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J Bayer

Publications and source records attributed to J Bayer.

At least 19 recordsLinked to original sources

In vivo blockade of macrophage migration inhibitory factor prevents skin graft destruction after indirect allorecognition.

BACKGROUND: The effector mechanisms that ultimately destroy transplanted tissues are poorly understood. In particular, it is not clear how CD4+ T cells primed to donor-derived determinants expressed on recipient MHC molecules (the indirect pathway) can mediate graft destruction in the absence of cognate recognition of peptide: MHC on the graft cells themselves. Macrophage migration inhibitory factor (MIF) inhibits macrophage movement and is a proinflammatory and regulatory cytokine known to be essential for development of delayed-type hypersensitivity reactions. METHODS: To test whether MIF participates in graft destruction following indirect recognition, we studied rejection of MHC-II-deficient skin grafts placed on allogeneic SCID recipients adoptively transferred with naïve CD4+ T cells, and the recipients were treated with neutralizing anti-MIF monoclonal antibody or isotype control IgG. In this model graft rejection can only occur indirectly as the graft cells lack MHC II for recognition by the recipient CD4+ T cells. RESULTS: We found that in vivo blockade of MIF inhibited indirect CD4+ cell-mediated skin graft destruction, and markedly reduced detectable macrophages within the grafts. The neutralizing anti-MIF antibody significantly inhibited alloreactive DTH but did not prevent T cell priming or interferon-gamma release by primed T cells. CONCLUSIONS: The results strongly implicate MIF as an active participant in skin graft destruction after indirect recognition and suggest that this effect is mediated through an inhibition of macrophage migration and/or function.

Animals↗

Identification of homozygous deletions at chromosome 16q23 in aflatoxin B1 exposed hepatocellular carcinoma.

Loss of heterozygosity (LOH) represents the most frequent genetic alteration observed in hepatocellular carcinoma (HCC). Chromosome 16q is of particular interest as it exhibits LOH in 29% of HCC tumors and is frequently lost in breast, prostate, ovarian and gastric carcinomas. We genotyped 157 HCC tumors for 17 microsatellite markers distributed on chromosome 16q and determined a common region of LOH localized between the markers D16S518 and D16S504. By refining the boundaries of two interstitial LOH and two homozygous deletions, the critical region was delimited to 180 kb between D16S3096 and D16S3029. This region is located in intron 8 of the WWOX/FOR gene, but a search for mutations in all coding exons of this gene in 27 HCC tumors and cell lines did not reveal any tumor somatic alterations. Furthermore, by RT-PCR, no abnormal transcripts of this WWOX/FOR gene was detected in nine HCC cell lines. Finally, analysis of the p53 gene mutations with the clinical parameters of all tumors revealed that the two homozygous deletions have occurred in tumors presenting a R249S mutation. Our data revealed a relationship between chromosome 16q homozygous deletions and R249S p53 mutations in tumors where the patient had been exposed to aflatoxin B1 (P=0.002). These results are consistent with a role of aflatoxin B1 in the instability of chromosome 16q at the fragile site FRA16D. However, the nature of the specific gene that is altered during hepatocarcinogenesis remains to be elucidated.

Aflatoxin B1↗

Case and reanalysis.

In this paper we discuss an asymmetry in the Case system of German and its implications for human sentence processing: the asymmetry between nominative/accusative and dative case. Starting from the assumption that dative case has a distinct grammatical representation--dative DPs are embedded into an extra structural layer KP--the results of two experiments will be presented, which show that dative assignment during reanalysis is accompanied by additional processing operations that are not needed when accusative or nominative are assigned. In particular, we show that dative assignment during reanalysis triggers reaccess to the mental lexicon, giving rise to greater processing difficulty. We conclude with a discussion of empirical and theoretical consequences of our findings.

Humans↗

Beta-catenin mutations in hepatocellular carcinoma correlate with a low rate of loss of heterozygosity.

