Bone strength of the proximal femur in healthy subjects with ossification of the posterior longitudinal ligament.

We compared the bone strength measured via quantitative computed tomography-based finite element method (QCT/FEM) between healthy adults with and without ossification of the posterior longitudinal ligament (OPLL). No statistically significant difference was observed in the bone strength between healthy adults with and without OPLL. Hyperostosis of the posterior longitudinal ligament in OPLL may not be associated with the systemic bone strength. INTRODUCTION: Although patients with OPLL have been reportedly associated with increased level of bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA), little is known about the bone strength in OPLL subjects. The aim of this study is to investigate the bone strength measured via QCT/FEM in healthy subjects with OPLL using the medical check-up data, including whole-body CT scans. METHODS: We examined 796 participants (529 men and 267 women) who underwent CT scans in a single health center between January 2008 and May 2009. We identified OPLL in whole spine and divided the subjects into two groups: non-OPLL and OPLL groups. We calculated the predicted bone strength (PBS) of the proximal femur using QCT/FEM and examined the bone mineral status of the calcaneus using quantitative ultrasound (QUS). We compared the PBS and the QUS parameters between the non-OPLL and OPLL groups. RESULTS: Seventy-four subjects (9.3%; 57 men and 17 women) were diagnosed with OPLL in the whole spine. The OPLL group was significantly older than the non-OPLL group. No statistically significant difference was observed in the PBS and the QUS parameters between the non-OPLL and OPLL groups in both sexes. Furthermore, no statistically significant difference was noted in the PBS and the QUS parameters between two groups in age- and gender-matched analysis. CONCLUSIONS: Our results suggest that hyperostosis of the posterior longitudinal ligament in OPLL may not be associated with bone strength and bone mineral status at the extremities.

Assessment of the calcification of the nuchal ligament and osteophytes of the cervical spine in obstructive sleep apnoea subjects and snorers.

The previous reports suggest that obstructive sleep apnoea (OSA) is related to metabolic syndrome, mineral metabolism disorders and cardiovascular disease. In addition, a possible relationship between obesity and the calcification of ligaments has been implied. However, the potential link between OSA and the calcification of ligaments has not been directly studied. In this present study, to investigate the potential link between OSA and the calcification of ligaments, we examined the prevalence of the calcification of ligaments in OSA patients and the relationship between these findings and OSA severity. Eighty consecutive patients (60 males, 20 females) diagnosed as OSA or a heavy snorer based on full-night polyso-mnography were retrospectively recruited from May 2006 to July 2008. Each patient underwent cephalometric imaging examination before the arrangement of an oral appliance. One calibrated observer (YS) reviewed the cephalometric images for the presence of calcification of the nuchal ligament and osteophytes of the cervical spine. The prevalence of calcification of the nuchal ligament in OSA patients and snorers was 46.3% (males: 52%, females: 30%) There was a significant positive correlation between the severity of OSA (AHI) and the calcification of the nuchal ligament before and after adjusting for BMI. The prevalence of the calcification of the nuchal ligament in OSA subjects and snorers was higher than in previous studies with non-OSA subjects. In addition, it is suggested that the severity of OSA correlates with the presence of calcification of the nuchal ligament.

Putative classification of clades of enterohemorrhagic Escherichia coli O157 using an IS-printing system.

UNLABELLED: Enterohemorrhagic Escherichia coli O157 (O157) strains can be classified in clades by single nucleotide polymorphisms (SNPs), but this analysis requires significant laboratory effort. As the distribution of insertion sequence (IS) 629 insertions has been reported to be biased among different clades, O157 isolates can be putatively classified in clades by comparison with an IS629 distribution database. A database of the IS629 distribution in O157 strains isolated in Chiba Prefecture and their classification in clades was determined by SNP analysis and IS-printing, an easy and quick analytical tool for IS629 in the O157 genome. The IS629 distribution in O157 strains isolated in Fukuoka and Yamagata Prefectures was determined by IS-printing. These strains were putatively classified in clades by Relative Likelihood calculations that compared the IS-printing data and the IS629 distribution database. Concordance Ratios were calculated, which compared the number of strains putatively classified in a clade by Relative Likelihood to the number of strains classified in that clade by SNP analysis. For the Fukuoka and Yamagata strains, the Concordance Ratios for clades 3, 6 and 8 were 97-100%, for clade 7 about 88%, and for clades 2 and 12 over 90%. In conclusion, O157 clade 2, 3, 6, 7, 8 and 12 strains could be putatively classified by IS-printing. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated that enterohemorrhagic E. coli O157 (O157) strains could be putatively classified in clades using an IS-printing system. IS-printing was previously developed as a relatively quick and easy tool for analysis of insertion sequence 629 in the O157 genome. Since most local government public health institutes in Japan carry out IS-printing for early detection of O157 outbreaks, these data should be useful for putative classification of O157 strains in each area.

