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Biomedical subjects

D Martinez

Publications and source records attributed to D Martinez.

At least 91 records · Page 5Linked to original sources

Protection against papillomavirus with a polynucleotide vaccine.

Genital infections with human papillomavirus (HPV) are increasingly recognized as a significant source of human disease; HPV is now implicated in up to 90% of cervical carcinomas. Neutralizing antibodies against papillomaviruses recognize conformational epitopes formed when viral capsid proteins assemble into virions or virus-like particles. Immunization with plasmid DNA encoding the major viral capsid protein L1 was studied as a means of inducing neutralizing antibodies and protection against virus challenge. In a cottontail rabbit papillomavirus (CRPV) model, immunization with plasmid DNA encoding L1 elicited conformationally specific neutralizing antibodies and provided immunity against papilloma formation upon challenge with CRPV. Immunization with DNA encoding the capsid protein may provide a means of protecting humans against HPV and would simplify the production of multivalent vaccines by combining plasmids that encode the viral capsid proteins of different strains. This may be of importance given the multiplicity of HPV types capable of causing disease.

Animals↗

Infection of bovine brain microvessel endothelial cells with Cowdria ruminantium elicits IL-1 beta, -6, and -8 mRNA production and expression of an unusual MHC class II DQ alpha transcript.

Cowdria ruminantium is a bacterial parasite that infects ruminants, causing an acute and often fatal disease. These obligate intracellular Gram-negative bacteria preferentially infect neutrophils and vascular endothelial cells, especially in the brain. The present study was performed with bovine brain microvessel endothelial cells in culture, infected by C. ruminantium in the presence or absence of IFN-gamma. Infection induced the production of IL-1 beta, -6, and -8 mRNAs, and this effect was potentiated by IFN-gamma. A semi-quantitative PCR analysis indicated that similar amounts of IL-1 beta and IL-6 mRNAs were produced in response to C. ruminantium infection and to treatment with 30 to 40 ng/ml LPS. In addition, although IFN-gamma induced the synthesis of an MHC class II DQ alpha transcript (1.3 kb), an unusual transcript (1.5 kb) was induced by infection and not after LPS treatment. Infection did not affect MHC class I, class II DQ beta, and invariant chain mRNA levels. The present results suggest that C. ruminantium infection raises the immune activity of brain endothelial cells in vitro and that only part of this response can be attributed to LPS. One can hypothesize that cerebral endothelium in vivo efficiently contributes, by MHC Ag expression and production of ILs, to the activation and/or recruitment of leukocytes to the brain and thus plays an active role in the pathogenesis of cowdriosis and in the immune response to this pathogen.

Animals↗

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): diagnosis with fine-needle aspiration in a case with nodal and nasal involvement.

Sinus histiocytosis with massive lymphadenopathy (SHML) is a rare entity characterized by the proliferation of cells belonging to the macrophage-histiocyte family, but whose exact origin is unknown. A case of SHML occurring in a 62-yr-old female is described in which the diagnosis is initially suggested by fine-needle aspiration (FNA) of a cervical node. The smears show a background of lymphocytes and plasma cells and large histiocytes with well-preserved lymphocytes in their cytoplasm (emperipolesis or lymphophagocytosis). Both nodal and extranodal (nasal mass) involvement are confirmed by surgical biopsy. The immunohistochemistry suggests that SHML cells are functionally activated macrophages. Eight months after diagnosis, the patient is clinically well, with partial improvement of lymphadenopathy.

Biopsy, Needle↗

Nocturnal oxygen desaturation in diabetic patients with severe autonomic neuropathy.

The aim of the study was to assess whether diabetic patients with autonomic neuropathy suffer from arterial oxygen desaturation during sleep. Two groups of subjects were evaluated: group I consisted of 12 patients with cardiovascular autonomic neuropathy (five with insulin-dependent diabetes mellitus (IDDM) and seven with non-insulin-dependent diabetes mellitus (NIDDM)). Group II consisted of 8 healthy subjects. Age, percentage male and body mass index (BMI) were similar in both groups. Exclusion criteria were abnormalities in arterial gas measurements, chest X-ray, spirometry or the presence of cardiac arrhythmias, obesity, uremia, alcohol abuse and use of drugs other than insulin and oral hypoglicemic agents. The results of arterial oximetry when the subjects were awake showed no differences between the two groups. However, during sleep, diabetics with autonomic neuropathy had an increased number of desaturation episodes under 85% and those episodes were more prolonged. The results suggest that diabetics with autonomic neuropathy might have abnormal control of respiration that is apparent only during sleep.

Adult↗

Vaccination with yeast-expressed cottontail rabbit papillomavirus (CRPV) virus-like particles protects rabbits from CRPV-induced papilloma formation.