To determine the frequency of Wnt/Wingless beta catenin pathway alteration in human hepatocellular carcinoma, a beta catenin and APC gene mutation screening was performed in a series of 119 tumors. An activating beta catenin mutation in exon 3 was found in 18% of the cases. Among tumors lacking beta catenin mutation, no APC mutation has been evidenced in a subset of 30 cases tested. The correlation between beta catenin mutation status and chromosome segment deletions was studied on a set of 48 hyperploid tumors. Chromosome 1p, 4q and 16p deletions were significantly associated with the absence of beta catenin mutation (P<0.05). Furthermore the Fractional Allelic Loss was significantly smaller in the beta catenin mutated tumors than in the non-mutated tumors (0.12 versus 022). Taken together, these results suggest, the existence of two carcinogenesis mechanisms. The first mechanism implies a beta catenin activating mutation associated with a low rate of loss of heterozygosity. The second mechanism, operating in a context of chromosomal instability, would involve tumor suppressor genes.

Aneuploidy↗

[Semi-automated quantitative method for detecting the loss of heterozygosity at the long arm of chromosome 4 in hepatocellular carcinoma].

OBJECTIVES: Chromosomal deletions are the most frequent genetic alterations observed in hepatocellular carcinoma. Loss of heterozygosity on chromosome 4q has been observed in 40% of hepatocellular carcinomas suggesting the presence of a tumor suppressor gene which has not yet been identified. METHODOLOGY: We developed a semi-automated quantitative genotyping method which allowed us to characterize 119 hepatocellular carcinomas with 22 fluorescent microsatellite markers distributed on chromosome 4q. RESULTS: 4q loss was observed in 40% of cases. Among these deletions, 19 cases of partial or interstitial loss made it possible to define two common minimal regions of deletion of 25.1 and 37.6 centimorgans localized between markers D4S414 and D4S430 and between markers D4S3033 and D4S408, respectively. CONCLUSION: This work represents the first step towards the identification and characterization of new genes involved in hepatic carcinogenesis.

Adult↗

Efficient transduction of hemopoietic CD34+ progenitors of human origin using an original retroviral vector derived from Fr-MuLV-FB29: in vitro assessment.

A novel retroviral vector has been designed based on a Friend-murine leukemia virus (Fr-MuLV) FB29 strain. The latter has been selected according to characteristics of pathogenicity in mice where it induces a disease of the haemopoietic system affecting all lineages. Higher infectivity has also been demonstrated as compared to other strains. In accordance with these findings, the amphotropic producer clone used in this study carrying along the neomycine resistance gene (FOCH-Neo), harbors viral titers over 10(7) cfu/ml. To investigate the potential of genetically engineering hematopoietic precursors, CD34+ progenitors were selected from cord blood, bone marrow, and peripheral blood mobilized stem cells (patients + solid tumors) and transduced with FOCH-Neo. High transduction rates were achieved using virus supernatant and minimal doses of hematopoietic growth factors during pretransduction and transduction steps. A polymerase chain reaction (PCR) assay investigating the presence of both neomycin-encoding and viral vector sequences tested positive in 45-90% of granulocyte-macrophage colony-forming units (CFU-GM) generating cells (bone marrow and peripheral blood derived cells) following transduction. An average of 35% colonies showed resistance to G418. Such levels of transduction proved reproducible using only supernatants harboring over 10(7) cfu/ml. In those experiments where long-term in vitro cultures could be maintained over 5 weeks (all cord blood and 5 among 23 PBSC), efficient transduction of long-term culture initiating cell (LTC-IC) hematopoietic progenitors was demonstrated on the basis of both resistance to G418 and virus integration. In the latter case, the PCR assay tested positive in as much as 35-60% of late unselected CFU-colonies. This novel retroviral vector harbors interesting features toward genetic modification of hematopoietic progenitors.

3T3 Cells↗

Laser lithotripsy of difficult bile duct stones: results in 60 patients using a rhodamine 6G dye laser with optical stone tissue detection system.