Analysis of the population genetics of clades of enterohaemorrhagic Escherichia coli O157:H7/H- isolated in three areas in Japan.

AIMS: The genetic differences of enterohaemorrhagic Escherichia coli O157 (O157) strains isolated from humans in three widely-separated areas in Japan were analysed to provide information on possible geographic aspects of O157 pathogenicity. METHODS AND RESULTS: Epidemiologically unlinked O157 strains were isolated in Chiba (300 strains), Fukuoka (260 strains) and Yamagata (81 strains) prefectures. These strains were classified in clades by single nucleotide polymorphism in seven loci and lineage-specific polymorphism assay-6, and differences between the strains in each clade were compared by population genetic analyses using the IS-printing system. Analysis of the clades from the three areas showed linkage disequilibrium of the strains in each clade. Comparison of the genetic differences of strains from the three areas in each clade, from calculated ΦPT values, indicated that the strains in each clade were the same population in all three areas, except possibly the clade 12 strains. CONCLUSIONS: Population genetics analyses confirmed that the distribution of O157 strains in the clades isolated in three areas in Japan were similar and stable. SIGNIFICANCE AND IMPACT OF THE STUDY: The pathogenicity of O157 strains infecting humans was comparable due to the similar, stable geographic distribution of O157 clades.

Survival analysis of platinum-refractory patients with advanced esophageal cancer treated with docetaxel or best supportive care alone: a retrospective study.

The survival benefit of second-line chemotherapy with docetaxel in platinum-refractory patients with advanced esophageal cancer (AEC) remains unclear. A retrospective analysis of AEC patients with Eastern Cooperative Oncology Group performance status (PS)≤2 was performed, and major organ functions were preserved, who determined to receive docetaxel or best supportive care (BSC) alone after failure of platinum-based chemotherapy. The post-progression survival (PPS), defined as survival time after disease progression following platinum-based chemotherapy, was analyzed by multivariate Cox regression analysis using factors identified as significant in univariate analysis of various 20 characteristics (age, sex, PS, primary tumor location, etc) including Glasgow prognostic score (GPS), which is a well-known prognostic factor in many malignant tumors. Sixty-six and 45 patients were determined to receive docetaxel and BSC between January 2007 and December 2011, respectively. The median PPS was 5.4 months (95% confidence interval [CI] 4.8-6.0) in the docetaxel group and 3.3 months (95% CI 2.5-4.0) in the BSC group (hazard ratio [HR] 0.56, 95% CI 0.38-0.84, P=0.005). Univariate analysis revealed six significant factors: treatment, PS, GPS, number of metastatic organs, liver metastasis, and bone metastasis. Multivariate analysis including these significant factors revealed three independent prognostic factors: docetaxel treatment (HR 0.62, 95% CI 0.39-0.99, P=0.043), better GPS (HR 0.61, 95% CI 0.46-0.81, P=0.001), and no bone metastasis (HR 0.31, 95% CI 0.15-0.68, P=0.003). There was a trend for PPS in favor of the docetaxel group compared with patients who refused docetaxel treatment in the BSC group (adjusted HR 0.61, 95% CI 0.29-1.29, P=0.20). Docetaxel treatment may have prolonged survival in platinum-refractory patients with AEC.

Chronological changes of delayed-type hypersensitivity in mice immunised with testicular germ cells alone.

