Reduced expression and aberrant localization of p120catenin in human squamous cell carcinoma of the skin

BACKGROUND: p120catenin (p120ctn), a member of the Armadillo protein family, is ubiquitously expressed and binds to classical cadherins together with other catenins to participate in the adherens junction. p120ctn has numerous isoforms generated through extensive splicing and alternative usage of translation initiation codons. Although the involvement of p120ctn in cell growth control has been postulated, little has so far been known about its expression patterns in the skin and epidermal tumors. OBJECTIVE: To identify the isoforms expressed in benign and malignant keratinocytes and to analyze the expression patterns of p120ctn in epidermal tumor specimens. METHODS: HaCaT, DJM-1, BSCC-93, HSC-1, HSC-5 and A431 cells along with normal skin tissue were subjected to RT-PCR to identify the expressed isoforms. For immunofluorescence study, surgical specimens including 29 squamous cell carcinomas (SSCs), 4 basal cell carcinomas (BCCs) and 4 seborrheic keratoses as well as 3 normal skin samples were stained with specific antibodies to detect p120ctn and E-cadherin. RESULTS: RT-PCR revealed that the isoform 3A was predominantly expressed with faint expression of the isoform 4 and that there was no difference in expressed isoforms between the examined cell lines. Immunofluorescent staining indicated that the expression of p120ctn was significantly reduced in all of the examined squamous cell carcinomas and that p120ctn was frequently localized in cytoplasm. In benign tumors and normal samples, p120ctn was properly expressed in cell-cell boundaries. Furthermore, there were several SCCs where E-cadherin continued to be expressed with no expression of p120ctn. CONCLUSION: Reduced expression and aberrant localization of p120ctn are among the most common events during the development and/or progression of SCCs.     

Cellular immune responses to feline immunodeficiency virus (FIV) induced by dual-subtype FIV vaccine

Vaccine-induced T cell responses to FIV were assessed by measuring FIV-specific cytokine and cytotoxic-effector molecule production. A total of 22 cats at 10-12 weeks of age received either dual-subtype FIV vaccine (n=12), uninfected cell lysate (n=5) consisting of cells used to produce vaccine viruses, or no immunization (n=5). Significant increases in mRNA and protein production of T-helper 1 (Th1) cytokines (IL-2, IFNgamma), mRNA production of a cytotoxic-effector molecule (perforin), and lymphoproliferation response were observed in peripheral blood mononuclear cells (PBMC) from dual-subtype FIV-vaccinated cats after in vitro stimulation with inactivated FIV. In contrast, no statistically significant increase in FIV-stimulated mRNA production of Th2 cytokines (IL-4, IL-6) or other cytotoxic-effector molecules (TNFalpha, FasL) was observed in the PBMC from dual-subtype vaccinated cats. Moreover, no FIV-specific increases in the IFNgamma, IL-2, and perforin mRNA productions and in the IFNgamma bioactivity and lymphoproliferation responses were observed in the PBMC from cell-immunized cats. These observations suggest that IFNgamma induction, lymphoproliferation, and significant portion of IL-2 and perforin productions in the PBMC from dual-subtype vaccinated cats are clearly specific for viral antigens. Overall, dual-subtype FIV vaccine elicited strong Th1 response (IFN(, IL-2), which may contribute to the vaccine protection by enhancing the perforin-mediated cytotoxic-cell activity against FIV.     

Angiotensinogen gene variation and renoprotective efficacy of renin-angiotensin system blockade in IgA nephropathy

BACKGROUND: Blockade of the renin-angiotensin system (RAS) is well documented to be renoprotective; however, not all patients with glomerulonephritis respond well to this therapy. The interindividual variation in response to the RAS blockade may be in part genetically determined, whereas the results have been controversial. METHODS: We investigated whether the therapeutic efficacy of angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin receptor blocker on renal prognosis is modified by the angiotensinogen gene (AGT) polymorphism in immunoglobulin A nephropathy (IgAN). In total, 259 patients with histologically proven IgAN were analyzed for clinical manifestations, renal survival, and their associations with AGT A(-20)C and M235T. RESULTS: The renal prognosis of 110 patients, who received ACE inhibitors/angiotensin receptor blocker during their clinical course, was significantly better than those without ACE inhibitors/angiotensin receptor blockers despite higher blood pressures and heavier proteinuria. The Cox proportional hazards regression model showed an increased hazard ratio (HR) for urinary protein (more than 1.0 g/day) of 3.346 (P = 0.0001), hypertension of 1.949 (P = 0.01), deteriorated renal function of 3.040 (P < 0.0001), no ACE inhibitor/angiotensin receptor blocker administration of 2.725 (P = 0.0004), and the T235 and C(-20) haplotype of 1.608 (P = 0.0322). Only in patients carrying at least one M235 and A(-20) haplotype did the administration of ACE inhibitors/angiotensin receptor blockers have no significant effect on the prognosis of renal function (Kaplan-Meier, log rank test, chi2 = 0.700; P = 0.4028), whereas it was significant in patients who had other haplotypes of AGT (chi2 = 11.805; P = 0.0006). CONCLUSION: This study provides evidence that the M235T and A(-20)C genotype of AGT can influence the therapeutic efficacy of a RAS blockade on the renal survival in IgAN.     