Papillomaviruses infect epithelia of the skin and mucous membranes and cause benign or malignant tumours in animals and in humans. The viruses are highly species-specific, and cell culture systems for propagating human papillomaviruses (HPVs) do not exist. However, there are several animal papillomavirus models. In the cottontail rabbit papillomavirus (CRPV) system, we demonstrated that recombinant CRPV virus-like particles (VLPs) consisting of the capsid proteins L1 or L1+L2 can be produced in the yeast Saccharomyces cerevisiae. Three immunizations with L1 VLPs formulated on aluminum adjuvant at 1-100 micrograms dose-1 efficiently protected rabbits from challenge with CRPV. Sera of immunized rabbits were shown to contain high-titered serum antibodies to CRPV L1 VLPs and to neutralize CRPV in vitro. Our results suggest that recombinant yeast-derived VLPs could be the basis for a candidate HPV vaccine.

Animals↗

Preclinical efficacy of a prototype DNA vaccine: enhanced protection against antigenic drift in influenza virus.

Vaccination with plasmid DNA expression vectors encoding foreign proteins elicits antibodies and cell-mediated immunity and protects against disease in animal models. We report a comparison of DNA vaccines, using contemporary human strains of virus, and clinically licensed (inactivated virus or subvirion) vaccines in preclinical animal models, to better predict their efficacy in humans. Influenza DNA vaccines elicited antibodies in both non-human primates and ferrets and protected ferrets against challenge with an antigenically distinct epidemic human influenza virus more effectively than the contemporary clinically licensed vaccine. These studies demonstrate that DNA vaccines may be more effective, particularly against different strains of virus, than inactivated virus or subvirion vaccines.

Animals↗

Tuberculosis among urban health care workers: a study using restriction fragment length polymorphism typing.

Cases of tuberculosis identified during 1992-1994 through an active tuberculosis surveillance network among six hospitals that serve New York City (the TBNetwork) were analyzed according to the occupational status of the patients. Clinical data were obtained by review of medical records, and restriction fragment length polymorphism (RFLP) typing of Mycobacterium tuberculosis isolates was performed. No known nosocomial outbreaks of tuberculosis occurred at these hospitals in the study period. Occupational status was known for 142 of 201 patients whose isolates were available for strain typing. Patients infected by organisms with a clustered strain typing pattern, as determined by RFLP analysis, were presumed to have recently acquired disease. RFLP typing revealed that isolates from 13 (65%) of 20 health care workers and 50 (41%) of 122 non-health care workers had a clustered RFLP pattern. The strains infecting eight (89%) of nine health care workers seropositive for human immunodeficiency virus (HIV) had a clustered RFLP pattern. Multivariate analysis of 75 patients with known HIV and occupational status revealed that HIV status (P = .03) and health care worker status (P = .02; RR = 2.77) were independent risk factors for a clustered RFLP strain. These findings suggest that many of the apparently sporadic cases of tuberculosis among health care workers may be due to unrecognized occupational transmission.

Adult↗

Use of a specific immunogenic region on the Cowdria ruminantium MAP1 protein in a serological assay.

Currently available serological tests for cowdriosis (Cowdria ruminantium infection) in domestic ruminants are hampered by their low specificities because of cross-reactivity with Ehrlichia spp. The use of recombinant major antigenic protein (MAP1) of C. ruminantium for serodiagnosis was investigated. Overlapping fragments of the MAP1 protein were expressed in Escherichia coli and were reacted with sera from sheep infected with either C. ruminantium or Ehrlichia ovina. Two immunogenic regions on the MAP1 protein, designated MAP1-A and MAP1-B, were identified. MAP1-A was reactive with C. ruminantium antisera, E. ovina antisera, and three MAP1-specific monoclonal antibodies, whereas MAP1-B reacted only with C. ruminantium antisera. An indirect enzyme-linked immunosorbent assay (ELISA) based on MAP1-B was further developed and validated with sera from animals experimentally infected with C. ruminantium or several Ehrlichia spp. Antibodies raised in sheep, cattle, and goats against nine isolates of C. ruminantium reacted with MAP1-B. Cross-reactivity with MAP1-B was limited to Ehrlichia canis and Ehrlichia chaffeensis, two rickettsias which do not infect ruminants. Antibodies to Ehrlichia spp. which do infect ruminants (E. bovis, E. ovina, and E. phagocytophila) did not react with MAP1-B. Antibody titers to C. ruminantium in sera from experimentally infected cattle, goats, and sheep were detectable for 50 to 200 days postinfection. Further validation of the recombinant MAP1-B-based ELISA was done with sera obtained from sheep raised in heartwater-free areas in Zimbabwe and from several Caribbean islands. A total of 159 of 169 samples which were considered to be false positive by immunoblotting or indirect ELISA did not react with MAP1-B. In conclusion, recombinant MAP1-B may be a suitable antigen for a sensitive serological test for cowdriosis, with dramatically improved specificity.