Experimental autoimmune orchitis (EAO), comprising a breakdown of the testicular immune privilege, is one of the models of immunological male infertility. EAO is characterised by CD4 + T-cell-dependent lymphocytic inflammation and augmented delayed-type hypersensitivity (DTH) against testicular antigens. We previously established an EAO model in mice by immunisation with viable syngeneic testicular germ cells (TGC) alone. However, the sequential change of DTH during development of this EAO has not been analysed yet. In this study, the DTH response during TGC-induced EAO was investigated by the injection of syngeneic TGC protein into the ears of mice. The results showed that a significant DTH response was observed on injection of 20 µg TGC protein, but not on that of 0.2 or 2 µg TGC protein. Also, the level of the DTH response to 20 µg TGC protein was highly relevant to the pathology of EAO development. These results indicate that the DTH response on injection of 20 µg TGC protein into the ears of mice is effective for predicting the pathology of EAO development.

Cervical curvature variations in patients with infraocclusion.

The purpose of this study was to observe the variations of cervical curvature in patients with infraocclusion, and to compare this with the controls. In this study, the infraocclusion criteria were defined with the Pr-id as <17 mm on the cephalometric image. The subjects were 32 patients with infraocclusion, and 28 controls which matched the distribution for gender and age. The six points of inquiry were as follows: (i) cervical vertebra height, (ii) neck alignment, (iii) ratio of lower facial height, (iv) vertical dimension of occlusion, (v) cervical angle and (vi) occlusal angle. In over 90% of the patients with infraocclusion, the cervical curvature was classified as straight or kyphosis. Conversely, in 36% of the control subjects, the cervical curvature was classified as lordosis. There was a weak positive correlation between the vertical dimension of occlusion and the cervical curvature in all subjects. In the control group, there was a significant and strong positive correlation between the age and cervical curvature, and a strong negative correlation between age and cervical angle and occlusal angle. Conversely, in the patients with infraocclusion, age was only correlated with the ratio of lower facial height. The prevalence of non-lordosis in the patients with infraocclusion was higher in comparison with the control group in our study, and the previous large-scale study of Japanese. However, there was merely a weak positive correlation between the cervical curvature and the vertical dimension of occlusion.

Comparison between the effects of epidural and intravenous patient-controlled analgesia on postoperative disability-free survival in patients undergoing thoracic and abdominal surgery: A post hoc analysis.

BACKGROUND: Thoracic epidural analgesia (TEA) and intravenous patient-controlled analgesia (IV-PCA) are widely used to mitigate immediate postoperative pain; however, their effects on long-term disability-free survival are poorly documented. This study aimed to compare the effects of postoperative TEA and IV-PCA on disability-free survival in patients who underwent thoracic or abdominal surgery. METHODS: This post hoc analysis of a prospective observational study included 845 inpatients aged ≥55 years that underwent elective thoracic and abdominal surgery between 1 April 2016 and 28 December 2018 in a tertiary care hospital. Inverse probability of treatment weighted (IPTW) using stabilized inverse propensity scores was adopted to minimize bias. The primary outcome in this study was disability-free survival, defined as survival with a 12-item World Health Organization Disability Assessment Schedule 2.0 score of <16%, assessed at 3 months and 1 year after surgery. RESULTS: The final analysis included 601 patients who received TEA and 244 who received IV-PCA. After IPTW, the weighted incidence of disability-free survival at 3 months and 1 year was 60.5% and 61.4% in the TEA group and 78.3% and 66.2% in the IV-PCA group, respectively. The adjusted OR for disability-free survival at 3 months and 1 year was 0.84 (95% confidence interval [CI]: 0.50-1.39) and 1.21 (95% CI: 0.72-2.05), respectively, for the TEA group. CONCLUSION: No significant differences were observed in the disability-free survival at 3 months and 1 year after elective thoracic and abdominal surgery in patients aged ≥55 years who received TEA or IV-PCA. SIGNIFICANCE STATEMENT: This study is the first in our setting to document the long-term effects of patient-controlled analgesia. In a post hoc analysis of our prospective cohort study, we show that although differences in chronic postsurgical pain exist at 3 months post-surgery, disability-free survival rates at 1 year do not differ irrespective of the choice of patient-controlled analgesia. The findings of this study highlight the need for shared decision-making between clinicians and patients.

