Search PubMed⌕ Search

Biomedical subjects

R Wagner

Publications and source records attributed to R Wagner.

At least 217 records · Page 12Linked to original sources
PubMed1995

Inhibition of growth of a murine squamous cell carcinoma by a cyclooxygenase inhibitor increases leukotriene B4 production.

OBJECTIVE: To determine the role of metabolites of arachidonic acid in the growth of squamous cell carcinomas of the head and neck. DESIGN: Investigation of the effect of a cyclooxygenase inhibitor, piroxicam, on the growth of squamous cell carcinoma in a murine model. INTERVENTION: C3H/HeJ mice bearing squamous cell carcinoma (SCCVII) were treated with piroxicam (0.08 mg/d, orally) for 30 days beginning 1 day before tumor inoculation. MAIN OUTCOME MEASURES: Decrease in tumor volumes and tumor growth rates. RESULTS: Significant inhibition of tumor growth (P = .002) and final tumor weight (P = .0007) was noted in the group receiving piroxicam therapy. Prostaglandin E2 levels in the tumor tissue were unrelated to treatment or tumor size. Increased levels of leukotriene B4 were observed in the piroxicam-treated group (P = .03), and larger tumors were associated with decreased leukotriene B4 levels (P = .0001). CONCLUSIONS: Cyclooxygenase inhibitors may be effective in the treatment of some squamous cell carcinomas. The therapeutic effect of cyclooxygenase inhibitors may result from shunting into the lipoxygenase pathway of arachidonic acid metabolism.

Animals↗
PubMed1995

A reappraisal of the squamous cell carcinoma antigen as a tumor marker in head and neck cancer.

OBJECTIVE: To analyze serial measurements of squamous cell carcinoma antigen (SCCAg) to determine its prognostic significance in squamous cell carcinoma of the head and neck (SCCHN). DESIGN: Retrospective analysis of serial SCCAg measurements in 75 patients with squamous cell carcinoma of the head and neck. Serum samples were obtained preoperatively and at postoperative intervals ranging from 1 week to 36 months. Serum SCCAg levels were determined by radioimmunoassay. SETTING: Oncologic head and neck practice at a tertiary referral hospital. PATIENTS: Tumor Registry data of 75 consecutive patients with at least three postoperative SCCAg determinations were reviewed to provide equal numbers of patients with and without recurrent disease. All patients who remained disease-free were followed up for at least 2 years. All patients were previously untreated and underwent surgical therapy. MAIN OUTCOME MEASURES: Association of postoperative SCCAg levels and 2-year disease-free survival. RESULTS: No differences in preoperative levels were noted, but SCCAg levels predicted 2-year disease-free survival at 6, 9, and 12 months after surgery. The ratio of post-operative SCCAg levels to preoperative and early post-operative levels also provided prognostic information. CONCLUSIONS: Serial measurements of SCCAg postoperatively in patients with head and neck cancer predict outcome and may allow for earlier detection of recurrent disease. Further studies are needed to determine if earlier detection can be translated into improved survival.

Antigens, Neoplasm↗
PubMed1995

Linear gap and tight junctional assemblies between capillary endothelial cells in the eel rete mirabile.

BACKGROUND: Interendothelial tight junctions and gap junctions have been described in large blood vessels and in cultures of endothelium derived from large blood vessels. Transfer of microinjected small-molecular weight tracers between adjacent endothelial cells also has been demonstrated indicating the presence of gap junctional interendothelial communication. Similar transfer of tracers is evident between microvessel endothelial cells in culture and in microvessels in situ. However, gap junctions have not been detectable by electron microscopy of intact capillary systems. This may be due to limited sampling available in diffuse capillary systems and a small area of overlap between adjacent endothelial membranes. METHODS: Thin slices of the parallel, tightly packed capillary bed of the eel rete mirabile were cryofixed and prepared for conventional TEM by freeze-substitution. Other samples were freeze-fractured and replicated for examination of endothelial junctional components. RESULTS: A novel tight-gap junctional complex between rete capillary endothelial cells is described. In freeze-fracture replicas of the membrane P face, rows of gap junction subunits are flanked on either side by linear depressions representing grooves previously occupied by tight junctional strands that partition to the E face. In thin sections, the junctions appear in profile as short lengths of closely apposed membranes characteristic of gap junctions. CONCLUSIONS: The tight junctional components imply a barrier to paracellular transport across the capillary wall between the endothelial cells. The gap junctional component may provide a mechanism for communication between endothelial cells along the length of the vessel wall.

