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Biomedical subjects

P Billings

Publications and source records attributed to P Billings.

At least 19 recordsLinked to original sources

Connection between the inner ear and the lymphatic system.

OBJECTIVE: The aim of this study was to identify the lymphatic drainage of the inner ear in guinea pigs. STUDY DESIGN: Prospective study. METHODS: The prospective study was performed in guinea pigs by injection of keyhole limpet hemocyanin (KLH) into either the right-side scala tympani or the middle ear cavity. The left side was not injected and served as a control. Fifteen minutes after injection, the animals were killed by intracardiac perfusion with paraformaldehyde and tissue specimens (right and left temporal bones, cervical lymph nodes, and the spleen) were collected. The presence of KLH in each specimen was determined by immunohistochemical assay of frozen sections using polyclonal mouse anti-KLH antibodies. RESULTS: After injection into the middle ear, labeled cells were identified in the parotid, superficial ventral, mandibular, and deep cranial cervical lymph nodes. However, after inner ear injections KLH was present in only the parotid and superficial ventral cervical nodes. The spleen contained KLH-positive cells following injection into either the middle or inner ear, but not all animals contained labeled spleen cells. CONCLUSIONS: The inner ear has a connection to the lymphatic drainage system. Because fewer lymph nodes contained labeled cells after inner ear injection than after middle ear injection, it is concluded that the inner ear does not simply drain to the middle ear and subsequently to the lymph nodes but seems likely to have its own connections.

Animals↗

Characterization of an experimentally induced inner ear immune response.

OBJECTIVE: To determine the effects of a sterile immune response on the structure and function of the cochlea. METHODS: An immune response was created in guinea pigs by systemically sensitizing the animals to keyhole limpet hemocyanin and subsequently challenging the inner ear with the protein. Animals were allowed to survive for 1 to 5 weeks, after which the cochlea was evaluated histologically. Hearing was measured by auditory brainstem response before the inner ear challenge, during the survival period, and prior to sacrifice. RESULTS: Inflammatory cells infiltrated the cochlea from the circulation. Surface preparations and plastic sections of the organ of Corti 1 and 2 weeks after the initiation of the inflammation demonstrated degeneration of the sensory and supporting cells in cochlear turns containing inflammatory cells. Good preservation of structures was seen in the more apical cochlear turns with little or no inflammatory cells. In cochleas from animals that survived 5 weeks, most of the infiltrated cells were cleared after undergoing apoptosis and the inflammatory matrix in the scala tympani began to calcify. Hearing loss was moderate to severe depending on the amount of inflammation. CONCLUSION: Although in general the immune response serves to protect an organism from infection, these results demonstrate that bystander injury associated with local immune responses in the cochlea, an organ incapable of regeneration, causes permanent cochlear destruction and hearing loss.

Adjuvants, Immunologic↗

Addressing the needs of underserved populations: one organization's experience.

Dental decay is the most prevalent and preventable chronic disease of childhood. Underserved populations are at a health disadvantage with greater unmet needs. This article will discuss the components of oral health promotion programs and facilities designed to meet the needs of underserved populations. These components include organization, needs assessment, resource assessment, priority-setting and planning, oral health intervention, and monitoring and evaluation. Examples from the experience of the San Diego Children's Dental Health Association will be presented in the discussion of each component.

California↗

Genetic testing in the workplace: a view from the USA.

Progress in human genetics, accelerated by the Human Genome Project, is leading to a rapid proliferation in the number of genetic tests. Although they have their benefits, genetic tests have in the past been used by various societal institutions, including employers, to discriminate against and stigmatize individuals. In the light of the increase in the number of tests and some current reports of discrimination in employment, a variety of legal and regulatory measures have been proposed to prevent genetic discrimination in the workplace.

Genetic Diseases, Inborn↗

Effects of various doses of latamoxef (moxalactam) on haemostasis.

The effects of intravenous latamoxef therapy at two doses of 3g and 6g daily for 7 days was assessed by various haemostatic parameters. With both doses, the prothrombin time, thrombin time and activated partial thromboplastin time remained within the normal range throughout the study. However, with the 6g day-1 dose there was a marked prolongation of the bleeding time associated with defective platelet aggregation to adenosine diphosphate and low dose collagen after 7 days therapy. With the 3g day-1 dose of latamoxef, there was no prolongation of the bleeding time and only minor changes in platelet aggregation responses.

Bleeding Time↗

Inhibition of oral carcinogenesis by a protease inhibitor.