[Surgical resection of a pulmonary pleomorphic carcinoma involving the azygos vein].

We report a case of surgical treatment of pulmonary pleomorphic carcinoma invading the azygos vein. Chest computed tomography (CT) revealed a mass of 6 cm in size, in the upper lobe of the right lung. He underwent the right upper lobectomy and lymph node dissection with combined resection of the involved azygos vein. Histological examination revealed pleomorphic carcinoma (pT3N0M0, stage IIB). The postoperative course was uneventful, and he was alive without recurrence 26 months after the operation. Six cases of pleomorphic carcinoma have been surgically treated between June 2008 and August 2009 in our institute. Early diagnose with complete resection is suggested to be essential in the improvement of survival for this disease based on review of our experience.

An atypical PKC directly associates and colocalizes at the epithelial tight junction with ASIP, a mammalian homologue of Caenorhabditis elegans polarity protein PAR-3.

Cell polarity is fundamental to differentiation and function of most cells. Studies in mammalian epithelial cells have revealed that the establishment and maintenance of cell polarity depends upon cell adhesion, signaling networks, the cytoskeleton, and protein transport. Atypical protein kinase C (PKC) isotypes PKCzeta and PKClambda have been implicated in signaling through lipid metabolites including phosphatidylinositol 3-phosphates, but their physiological role remains elusive. In the present study we report the identification of a protein, ASIP (atypical PKC isotype-specific interacting protein), that binds to aPKCs, and show that it colocalizes with PKClambda to the cell junctional complex in cultured epithelial MDCKII cells and rat intestinal epithelia. In addition, immunoelectron microscopy revealed that ASIP localizes to tight junctions in intestinal epithelial cells. Furthermore, ASIP shows significant sequence similarity to Caenorhabditis elegans PAR-3. PAR-3 protein is localized to the anterior periphery of the one-cell embryo, and is required for the establishment of cell polarity in early embryos. ASIP and PAR-3 share three PDZ domains, and can both bind to aPKCs. Taken together, our results suggest a role for a protein complex containing ASIP and aPKC in the establishment and/or maintenance of epithelial cell polarity. The evolutionary conservation of the protein complex and its asymmetric distribution in polarized cells from worm embryo to mammalian-differentiated cells may mean that the complex functions generally in the organization of cellular asymmetry.

Presenilin 1 suppresses the function of c-Jun homodimers via interaction with QM/Jif-1.

Presenilin 1 (PS1) is the causative gene for an autosomal dominant familial Alzheimer's disease (AD) mapped to chromosome 14. Here we show that QM/Jun-interacting factor (Jif)-1, a negative regulator of c-Jun, is a candidate to mediate the function of PS1 in the cell. We screened for proteins that bind to PS1 from a human embryonic brain cDNA library using the two-hybrid method and isolated one clone encoding the QM/Jif-1 gene. The binding of QM/Jif-1 to full-length PS1 was confirmed in vitro by pull-down assay, and in vivo by immunoprecipitation assays with human samples, including AD brains. Immunoelectronmicroscopic analysis showed that QM/Jif-1 and PS1 are colocalized at the endoplasmic reticulum, and the nuclear matrix in human brain neurons. Chloramphenicol acetyltransferase assays in F9 cells showed that PS1 suppresses transactivation by c-Jun/c-Jun but not by c-Jun/c-Fos heterodimers, consistent with the reported function of QM/Jif-1. By monitoring fluorescent recombinant protein and by gel mobility shift assays, PS1 was shown to accelerate the translocation of QM from the cytoplasm to the nucleus and to thereby suppress the binding of c-Jun homodimer to 12-O-tetradecanoylphorbol-13- acetate (TPA)-responsive element (TRE). PS1 suppressed c-jun-associated apoptosis by retinoic acid in F9 embryonic carcinoma cells, whereas this suppression of apoptosis is attenuated by mutation in PS1. Collectively, the novel function of PS1 via QM/Jif-1 influences c-jun-mediated transcription and apoptosis.