Air Sacs↗
PubMed1995

Peripheral nerve pathology following sciatic cryoneurolysis: relationship to neuropathic behaviors in the rat.

Sciatic cryoneurolysis (SCN) is an experimental rat mononeuropathy model that produces neuropathic behavioral sequelae distinct from other neuropathy models. Following SCN, there is limited autotomy peaking in severity and incidence at 7-14 days and delayed but sustained allodynia appearing at about 21 days, with no evidence of thermal hyperalgesia. This study quantified peripheral nerve pathology at weekly intervals following SCN to determine the relationship of nerve degeneration and regeneration to the resulting abnormal behaviors. Fiber histograms based on axon diameter and grid morphometry were used to quantify the pathologic state of nerve fibers, activated phagocytic cells, vessels, and edema at the lesion site. Approximately 90% of the axons demonstrated Wallerian-like degeneration by 3 days post-SCN. At 14 days, small diameter axons significantly increased in number from earlier times following SCN (P < 0.05) but were not significantly different from normal values. At 21 days, the number of small diameter axons was significantly increased over both 14 days (P < 0.05) and normal values (P < 0.05). At 28 days, intermediate diameter axons significantly increased in number with respect to all earlier time periods (P < 0.05). These increases in regenerating fibers overlapped with the development of peak autotomy at 7-14 days and the onset of allodynia after 21 days. Autotomy scores at 7 days positively correlated with grid morphometry data of regenerating axons (rho = 0.7) and activated macrophages and Schwann cells (rho = 0.8) and inversely correlated with edema (rho = -0.8) using Spearman's rank correlation analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Comparative analysis of Homo sapiens and Mus musculus cyclin-dependent kinase (CDK) inhibitor genes p16 (MTS1) and p15 (MTS2).

Cyclin-dependent kinase inhibitors are a growing family of molecules that regulate important transitions in the cell cycle. At least one of these molecules, p16, has been implicated in human tumorigenesis while its close homolog, p15, is induced by cell contact and transforming growth factor-beta (TGF-beta). To investigate the evolutionary and functional features of p15 and p16, we have isolated mouse (Mus musculus) homologs of each gene. Comparative analysis of these sequences provides evidence that the genes have similar functions in mouse and human. In addition, the comparison suggests that a gene conversion event is part of the evolution of the human p15 and p16 genes.

Amino Acid Sequence↗
PubMed1995

Autoantibodies to the islet antigen ICA69 occur in IDDM and in rheumatoid arthritis.

Islet cell antigen (ICA) 69 is a newly-recognized islet cell antigen to which autoantibodies have been observed in prediabetic relatives of patients with insulin-dependent-diabetes mellitus (IDDM). Here we extend the earlier analysis of ICA69 antibodies to patients with recent-onset IDDM and to patients with other immune-mediated diseases. ICA69 antibodies were determined by Western blot using an affinity purified recombinant fusion protein of ICA69 and maltose binding protein. ICA69 antibody quantities were determined as titres using a titration curve of a standard serum as reference. Mean logarithmic ICA69 antibody titres were 3.4 (+/- 1.4) in 99 patients with acute IDDM compared to 2.8 (+/- 0.9) in 49 healthy blood donors (p < 0.001). A higher mean ICA69 antibody titre of 4.1 (+/- 0.8) was observed in 16 patients with rheumatoid arthritis in comparison to acute IDDM (p < 0.01) and healthy control subjects (p < 0.001). The percentage of sera with ICA69 antibody titres above the 2 SD level of normal subjects was 21% in IDDM, 31% in rheumatoid arthritis and 6% in healthy blood donors. None of the patients with autoimmune thyroid disease (n = 20), inflammatory bowel disease (n = 9) or multiple sclerosis (n = 7) had elevated ICA69 antibodies. In IDDM, presence of ICA69 antibodies persisted and the titre remained the same over 18 months of follow-up. The relationship of ICA69 antibodies to islet cell antibodies (ICA) or insulin autoantibodies (IAA) was tested. The production of ICA69 antibodies was not associated in diabetic patients with the presence of any of the two other autoantibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Gender differences in autotomy following sciatic cryoneurolysis in the rat.