INTRODUCTION: Laser lithotripsy of bile duct stones has become a widely accepted endoscopic treatment modality for giant, impacted, or very hard stones. The procedure is usually carried out under direct endoscopic control in view of the potential risk of bile duct injuries in "blind" laser application. AIMS: To investigate the use of a rhodamine 6G laser lithotriptor with an integrated optical stone tissue detection system (oSTDS). METHODS: From 1 September 1991 to 7 March 1997, 60 patients with giant or impacted common bile duct stones refractory to endoscopic papillotomy stone extraction, and mechanical lithotripsy were treated via the endoscopic retrograde route using a rhodamine 6G dye laser (595 nm, 2.5 micros, 80-150 mJ pp, Lithognost Telemit/Baasel Corp., Germany) with integrated oSTDS. In case of tissue contact oSTDS cuts off the laser pulse after 190 ns (transmission of 5-8% of the total pulse energy). 47 patients (78.3%) were subjected to x ray targeting (oSTDS) alone, five (8.3%) to choledochoscope targeting alone, and eight (13.3%) to both techniques. RESULTS: At the end of treatment 52 (87%) patients were completely stone-free. The only major complications included transient haemobilia, cholangitis, and pancreatitis in five patients. All five were successfully treated by conservative methods. CONCLUSIONS: Laser lithotripsy using the described rhodamine 6G dye laser with oSTDS seems to be safe and effective and allows "blind" fragmentation of difficult common bile duct stones under radiological control only.

Adult↗

Event-related brain potentials and case information in syntactic ambiguities.

In an ERP study, German sentences were investigated that contain a case-ambiguous NP that may be assigned accusative or dative case. Sentences were disambiguated by the verb in final position of the sentence. As our data show, sentences ending in a verb that assigns dative case to the ambiguous NP elicit a clear garden-path effect. The garden-path effect was indicated by a broad centro-posterior negative shift that occurred between 300 and 900 msec after the dative-assigning verb was presented. No enhanced P600 following the misanalysis was observed. Noun phrases whose case ambiguity was resolved in favor of accusative case and unambiguously dative-marked NPs did not trigger significant ERP differences. We will discuss the implications of our results for parsing and its neuropsychological correlates. The results of this study support a parser design according to which the so-called structural case (nominative or accusative) is assigned without any delay in the absence of morpho-lexical counterevidence. It is argued that the enhancement of a negative ERP component with a "classical" N400 topography reflects the difficulty of reanalysis due to reaccessing morpho-lexical information that lies outside the domain of the parsing module. Consequently, ERP responses to garden-path effects are not confined to a late positivity but vary depending on the level of processing involved in reanalysis. The fact that garden-path effects may also elicit an N400 can be linked to the nonhomogeneous linguistic properties of the constructions from which they arise.

Adult↗

Total navy recruit health: making our sailors fit for the fleet.

Naval Hospital Great Lakes, Branch Medical Clinic, Recruit Training Command is the Navy's only recruit inprocessing point in the country. The clinic will medically inprocess approximately 54,000 new Navy recruits this year. In fiscal year 1995, the clinic inprocessed approximately 44,000 recruits, 35,000 males and 9,000 females. The Navy Medical Department is very concerned about total Navy recruit health. This includes a check on the present state of health of all sailors and teaching sailors how to stay healthy and take care of themselves during their naval careers. Navy medicine is also an integral part of the recruit training experience. Recruit training at Great Lakes is 9 weeks in duration. This article will describe the Navy's recruit medical inprocessing procedure to include the Sailor's Health Inventory Program, the Navy/Air Force Medical Entrance Test, immunizations, optometry, audiology, wellness education, gynecological examinations, medical assessment, and laboratory tests.

Female↗

[Herpes simplex keratitis. On the long-term prognosis of first transplants after penetrating keratoplasty].