Differential targeting of protein kinase C and CaM kinase II signalings to vimentin.

Hydrolysis of inositol phospholipids by receptor stimulation activates two separate signaling pathways, one leading to the activation of protein kinase C (C kinase) via formation of diacylglycerol. The other is the inositol trisphosphate (IP3)/Ca2+ pathway and a major downstream kinase which is activated is Ca2+/calmodulin-dependent protein kinase II (CaM kinase II). To examine signaling pathways of C kinase and CaM kinase II to the cytoskeletal protein vimentin, we prepared monoclonal antibodies YT33 and MO82 which recognize the phosphorylation state of vimentin by C kinase and by CaM kinase II, respectively. Ectopic expression of constitutively active C kinase or CaM kinase II in primary cultured astrocytes by microinjection of the corresponding expression vectors induced phosphorylation of vimentin at each specific phosphorylation site, followed by reorganization of vimentin filament networks. In contrast, simultaneous activation of C kinase and CaM kinase II by inositol phospholipid hydrolysis with receptor stimulation led to an exclusive phosphorylation of vimentin at the CaM kinase II site, not at the site of C kinase. These results indicate that the intracellular targeting of C kinase and CaM kinase II signalings to vimentin is regulated separately, under physiological conditions.

A case of obstructive sleep apnoea with anterior cervical osteophytes.

Osteophytes of the cervical spine are usually seen in elderly adults. When prominent, they have been blamed for dysphagia, cough, dysphonia and dyspnoea. This paper reports on an obstructive sleep apnoea (OSA) patient with cervical spinal osteophytes, one cause of airway obstruction. A 75-year-old male complained of pronounced snoring. The diagnosis was mild OSA, apnoea hypopnoea index was 9.4. Patient reported no restrictions in neck movements, experiences of neck pain or neck trauma. Previously, patient underwent a tonsillectomy due to discomfort in the pharyngeal region. A lateral cephalometric image was taken to observe airway before oral appliance therapy. The image revealed the presence of large osteophytes or sclerotic enthesopathy, lying on anterior surfaces from the fourth to seventh cervical vertebrae. A computed tomography (CT) image revealed the relationship of airway position to the spine. In the reconstructed three-dimensional (3D) image, the airway appeared displaced to the right of the craniomandiblar bone, with the hyoid bone similarly displaced in a manner to that of the airway. The spine also appeared displaced to the left side ofcraniomandiblar bone. Additionally, the 3D image revealed calcification of the stylohyoideum ligament and ligamentum nuchae. This present case highlights the necessity of CT examination for OSA patients. There were several ligament calcifications in the head and neck region. Cervical spine osteophytes, as a component of Forestier's or cervical spine disease, have been associated with dysphagia and dysphonia. It was reported that bilateral vocal cord paralysis was caused by osteophytes compressing the post-cricoid area of larynx.

Preparation of silk resins by hot pressing Bombyx mori and Eri silk powders.

We investigate the mechanical properties and structure of silk resins as potential alternatives to tortoiseshell for producing eyeglass frames and various ornaments. Silk powders are obtained from Bombyx mori and Eri silk waste fibers before the degumming process. The powders are fabricated into resins via simple hot pressing under a pressure of 31.2 MPa at temperatures in the range 150-180 °C. The results indicate that the B. mori resins have higher micro-Vickers hardness, three-point bending strength, and elastic modulus (66 Hv, 122 MPa, and 8.7 GPa, respectively) compared to the Eri silk resins (58 Hv, 95 MPa, and 8.2 GPa, respectively). The better mechanical properties of the fibroin resins are related directly to longer drying times. The optimum drying conditions are found to be at a temperature of 100 °C under a-vacuum of -0.1 MPa for a time of 7 d. ATR-FTIR and XRD results show how the fibroin structure changes after resinification and drying. The morphology and the distribution size of particle of the silk powders and the fractured surfaces of the resins are analyzed from SEM micrographs. The present findings demonstrate that silk resins are suitable materials for developing useful applications because of their favorable mechanical properties.