Short-term postoperative flow changes after free radial forearm flap transfer: possible cause of vascular occlusion

The risk for free flap thrombosis is greatly influenced by blood flow. Postoperative hemodynamic changes in vascular pedicles of the microvascular skin flap have not been reported, however. This study focuses on the intraoperative and postoperative changes in the flow volume in the vascular pedicles of the free forearm flap examined by color Doppler ultrasonography. The arterial flow volume increased continuously until day 7, compared with which, the volume after flap elevation was 36%. On day 1, it reached only 52%. In the venous pedicle, the flow volume through the cutaneous vein was only 37% compared with that through the radial vena comitans after flap elevation, whereas the volume through both veins was equal on day 7. Drastic changes in the flow explain the possible vascular occlusion during the early postoperative period in the free forearm flap transfer.     

Delayed radiation necrosis with extensive brain edema after gamma knife radiosurgery for multiple cerebral cavernous malformations--case report

A 39-year-old man presented with multiple intracranial cavernous malformations manifesting as intractable seizures persisting for more than 20 years. He underwent gamma knife radiosurgery (GKRS) for right frontal and left temporal cavernous malformations. He began to suffer from progressive left hemiparesis and inattention 2 years 5 months after the GKRS. Magnetic resonance imaging showed abnormal ring enhancement and extensive brain edema around the right frontal lesion. Conservative therapies such as external decompression, low-dose barbiturates, and mild hypothermia had no effect on his clinical status. Stereotactic biopsy of the ring-enhanced area demonstrated gliosis. Signs of cerebral herniation appeared, so we performed partial resection of the right frontal lobe. His symptoms recovered immediately. Subsequent hyperbaric oxygen (HBO) therapy significantly improved the extensive brain edema. Delayed radiation necrosis associated with potentially fatal brain edema may occur after GKRS for cavernous malformations. Internal decompression and subsequent HBO therapy were very effective for the treatment of these lesions.     

Effects of particulate matter on daily mortality in 13 Japanese cities

BACKGROUND: In recent years, numerous reports demonstrating the relationship between an increase in the concentration of fine particulate matter (PM2.5) and daily mortality have been released in the United States and Europe. There have been few studies that clearly characterize the short-term effects of particulate matter on the mortality in Japan. We conducted data analysis to investigate the short-term effects of suspended particulate matter (SPM) on mortality in Japan. METHODS: In this study, we used data sets from the 13 largest cities containing data on the daily mortality of residents aged 65 years or older, concentrations of air pollutants including SPM, temperature, and humidity. Risk ratios for mortality resulting from respiratory diseases, cardiovascular diseases, and all causes other than accidents, from 1990 through 1994, were summarized using a generalized additive model (GAM) and a meta-analysis of random effect model. RESULTS: The risk ratios for an increase of 10 microg/m3 in SPM concentrations adjusted for SO2, NO2, CO, Ox, temperature, and humidity were 1.0077 for all causes of mortality, 1.0109 for respiratory diseases, and 1.0091 for cardiovascular diseases, and the lower limits of the 95% confidence intervals for the risk ratios were greater than one for all cases. With regards to the effects of time lag, risk ratios were higher for the SPM concentrations on the day when the mortality was recorded, and the preceding day. CONCLUSIONS: These results suggest a positive relationship between SPM concentrations and daily mortality in Japan.     