Gender differences reported in nociceptive and nerve injury research should be considered before conclusions about basic pathologic mechanisms are drawn. Holtzman male rats are routinely used in the mononeuropathy model produced by a peripheral nerve freeze lesion, sciatic cryoneurolysis (SCN). SCN reproducibly results in abnormal behaviors which include autotomy, the gnawing and scratching of the affected hindpaw. In the present studies, the incidence and severity of autotomy 1 to 21 days following SCN was compared in male and female Holtzman rats. Female Holtzman rats displayed a decreased incidence and severity of autotomy 7 days and beyond following SCN. This disparity was statistically different at 14 days (p < 0.01) and at 21 days (p < 0.05) by Newman-Keuls test. Morphometric comparison of the sciatic nerve at the lesion site in male and female rats 14 days post-SCN (time of peak autotomy behavior in this model) displayed differences in the fascicular percentage of edema (p < 0.01) and remyelinating axons (p < 0.05) between genders using Student's t-test. However, these percentage values did not correlate with either the incidence or severity of autotomy scores for those animals. Therefore, biochemical differences at and/or proximal to the peripheral nerve freeze lesion may be responsible for mechanisms which generate or relate to autotomy.

Animals↗
PubMed1995

Priming of class I-restricted cytotoxic T lymphocytes by vaccination with recombinant protein antigens.

We investigated the specific priming of MHC class I-restricted cytotoxic T lymphocytes (CTL) by different protein antigen preparations in mice. The recombinant viral protein antigens tested are of potential relevance for the design of subunit vaccines. They include the hepatitis B virus (HBV) surface antigen (S-antigen), the HIV-1 gp160 envelope protein, and a chimeric HIV-1 Pr55-gag/V3-3 retrovirus-like particle. In addition, ovalbumin (OVA) was tested. The native or denatured particulate (multimeric) or monomeric form of these protein antigens was injected by various routes into mice. Class I-restricted CTL were efficiently primed by a single low-dose injection of HBV S-antigen particles or the chimeric HIV-1 Pr55-gag/V3-3 particles. After SDS-denaturation, gel-purified monomeric S-antigen and monomeric Pr55-gag/V3-3 fusion protein were still very efficient in priming CTL. CTL sensitization was not detected in a (primary or boosted) response to even high doses of native OVA or native HIV-1 gp160. Denaturation of these two antigens by detergent strikingly increased their immunogenicity for CTL. Immunization of mice with non-treated or SDS-denatured antigenic peptides representing the relevant CTL-defined epitopes of the tested protein antigens did not prime CTL. These data indicate that native, particulate and denatured, monomeric protein antigens efficiently stimulate a class I-restricted CTL response.

Amino Acid Sequence↗
PubMed1995

Interactions between human bronchoalveolar macrophages and Blastomyces dermatitidis conidia: demonstration of fungicidal and fungistatic effects.

The effects of human bronchoalveolar macrophages (BAMs) on Blastomyces dermatitidis conidia were investigated. Macrophage monolayers were incubated for 5 days with or without interferon (IFN)-gamma or macrophage colony-stimulating factor (M-CSF) before challenge with conidia for 48 h at 37 degrees C. Hyphal growth (germination) was inhibited 12% by resident BAMs (P < .05). In contrast, resident BAMs blocked conidial phase transition by 88% (P < .05). Intermediate forms, aggregates of large cells in clums (not conidia or yeasts by morphologic criteria), appeared after incubation with BAMs and grew into typical yeasts once removed from the BAMs. IFN-gamma and M-CSF inhibited the ability of BAMs to block phase transition but not germination. Human BAMs demonstrated fungicidal and fungistatic activity against B. dermatitidis conidia independent of reactive oxygen intermediates and had greater effects on phase transition than on germination. The phase transition-associated fungicidal and fungistatic activities of BAMs were inhibited by IFN-gamma and M-CSF.

Blastomyces↗
PubMed1995

A prospective study of CD45 isoform expression in haemophagocytic lymphohistiocytosis; an abnormal inherited immunophenotype in one family.

In a prospective study, CD45 isoform expression on T lymphocytes was analysed in seven patients with haemophagocytic lymphohistiocytosis (HLH) and their family members. Six patients, their parents and seven healthy age-matched controls showed the normal pattern of three subpopulations of CD45R expression. In one patient, his mother and one of his healthy brothers only two subpopulations could be identified, which might indicate that the maturation from a CD45RA/RO double-positive to a CD45RO single-positive phenotype does not occur in these individuals. It is not clear if this finding had any impact on the development of HLH in this patient and if the pattern of CD45RA and RO expression observed in this family might represent a predisposition to HLH. In another patient a marked increase of the CD45RO single-positive T cell population was observed during a period of increased disease activity. The clinical relevance of this observation and whether CD45RO expression could serve as a marker for disease activity, or in selected individuals as a susceptibility marker for HLH, remain unknown.