[Multiple myeloma presenting as a solitary tumor of the rib; report of a case].

A 78-year-old man complained of right lateral chest pain. Chest X-ray showed an abnormal shadow in the right upper lung field and chest computed tomography (CT) scan showed a lateral chest wall tumor sorrouding the right 4th rib. Bone scintigraphy revealed only one lesion in the right 4th rib. Chest wall tumor resection was done. Histological analysis of the tumor specimen showed plasmacytoma. After the operation, the diagnosis of multiple myeloma was established by demonstration of myeloma by a bone marrow biopsy. Multiple myeloma should be taken into account as one of causes of a chest wall tumor even if it is a solitary tumor of the rib.

Association between sialyl Lewis(a) expression and tumor progression in melanoma.

Twenty-three primary and 27 metastatic melanoma lesions and 17 pigmented nevi lesions were tested utilizing the immunoperoxidase reaction with anti-sialyl Lewis(a) (sLea) and anti-sLex mAbs.sLea was expressed in 9, 25, and 5 and sLex was expressed in 6, 11, and 2 of these lesions, respectively. Expression of sLea in melanocytic tumors is associated with tumor progression. Serum levels of sLea and sLex were analyzed by a sandwich assay using mAbs in 25 melanoma patients. Only 2 patients at stage 4 showed higher levels of sLea and sLex than did normal control subjects. Moreover, sLea and sLex were expressed in 1 and 2 of 5 human melanoma cell lines, respectively, and expression of sLex and sLex was not modulated by cytokines. These findings suggest that the expression of sLea in melanocytic tumors is correlated with disease progression.

Kinetics of the immune response and regression of metastatic lesions following development of humoral anti-high molecular weight-melanoma associated antigen immunity in three patients with advanced malignant melanoma immunized with mouse antiidiotypic monoclonal antibody MK2-23.

Active specific immunotherapy has been implemented in patients with advanced malignant melanoma, utilizing the mouse antiidiotypic (anti-id) monoclonal antibody (mAb) MK2-23 which bears the internal image of high molecular weight-melanoma associated antigen (HMW-MAA). In a previous study, development of anti-HMW-MAA immunity in patients with advanced malignant melanoma immunized with anti-id mAb MK2-23 was found to be associated with a statistically significant survival prolongation. Since no information is available about the relationship between development of immunity and clinical response in patients immunized with anti-id mAb, the present study has characterized the kinetics of the immune response in three patients with advanced malignant melanoma who experienced regression of metastatic lesions following immunization with the anti-id mAb MK2-23. The three patients developed anti-mouse IgG antibodies, anti-anti-id antibodies and anti-HMW-MAA antibodies. The anti-HMW-MAA antibodies are mainly IgG, suggesting that the immune response elicited by anti-id mAb MK2-23 is T-cell dependent. The development of anti-HMW-MAA immunity preceded the reduction in the size of metastatic lesions. This temporal relationship suggests but does not prove that the anti-HMW-MAA immunity elicited by anti-id mAb MK2-23 has a beneficial effect on the clinical course of the disease in patients with malignant melanoma. This finding in conjunction with minor side effects associated with repeated administrations of mouse anti-id mAb MK2-23 suggest that active specific immunotherapy with anti-id mAb which bear the internal image of melanoma-associated antigen represents a viable therapeutic approach to malignant melanoma.

Modulation by adjuvants and carriers of the immunogenicity in xenogeneic hosts of mouse anti-idiotypic monoclonal antibody MK2-23, an internal image of human high molecular weight-melanoma associated antigen.