The effect of the Bowman-Birk inhibitor (BBI) and soybean trypsin inhibitor (SBTI) on experimental 7,12-dimethylbenz[a]anthracene [(DMBA) CAS: 57-97-6]-induced oral carcinogenesis in Syrian male hamsters was examined. All treatments were applied topically on both cheek pouches for 20 weeks, and the animals were then sacrificed. Gross and microscopic evaluations revealed a statistically significant reduction in the number of invasive carcinomas, the total number of tumors, and the tumor mass for the DMBA + BBI treatment group compared to animals treated with DMBA alone, DMBA and autoclaved BBI (a preparation in which protease inhibitor activity is destroyed), or DMBA + SBTI. A protease activity (with the use of Boc-Val-Pro-Arg-MCA as substrate) was measured and found to be elevated about tenfold in tumorous and nontumorous tissue from DMBA-treated cheek pouches. This protease activity was found to be decreased in the DMBA and BBI treatment group but not in the DMBA + SBTI or DMBA and autoclaved BBI treatment groups, as compared to the protease activity in the DMBA treatment group. Partial characterization of the Boc-Val-Pro-Arg-MCA hydrolyzing activity with diisopropyl fluorophosphate suggests that the proteolytic activity is a serine protease. Iodoacetamide and diethyl pyrocarbonate also inhibit enzyme activity, suggesting that other residues may be necessary for catalysis, possibly including cysteine and histidine. Our results suggest that this protease activity may play a role in DMBA-induced cheek pouch carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

Genetic control of cytolytic T lymphocyte responses. III. The role of K and I region alleles on the specificity of the cytolytic T lymphocyte response to trinitrophenyl-modified syngeneic cells.

It has previously been demonstrated that genes in the H-2K and/or I-A region control the specificity of the cytolytic T lymphocyte (CTL) response to trinitrophenyl-(TNP) modified syngeneic cells. Strains of mice bearing the k allele in the K and/or IA region do not exhibit cross-reactive lysis of TNP-modified allogeneic targets after stimulation with TNP-modified syngeneic targets. In this report we present evidence for independent roles of genes in the H-2K and I-A regions on the control of CTL specificity. One gene, mapping in the H-2K region, is expressed on the stimulator cell population, whereas the other gene maps to the I region and is expressed in the population of responding cells and need not be expressed in the stimulator cell population. Thus, we suggest that Ir genes localized to the I region may influence the response for prekiller cells to H-2K/D gene products.

Alleles↗

HnRNP core proteins: synthesis, turnover and intracellular distribution.

Our present data indicate that the Mr 34-40,000 polypeptides which are involved in the binding of a large fraction of hnRNA sequences, including mRNA, are for the most part metabolically stable species in mouse ascites tumor cells. An exception to this generalization is the smallest of 30S RNP core polypeptides, the Mr 34,000 protein, which has a relatively high turnover rate. The relationship of the various synthesis and degradation rates to the physiological state of mammalian cells remains to be determined, as does the pathway of assembly and disassembly of RNP substructures during re-utilization of the proteins and during their turnover. Immunofluorescent studies, which have confirmed the expected nucleoplasmic or euchromatic localization of the RNP core proteins, have also indicated that these species are stable during mitosis, at which time they are dispersed through the cell away from the condensed chromosomes. The proteins appear to relocate in the nucleus as soon as the nuclear envelope is reformed.

Animals↗

Genetic control of cytolytic T-lymphocyte responses. I. Ir gene control of the specificity of cytolytic T-lymphocyte responses to trinitrophenyl-modified syngeneic cells.

The ability of cytotoxic T lymphocytes (CTL) induced in vitro to trinitrophenyl (TNP)-modified syngeneic cells to cross-reactively lyse a TNP allogeneic spleen target varies among inbred mouse strains. The cross-reactive CTL phenotype was found to be histocompatibility 2 (H-2) linked and to be dominant in F1 hybrid mice. All strains investigated demonstrated cross-reactivity except for some strains bearing portions of the H-2k haplotype. The gene(s) controlling this response maps to the K and/or I-A region of the H-2 complex. We have termed the immune response (Ir) gene responsible for controlling the specificity of CTL induced to TNP-modified syngeneic cells Ir-X-TNP.

Animals↗

Genetic control of cytolytic t-lymphocyte responses. II. The role of the host genotype in parental leads to F1 radiation chimeras in the control of the specificity of cytolytic T-lymphocyte responses to trinitrophenyl-modified syngeneic cells.

Bone marrow cells from C3H (H-2k) mice, a strain that does not exhibit cross-reactive lysis of trinitrophenyl (TNP)-modified allogeneic targets, were allowed to mature in heavily irradiated (B6 times C3H)F1 (H-2b/k) recipients, an F1 hybrid that does demonstrate cross-reactive lysis. Spleen cells from these chimeric mice were removed after 3-4 mo and by H-2 typing shown to be of C3H origin. These cells were found to be tolerant to B6 alloantigens by mixed lymphocyte reaction and cell-mediated cytotoxicity and, when stimulated in vitro with TNP-modified syngeneic cells, now cross-reactively lysed TNP-modified allogeneic targets. These studies demonstrate that the host environment where T cells differentiate influences the specificity of the primary cytolytic T-lymphocyte (CTL) response to TNP-modified syngeneic antigens.

Animals↗