Child↗
PubMed1995

Inhibition of dengue virus by novel, modified antisense oligonucleotides.

Five different target regions along the length of the dengue virus type 2 genome were compared for inhibition of the virus following intracellular injection of the cognate antisense oligonucleotides and their analogs. Unmodified phosphodiester oligonucleotides as well as the corresponding phosphorothioate oligonucleotides were ineffective in bringing about a significant inhibition of the virus. Novel modified phosphorothioate oligonucleotides in which the C-5 atoms of uridines and cytidines were replaced by propynyl groups caused a significant inhibition of the virus. Antisense oligonucleotide directed against the target region near the translation initiation site of dengue virus RNA was the most effective, followed by antisense oligonucleotide directed against a target in the 3' untranslated region of the virus RNA. It is suggested that the inhibitory effect of these novel modified oligonucleotides is due to their increased affinity for the target sequences and that they probably function via an RNase H cleavage of the oligonucleotide:RNA heteroduplex.

Alkynes↗
PubMed1995

Prognostic significance of prostaglandin E2 production by mononuclear cells and tumor cells in squamous cell carcinomas of the head and neck.

Prostaglandin E2 (PGE2) has been implicated as a cause of immunosuppression in patients with head and neck cancer. To determine the relative contribution of tumor cells and mononuclear cells to PGE2 levels in vivo, tumor cells and tumor-infiltrating mononuclear cells (TIMC) were isolated from fresh tumor biopsy specimens of 23 patients with squamous cell carcinoma of the head and neck (SCCHN) by using enzymatic digestion and differential gradient centrifugation. Peripheral blood mononuclear cells (PBMC) and lymph node mononuclear cells (LNMC) from metastatic and nonmetastatic lymph nodes were also isolated. Cell fractions were cultured for 24 hours, and PGE2 levels of supernatant were determined by radioimmunoassay. PGE2 production by LNMC was significantly decreased compared to tumor cells, TIMC, and PBMC (P = .0002). LNMC from metastatic lymph nodes produced significantly higher levels of PGE2 (P = .02) compared to nonmetastatic lymph nodes. Although T stage was not correlated with PGE2 production by TIMC or tumor cells, advanced N stage (N1-3) was associated with decreased PGE2 production by TIMC (P = .006). These results suggest that both tumor cells and TIMC are sources of PGE2 in tumor tissues of patients with SCCHN and that decreased PGE2 production by host inflammatory cells may have clinical significance in the development of cervical metastases.

Adult↗
PubMed1995

Flow cytometric analysis of primary and metastatic squamous cell carcinoma of the oral cavity and oropharynx.

A retrospective analysis of formalin-fixed, paraffin-embedded tissue from patients with histologically confirmed metastatic squamous cell carcinoma was performed using flow cytometry. Ninety-eight sets of specimens from previously untreated patients with an oral cavity or oropharyngeal tumor and a simultaneous cervical metastatic deposit were analyzed. Normal mucosa and cervical lymph nodes were processed identically and run as controls. All patients underwent surgical resection at Wilford Hall USAF Medical Center or The Eye and Ear Hospital of Pittsburgh between 1980 and 1986. The specimens from 94 patients were technically adequate for interpretation. Diploid histograms in both the primary and metastatic tumors were present in 49 (52%) of 94 patients. Aneuploid histograms in either the primary and metastatic tumors were noted in 45 (47%) of 94 patients. In this group of 45 patients, the primary tumor and cervical metastasis were both aneuploid in 21 (46%), and aneuploid histograms occurred with equal incidence in either the primary or metastasis in the remaining 24 cases. No statistically significant prediction of survival could be made from any correlation with the histograms of either the primary or metastasis. The potential technical problems and limitations of flow cytometry in the determination of DNA content of formalin-fixed, paraffin-embedded tissue and the selection of patients with advanced disease warrant caution in the interpretation of results.

Carcinoma, Squamous Cell↗
PubMed1995

[Mutism after posterior fossa tumor surgery. Report of 2 cases].

The authors present two cases of mutism after posterior fossa surgery. Two patients aged 16 and 5 years old respectively with astrocytoma and medulloblastoma, developed mutism after the operation. Topographic aspects of the condition are discussed and its neurological expression.