The mouse anti-idiotypic monoclonal antibody (mAb) MK2-23 recognizes an idiotope in the antigen-combining site of the immunizing anti-human high-molecular-weight melanoma-associated antigen (HMW-MAA) mAb 763.74. Administration with an adjuvant of mAb MK2-23 conjugated to a carrier has been shown to induce anti-HMW-MAA antibodies both in syngeneic hosts and in patients with malignant melanoma. Adjuvant and carrier are required for the induction of anti-HMW-MAA immunity in BALB/c mice immunized with mAb MK2-23. Whether both adjuvant and carrier are required also in patients with malignant melanoma is not known and cannot be deduced from results obtained in a syngeneic animal model system. Therefore the present study has evaluated for the first time the effect of a carrier and an adjuvant on the immunogenicity of mAb MK2-23 in a xenogeneic host. Rabbits were selected for this purpose, since they have a constitutive expression of HMW-MAA in their normal tissues with a distribution similar to that in humans. The combined use of an adjuvant and a carrier enhances the immunogenicity of mAb MK2-23 in rabbits markedly more than each of them individually. Specifically, all the rabbits immunized with mAb MK2-23 conjugated to keyhole limpet hemocyanin (KLH) and mixed with Freund's adjuvant (FA) produced antibodies which were shown with serological and immunochemical assays to be specific for HMW-MAA and to be both IgG and IgM. In contrast anti-HMW-MAA antibodies were detected in only one of the 3 rabbits immunized with mAb MK2-23 mixed with FA and were not detected in the rabbits immunized with mAb MK2-23 conjugated to KLH or with mAb MK2-23 without KLH and FA. These results indicate that active specific immunotherapy with mAb MK2-23 in patients with malignant melanoma is likely to benefit from the use of a carrier and an adjuvant, provide additional evidence that mAb MK2-23 bears the internal image of HMW-MAA, and suggest that the immune response elicited by mAb MK2-23 is T-cell dependent.

Ganglioside, adhesion molecule, and HLA antigen expression in basal cell carcinoma lesions.

The antigenic profile of basal cell carcinoma (BCC) cells was analyzed by immunoperoxidase staining of 27 surgically removed BCC lesions with antiganglioside, antiadhesion molecule, and antihistocompatibility locus antigen (HLA) monoclonal antibodies (MoAb). The large majority of BCC lesions were stained by antiganglioside MoAb; among the latter the anti-GD3 ganglioside MoAb R24 displayed the broadest reactivity. The GD3 ganglioside expression by BCC cells, which was corroborated by thin layer chromatography immunostaining with MoAb R24, appears to be a proliferation dependent phenomenon. Among the adhesion molecules tested vitronectin receptor and CDw44 were found in up to 70% of the lesions tested, while intercellular adhesion molecule 1 (ICAM-1) was detected in only a low percentage of BCC cells in one lesion. ICAM-1 was not induced on BCC cells in five and three lesions removed 24 and 48 h, respectively, following the intralesional injection of gamma-interferon. The latter enhanced HLA Class I antigen expression and induced ICAM-1 expression by the surrounding keratinocytes; furthermore gamma-interferon induced HLA Class II antigen expression by a small percentage of BCC cells in three lesions. These results suggest that malignant transformation of keratinocytes is associated with a selective loss of susceptibility to induction by cytokines of ICAM-1 expression. Besides confirming the low HLA Class I and Class II antigen expression by BCC cells, the present investigation has shown a differential expression of distinct monomorphic determinants of HLA Class I antigens and a lower expression of HLA-A antigens than of HLA-B antigens by BCC cells. Furthermore, the present study has shown that HLA Class II antigens can be induced on BCC cells by cytokines.

Both Jun and Fos contribute to transcription activation by the heterodimer.

Comparison of the amino acid sequence of the three members of the mouse jun proto-oncogene family, c-jun, jun B and jun D, reveals several homologous segments. The most C-terminal of them including a leucine zipper motif and a cluster of basic amino acids was previously identified as the DNA binding domain. By deletion analysis, we show that three conserved domains in the N-terminal region are crucial for transactivation by Jun homodimers. Only one of these is predicted to form an acidic amphipathic alpha-helix. The addition of Fos and the formation of Jun-Fos heterodimers strongly increases the transactivation level. Jun mutants that are inactive alone gain partial or full activity in the presence of Fos. This increase strongly depends on the presence of the C-terminal domain of Fos. These results show that in Jun-Fos heterodimers both the N-terminal part of Jun and the C-terminal part of Fos contribute to transactivation with a more pronounced role for the latter.