Animals↗

Coefficient of distribution of some organophosphorous pesticides in rat tissue.

Coefficient of distribution in tissue is proposed as an indicator of the affinity of xenobiotics for different tissues and their tendency to accumulate. The present study shows the distribution of some organophosphorous pesticides in rat tissues. Using the coefficient of distribution we established the preference of these insecticides for the various tissues. Each pesticide had a specific pattern of affinity for different tissues.

Adipose Tissue↗

Glycine elicits release of acetylcholine from the nucleus tractus solitarii in rat.

Previous studies have suggested that cardiovascular responses elicited by injection of glycine into the nucleus tractus solitarii (NTS) depend upon interactions between glycinergic and cholinergic neuronal elements in NTS. Release of acetylcholine in response to glycine is one such interaction that has been shown in slices of hippocampus and striatum. In this study we sought to test the hypothesis that glycine causes release of acetylcholine from neurotransmitter stores in NTS. We compared release from NTS with that from adjacent hypoglossal nucleus and from caudate nucleus. Release of radiolabeled acetylcholine was determined in vitro after incubating NTS with [3H]choline. Exposure of NTS and caudate nucleus, but not hypoglossal nucleus, to glycine caused release of acetylcholine in a calcium-dependent manner that varied with concentration of glycine in the incubation medium. The maximally effective concentration (1 mM) of glycine elicited 136% increases over basal levels. Glycine did not elicit release of [3H]acetylcholine from tissue when calcium ion had been removed from the bath. Acetylcholine also was not released if tissue was incubated with either strychnine (10 microM) or hemicholinium-3 (1 mM) prior to exposure to glycine (1 mM). Thus, glycine, acting at strychnine-sensitive receptors in NTS, elicits release of acetylcholine from a portion of locally synthesized neurotransmitter stores.

Acetylcholine↗

Protection of goats against heartwater acquired by immunisation with inactivated elementary bodies of Cowdria ruminantium.

In two experiments, four and five goats were vaccinated by giving two subcutaneous injections of a preparation of inactivated elementary bodies of Cowdria ruminantium (Gardel stock) mixed with Freund's adjuvant. All vaccinated animals together with four naive controls were challenged intravenously with 5 ml of supernatant of a culture of bovine endothelial cells infected with the same stock of Cowdria. All goats developed a high temperature. Two out of four, and four out of five vaccinated goats survived the challenge whereas all naive control animals died within 7-12 days. Vaccinated goats which died survived longer than the controls. No difference in antibody titres was observed between protected and non-protected vaccinated goats. Moreover, immune sera from surviving goats, whether heat inactivated or not, were unable to neutralize the infection of bovine endothelial cells by Cowdria in vitro. Mechanisms conferring protection on the immunized goats are unknown at the moment but the hypothesis that T-helper lymphocyte populations have been elicited seems to be likely. This method of immunization with dead organisms will help in the search for protective antigens against cowdriosis.

Animals↗

Treatment of adolescent sexual offenders: theory-based practice.

The treatment of adolescent sexual offenders (ASO) has its theoretical underpinnings in social learning theory. Although social learning theory has been frequently cited in literature, a comprehensive application of this theory, as applied to practice, has not been mapped out. The social learning and social cognitive theories of Bandura appear to be particularly relevant to the group treatment of this population. The application of these theories to practice, as demonstrated in a program model, is discussed as a means of demonstrating how theory-driven practice methods can be developed.

Adolescent↗

Targeted delivery of peptide epitopes to class I major histocompatibility molecules by a modified Pseudomonas exotoxin.

Cytotoxic T lymphocytes (CTLs) expressing the CD8 surface marker recognize peptides in association with major histocompatibility complex (MHC) class I molecules. Although most peptides expressed on MHC class I molecules are derived from self- or virally encoded proteins, delivery of exogenous proteins to the cytosol can result in their being processed for presentation to CTLs on MHC class I molecules. We describe two fusion proteins (PEMa and PENP), consisting of the binding and translocating domains of Pseudomonas exotoxin A (PE), fused to peptide epitopes from influenza A matrix protein and nucleoprotein, respectively. These fusion proteins were internalized and processed by MHC class I-positive target cells, resulting in sensitization of target cells for lysis by peptide-specific CTLs. A point mutation known to interfere with intoxication by wild-type PE also reduced the ability of PEMa to sensitize target cells. Fusion of peptide or polypeptide epitopes with PE provides a potential means of eliciting CTLs without the use of self-replicating agents, as well as a useful probe for studying MHC class I-restricted antigen processing.

ADP Ribose Transferases↗