Adolescent↗
PubMed1995

Frequency of false-positive septal defects on adenosine/201T1 images in patients with left bundle branch block.

The exercise 201T1 imaging procedure in patients with left bundle branch block (LBBB) is associated with a relatively high frequency of false-positive septal perfusion defects. We therefore initiated a study designed to determine the frequency of false-positive septal defects seen with adenosine/thallium imaging. In total, 900 adenosine/thallium cases performed at our institution for assessment of coronary artery disease were reviewed. Sixty-eight patients had LBBB on resting electrocardiogram (ECG) and sucessfully completed the imaging procedure, of whom 25 had coronary angiography. Only 6 of the 68 patients demonstrated reversible septal defects on thallium imaging. Of these 6 patients, 3 underwent coronary angiography and all of them had significant (> 70%) LAD stenosis. Therefore, at most only 4% of the patients with LBBB had a false-positive reversible septal defect. Three additional patients had fixed septal defects. Of these three patients, one underwent cardiac catheterization and was found not to have significant LAD stenosis. The results from this study suggest that adenosine/thallium imaging is associated with an acceptably low frequency of false-positive septal defects and should be used as an alternative to exercise/thallium in patients with LBBB.

Adenosine↗
PubMed1995

High-resolution PET in cats: application of a clinical camera to experimental studies.

UNLABELLED: A commercial high-resolution scanner designed for clinical PET studies was tested for its applicability to investigate cerebral metabolism and blood flow in cats. METHODS: Cerebral blood flow, CMRO2, CBV and CMRglc were determined repeatedly using 15O steady-state oxygen methods and 18F-fluorodeoxyglucose (FDG). Metabolic and blood flow images of 14 contiguous 3-mm PET slices were compared to histological sections in four control animals. In another six cats, hemodynamic and metabolic changes were followed by serial multi-tracer PET for 24 hr after permanent occlusion of the left middle cerebral artery (MCA). Pattern and extent of changes of the physiological variables were related to the final infarct verified in matched histological sections. RESULTS: At spatial resolutions (FWHM) of 3.6 mm in transaxial planes and 4.0 mm axially, details of the gross anatomy of the cat brain were distinguished best in the FDG images. Cerebral blood flow, CMRO2 and CMRglc values measured in the cortex, white matter and basal ganglia were in the range of common autoradiographic results. Immediately after MCA occlusion, there was widespread decrease in blood flow, but metabolism was preserved at values, which suggest viable tissue. With time, the areas of increased oxygen extraction fraction (OEF) moved from the center to the periphery of the MCA territory. CONCLUSION: High-resolution PET can be used for repeat, quantitative imaging of blood flow and metabolism in small animals such as the cat. After MCA occlusion, the changes in blood flow and metabolism can be followed over time and can be related to the final morphological lesion.

Animals↗
PubMed1994

Predictors of automobile crashes and moving violations among elderly drivers.

OBJECTIVE: To identify the factors associated with automobile crashes, moving violations, and being stopped by police in a cohort of elderly drivers. DESIGN: Prospective cohort study. SETTING: Urban community. PARTICIPANTS: All 283 persons who drove between 1990 and 1991, selected from a representative cohort of community-living persons aged 72 years and older in New Haven, Connecticut. MEASUREMENTS: Data on independent variables in five domains (demographic, health, psychosocial, activity, and physical performance) were collected in structured interviews before events occurred. The outcome measure was the self-report of involvement in automobile crashes, moving violations, or being stopped by police in a 1-year period. RESULTS: Of the 283 drivers, 13% reported a crash, a moving violation, or being stopped by police in 1 year. The baseline factors associated with the occurrence of adverse events in multivariable analysis (with adjustment for driving frequency and housing type) were the following: poor design copying on the Mini-Mental State Examination (relative risk, 2.7; 95% CI, 1.5 to 5.0), fewer blocks walked (relative risk, 2.3; CI, 1.3 to 4.0), and more foot abnormalities (relative risk, 1.9; CI, 1.1 to 3.3). These risk factors were combined for assessment of their ability to predict the occurrence of adverse driving events. If no factors were present, 6% of drivers had events; if 1 factor was present, 12% had events; if 2 factors were present, 26% had events; and if 3 factors were present, 47% had events. CONCLUSIONS: In this urban population, several simple clinical measures correlated with the risk for adverse driving events.

Accidents, Traffic↗