical-type, and in the sponge- and cross-types eight weeks after implantation. Porous HA with cylindrical pores could be a useful graft material due to its strength, osteoconductivity and the ease with which its pore geometry can be controlled.     

A case of leukemia-associated arthritis--identification of leukemic cells in synovial fluid by light microscopy

One case of arthritis complicating leukemia is described in which leukemic cells were identified in synovial fluid by light microscopy. Although arthritis is a well-known manifestation of leukemia with an incidence of 13.5%, the pathogenesis often is unclear, and the direct demonstration of leukemic cells in synovial fluid has been very uncommon. A 16 year-old male patient was admitted due to left elbow joint pain and swelling. Synovial fluid examination revealed blast cells and this finding has directed to a final diagnosis of acute lymphoblastic leukemia.     

Optic disc and early glaucomatous visual field loss

In the early stages of glaucoma, the disc changes prior to visual field loss, so assessment of the optic disc is very important for the evaluation of the glaucoma patient. The aim of this study is to assess the glaucomatous disc and to look for the features of the optic disc that are commonly associated with early visual field loss. Forty-three eyes of 28 patients were included in this investigation. The criteria for inclusion were a cup/disc(C/D) ratio of more than 0.4 by direct ophthalmoscopy, no visual field defect with Goldmann perimetry, and open anterior chamber angle. Each optic disc was photographed with a Canon fundus camera with Polaroid 600 Plus film. Each photographic set was then examined stereoscopically for morphologic parameters: 1) comparison of vertical versus horizontal C/D ratio; 2) presence of nasal cupping; 3) presence of overpassing vessels; 4) presence of baring of circumlinear vessels; 5) presence of peripapillary atrophy; 6) ratio of the thinnest neuroretinal rim(NRR) width in the vertical sectors of the NRR width of the temporal sector. All subject's central visual fields were examined with an automated static perimeter, Humphrey program C30-2 with STATPAC. The C/D ratio estimated by direct ophthalmoscopy consistently showed a smaller C/D ratio than that found by the stereophotographic method. The parameter with the highest probability value to differentiate between the optic disc of the early visual field loss and the optic disc of normal subjects was "Ratio of the thinnest NRR width in the vertical sectors to the NRR width of the temporal sector less than or equal to 85%". Although it has less resolving power than slide film, a stereo disc photograph with Polaroid film is a quick and simple method of recording changes, and the ratio of the thinnest NRR width in the vertical sectors to the temporal sector is a good predictive parameter for detection of early visual field loss.     

Pathogenesis and prevention of stomach cancer.

In many Western developed countries, the incidence of stomach cancer has declined dramatically. This decrease was an extraordinary, "unplanned triumph", especially when compared to other cancers. Stomach cancer is still the most prevalent malignant tumor in Korea. Most Koreans carry Helicobacter pylori in their stomach. Thus, a new hypothesis, based on the relationship between the host and Helicobacter pylori, is presented as the carcinogenesis of human stomach cancer. The reasons for why the N-nitrosamide hypothesis should be dismissed as the etiology of stomach cancer, and why the contemporarily available principles and practice of intervention strategies to rapidly decrease the surprisingly high prevalence rate of Helicobacter pylori infection are impractical at this moment, are explained. In order to introduce an alternative provisional strategy of the "planned triumph" for the population vulnerable to stomach cancer, vitamin C is defined as an anti-inflammatory agent on the basis of the pathogenesis of Helicobacter pylori infection.     

Sexual activities and attitudes of adolescent Koreans

Data regarding the sexual behaviors of 849 Korean adolescents ( years) were collected. Behaviors reported for males vs. females were 36.5 vs. 27.0% for kissing, 27.2 vs. 14.8% for petting, and 22.9 vs. 9.8% for coitus. In addition to reporting a greater number of experiences, males reported a greater number of partners for all three behavior categories. Among those who participated in coitus, nearly one third of the males and two thirds of the females reported only one partner. Two thirds of the males considered their recent experiences with coitus to be satisfactory, whereas over half of the females gave a neutral response. About 37% of males and 55% of females reported that their most recent coital experience was less than a month ago. On average, the coitally active adolescents began sexual activity at about 18 years of age. Interpretations of these data must take into consideration the respondents' hesitancy in the Korean setting to admit to having sexual experiences. Because premarital sex for adolescents is considered very undesirable in the Korean social setting, the respondents' reporting bias might be in the direction of underreporting. Findings are discussed in the context of unplanned pregnancy and abortion. This investigation was supported by the Special Programme of Research, Development and Research Training in Human Reproduction, World Health Organization, Project No. 91207 BSDA.     

Tissue engineered artificial skin composed of dermis and epidermis

Abstract: We made an artificial skin comprised of a stratified layer of keratinocytes and a dermal matrix with a type I collagen containing fibroblasts. In this work, we showed keratinocyte behavior under primary culture, gel contractions varying with concentration of collagen solution, and cell growth plots in the collagen gel. The optimum behavior of dermal equivalent could be obtained using 3.0 mg/ml collagen solution and attached gel culture. The attached gel culture had a jumping effect of growth factor on cell growth at the lag phase. To develop the artificial skin, 1× 10⁵ cells/cm² of keratinocytes were cultured on the dermal equivalent at air-liquid interface. Finally, to overcome the problem that artificial skin of collagen gel was torn easily during suturing of grafting, we prepared histocompatible collagen mesh and attached the mesh to the bottom of the gel. Cultured artificial skins were successfully grafted onto rats.     