Genetic polymorphisms of alcohol and aldehyde dehydrogenases and risk for esophageal and head and neck cancers

Alcoholic beverages are causally related to cancer of the oral cavity, pharynx, larynx and esophagus. Ethanol is oxidized to acetaldehyde and then to acetate by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), both of which have genetic polymorphisms. A review of case-control studies of the effects of ALDH2, ADH2 and ADH3 genotypes shows consistently positive associations between inactive heterozygous ALDH2 and the less-active ADH2 genotypes and the risk for esophageal cancer in East Asian heavy drinkers and this enzyme-related vulnerability may extend to light-to-moderate drinkers. Some studies suggest similar associations with the risk for head and neck cancer in moderate-to-heavy-drinking Japanese. An established carcinogen in experimental animals, acetaldehyde can interact with human DNA. ALDH2-associated cancer susceptibility fits into a scenario in which acetaldehyde plays a critical role in the development of human cancer. Alcohol flushing and drinking behavior may partly explain this carcinogenic effect in carriers of less-active ADH2 genotypes. Whether the ADH3 genotype influences head and neck cancer risk in Western nations is controversial. Professional and public education about risky conditions connected to the ALDH2 and ADH2 genotypes and environmental factors is important in a new strategic approach to the prevention of alcohol-related cancers in East Asians. The use of simple tests to identify inactive ALDH2 on the basis of alcohol flushing responses could benefit many people, by helping them to identify their own cancer risks. Such testing could also help clinicians diagnose esophageal cancer earlier, through the use of endoscopic screening in the high-risk population.     

Connexin26-mediated gap junctional communication reverses the malignant phenotype of MCF-7 breast cancer cells

A growing body of evidence indicates that the gap junction (GJ) plays a pivotal role in tumor suppression by exerting cell-cell communication. It has, however, been reported that expression of connexin26 (Cx26) protein is induced in human ductal carcinomas of the breast and that its amount increases in proportion to the grade of malignancy. We thus examined the effects of over-expressed Cx26 on growth characteristics in GJ-deficient human MCF-7 breast cancer cells that maintain the phenotype of early-stage cancers. MCF-7 cells were transfected with Cx26 cDNA, and several clones of stable transformants exhibiting a high level of cell-cell communication were established. When they were examined in terms of various growth characteristics in vitro , the proliferation rate and the saturation density were drastically reduced in Cx26-transfected clones compared with the mock-transfectant. The anchorage-independent growth capacity was also decreased by 50–75% after transfection of Cx26. Furthermore, the cell migration toward growth factors and cell invasion into Matrigel in a Boyden chamber were suppressed to 5–10% and 20–60%, respectively, of the control in Cx26-transfected clones. When implanted into the mammary fat pads of nude mice in the presence of an excess of 17β-estradiol, Cx26-transfected clones tended to show slower tumor growth than the mock-transfectant, although the difference was not statistically significant. Our results strongly suggest that the induction of Cx26 protein observed in human breast cancers, reported previously, may not be very relevant to the development of breast cancers, and that Cx26 can function as a tumor suppressor in breast cancer cells.     

Steroid injection for Reinke's edema using fiberoptic laryngeal surgery

OBJECTIVE: Since 1990, we have performed steroid injections into the vocal fold under topical anesthesia using fiberoptic laryngeal surgery (FLS) in an outpatient clinic. The aim of this study was to retrospectively assess the usefulness of this treatment method in 44 patients with mild Reinke's edema. MATERIAL AND METHODS: Using fiberoptic monitoring of the larynx, a curved injection needle was inserted via the oral cavity and triamcinolone acetonide was injected into Reinke's space of the bilateral vocal fold. RESULTS: Remission or improvement was observed in almost all patients in terms of both patients' self-rating of hoarseness and endoscopic vocal fold findings The maximum phonation time was a mean of 9.0 s before operation and 11.4 safter operation, and this increase was significant (p < 0.01). Voice pitch also improved, from 168 to 181 Hz, in female patients, and this increase was also significant (p < 0.05). CONCLUSION: Steroid injection is considered to be useful for treating mild Reinke's edema.     

Recurrent laryngeal nerve regeneration by tissue engineering

The recurrent laryngeal nerve (RLN) does not regenerate well after it has been cut, and no current surgical methods achieve functional regeneration. Here, we evaluate the functional regeneration of the RLN after reconstruction using a biodegradable nerve conduit or an autologous nerve graft. The nerve conduit was made of a polyglycolic acid (PGA) tube coated with collagen. A 10-mm gap in the resected nerve was bridged by a PGA tube in 6 adult beagle dogs (group 1) and by an autologous nerve graft in 3 dogs (group 2). Fiberscopic observation revealed functional regeneration of the RLN in 4 of the 6 dogs in group 1. No regeneration of the RLN was observed in any dog in group 2. We also tested for axonal transport, and measured the compound muscle action potential. The RLN can be functionally regenerated with a PGA tube, which may act as a scaffold for the growth of regenerating axons.