Eighty-six consecutive first grafts performed between 1980 and 1990 (86 patients) for herpes simplex keratitis (HSK) were studied retrospectively (mean follow-up 4.1 years). Indications for penetrating keratoplasty (PKP) included: persistent inflammation, descemetocele or perforation (21/86); stromal opacities with vascularization (43/86), and avascular stromal opacities (22/86). The overall survival rate of clear transplants was 80% after 2 and 68% after 11 years. Corneal inflammation at the time of surgery was found to be a prognostic factor, but not corneal vascularization: The 2-year survival rates for clear grafts were 95% for avascular and 83% for vascularized stromal opacities in clinically inactive eyes, as against 58% for clinically active corneas at the time of surgery. HSV-specific structural proteins were immunohistochemically detectable most often in keratectomy specimens from patients with corneal inflammation before the operation (91%). In the group of clinically inactive stromal opacities, HSV antigens were detectable significantly (P < 0.001, chi-square test) more often in keratectomy specimens from patients with avascular opacities than in those with vascularized opacities. This may explain why corneal vascularization is not a significant risk factor for HSV recurrences. The different frequency of HSV-specific proteins in avascular and vascularized corneas merits attention in the intra- and postoperative management of patients with HSK undergoing corneal transplantation.

Adolescent↗

Progress in childhood cancer care in Florida. 1970-1992.

Pediatric cancer has been a priority in Florida since 1970. That year physicians established a statewide network of children's tumor programs, the Florida Association of Pediatric Tumor Programs (FAPTP), which has grown from the initial two programs to 10 in 1992 and now maintains a registry with follow-up to monitor incidence and other indicators. State-of-the-art care is provided through affiliation with the Pediatric Oncology Group. The incidence of pediatric cancer in Florida is equivalent to national rates, but the number of children followed in 1991 had grown to approximately 2,000. The number receiving care has increased an average of 13% annually since 1981. Services for these patients should be reviewed on a continuing basis to assure access to specialized programs.

Adolescent↗

The incidence of pediatric cancer in Florida, 1981 to 1986.

Incidence rates for pediatric (ages, 0 to 14 years) cancer in the state of Florida were produced for the period 1981 to 1986 and compared with national data to investigate variations in pediatric cancer incidence. Overall, Florida had an incidence rate of 12.77 per 100,000; this was not significantly higher than expected based on national rates (standardized incidence ratio, 1.0; 95% confidence interval, 0.9 to 1.0). Compared with national rates, whites residing in Florida had an increased rate of acute lymphocytic leukemia and decreased rate for soft tissue sarcomas (other than rhabdomyosarcoma), "other leukemias," and "other" cancers. Nonwhites residing in Florida had increased rates for soft tissue sarcomas (other than rhabdomyosarcoma) and decreased rates of "other" cancers. Boys in Florida had increased rates for retinoblastoma and acute lymphocytic leukemia and decreased rates for "other leukemias" and "other" cancers. Rates for girls were decreased for neuroblastoma and "other leukemias."

Adolescent↗

Culture of hematopoietic stem cells purified from murine bone marrow.

The results of the Y-chromosome in situ hybridization experiments, the MRA assessment, and the long-term production of CFU-GM in vitro indicate that our protocol to sort low density WGA+, 15/1.1-, Rh123 dull cells enriches about 200-fold for PHSC. Assays for spleen colony formation (CFU-S) and radioprotection (30-day survival) were shown to be unspecific for PHSC, and, therefore, we lack a quantitative PHSC assay. The absolute number of PHSC in the bone marrow is not known any more, the purity of our sorted population likewise is unknown. Long-term repopulating cells (PHSC) could be separated from short-term repopulating ones by using Rh123 staining. The short-term repopulating cells (Rh123 bright) provided sufficient offspring to protect lethally irradiated mice until endogenous PHSC could reconstitute hematopoiesis. These cells are therefore of interest for bone marrow transplantation, because they provide radioprotection without long-term repopulation and graft-versus-host disease. For gene therapy these cells are of limited use, and PHSC with extensive replication are needed. The PHSC were not cultured successfully. Less than 15% of the sorted Rh123 dull cells responded in semisolid or liquid cultures in the presence of growth factors. Proliferation without differentiation was not observed. This may indicate that the right growth factor has not been found yet. On the other hand, about 30% of the cells responded in stromal layers of long-term bone marrow cultures and prolonged CFU-GM production and cobblestone area formation were observed there, suggesting that cell-cell contact and adherence molecules play a regulatory role in PHSC replication.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