Non-invasive detection of fecal protein kinase C betaII and zeta messenger RNA: putative biomarkers for colon cancer

We have developed a non-invasive method utilizing feces, containing sloughed colonocytes, as a sensitive technique for detecting diagnostic colonic biomarkers. In this study, we used the rat colon carcinogenesis model to determine if changes in fecal protein kinase C (PKC) expression have predictive value in monitoring the neoplastic process. Weanling rats were injected with saline or azoxymethane (AOM) and 36 weeks later fecal samples and mucosa were collected, poly A+ RNA isolated, and quantitative RT-PCR performed using primers to PKC betaII and zeta. Fecal PKC betaII and zeta mRNA levels were altered by the presence of a tumor, with tumor-bearing animals having a 3-fold higher (P < 0.05) PKC betaII expression as compared with animals without tumors. In addition, AOM-injection increased mucosal PKC betaII mRNA expression compared with saline controls. No effect of tumor incidence on mucosal PKC betaII expression was observed. In contrast, fecal PKC zeta expression was 2.5-fold lower (P < 0.05) in animals injected with azoxymethane versus saline. Since tumor incidence exerts a reciprocal effect on fecal PKC betaII and zeta mRNA expression, data were also expressed as the ratio between PKC betaII and zeta. The isozyme ratio was strongly related to tumor incidence, i.e. ratio for animals with tumors was 2.18 +/- 1.25, animals without tumors was 0.50 +/- 0.16, P = 0.025. We demonstrate that the expression of fecal PKC betaII and zeta may serve as a noninvasive marker for development of colon tumors. A sensitive technique for the detection of colon cancer is of importance since early diagnosis can substantially reduce mortality.      

Target-dependent axonal sprouting following vagal-hypoglossal nerve anastomosis in cats

Purpose: To investigate the relationships between the axonal sprouting and target neurotization by central neurons after nerve heterocon-nection. Methods: Unilateral (right) vagal-hypoglossal nerve anastomosis (VHA) was performed in adult cats. Following 3-315 days postoperation (dpo), quantitative analyses and ultrastructural changes in the proximal portion of the vagal-hypoglossal heteroconnected nerve as well as the time course of neuronal regeneration were studied. Along with this, horseradish peroxidase (HRP) retrograde tracing technique was used to label the neurons of dorsal motor vagal nucleus (DMV) and nucleus ambiguus (NA) to ascertain if target neurotization was established. Results: The contralateral (left) intact vagus nerve proximal to the level of ansa cervicalis showed an average of 33 +/- 1 myelinated and 74 +/- 4 unmyelinated axons in 727 &mgr;m(2) sectional area of the nerve. In the heteroconnected nerve at the corresponding level just proximal to the anastomosis site, there was a marked increase in the number of small axons sprouting from the unmyelinated nerve fibers between 18 and 25 dpo. The number of these axonal sprouts appeared to decline at 32 dpo but its increase of 131 % was sustained until the late regeneration stage at 315 dpo when compared with the contralateral nerve serving as a control. The mean number of myelinated axons per area unit (727 &mgr;m(2)) was reduced to 18 at 3 dpo but was immediately restored to the normal range at 7 dpo. The retrograde labelling of neurons in both the DMV and NA was first detected at 22 dpo and was progressively increased peaking by about 67 dpo. Conclusions: We conclude that compared with the unmyelinated axons, the myelinated axons may acquire a superior interaction with the new target. Furthermore, the postoperative neurotization of tongue muscles may initiate and facilitate the retraction of the redundant axonal sprouts.     

Amphiphilic amino acid copolymers as stabilizers for the preparation of nanocrystal dispersion

The recent advance of particle size engineering in nanometer ranges has widened the formulation opportunities of relatively water-insoluble drugs. However, the ‘nanoformulation’ suffers from a lack of systematic understanding about the requirements of polymeric stabilizers. Furthermore, the polymers that can be used for the preparation of nanocrystals are so limited that finding a proper stabilizer for a given formulation is often difficult. In this study, amino acid copolymers whose properties can systematically be tailored are developed, and their morphological and compositional effects are investigated. Copolymers containing lysine (K) as their hydrophilic segments, and phenylalanine (F) or leucine (L) as their hydrophobic segments successfully produce stable nanocrystals (200–300 nm) in water, while copolymers of K and alanine (A) could not generate nanosized particles. Not the morphology but the hydrophobicity of copolymers seems to be a critical parameter in the preparation of drug nanocrystals by wet comminution. The effective stabilization performance of copolymers requires the hydrophobic moiety content to be higher than 15 mol%. Comminution for only 5 min is long enough for nanocrystal preparation, and the crystallinity of drug is found intact after the processing.