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Biomedical subjects

R D Peterson

Publications and source records attributed to R D Peterson.

At least 19 recordsLinked to original sources

Two- and three-dimensional HCN experiments for correlating base and sugar resonances in 15N,13C-labeled RNA oligonucleotides.

New 2D and 3D 1H-13C-15N triple resonance experiments are presented which allow unambiguous assignments of intranucleotide H1'-H8(H6) connectivities in 13C- and 15N-labeled RNA oligonucleotides. Two slightly different experiments employing double INEPT forward and back coherence transfers are optimized to obtain the H1'-C1'-N9/N1 and H8/H6-C8/C6-N9/N1 connectivities, respectively. The correlation of H1' protons to glycosidic nitrogens N9/N1 is obtained in a nonselective fashion. To correlate H8/H6 with their respective glycosidic nitrogens, selective 13C-refocusing and 15N-inversion pulses are applied to optimize the magnetization transfers along the desired pathway. The approach employs the heteronuclear one-bond spin-spin interactions and allows the 2D 1H-15N and 3D 1H-13C-15N chemical shift correlation of nuclei along and adjacent to the glycosidic bond. Since the intranucleotide correlations obtained are based exclusively on through-bond scalar interactions, these experiments resolve the ambiguity of intra- and internucleotide H1'-H8(H6) assignments obtained from the 2D NOESY spectra. These experiments are applied to a 30-base RNA oligonucleotide which contains the binding site for Rev protein from HIV.

Base Sequence

Expression of aminopeptidase N in fetal rat lung during development.

The ectopeptidase, aminopeptidase N, serves as a cell surface marker of the apical surface of the alveolar type II epithelial cell in adult lung. It is also present in fetal lung before differentiation of morphologically mature type II alveolar epithelial cells, suggesting that it is expressed by precursors of the type II cells. We have examined the mRNA coding for the aminopeptidase in adult and fetal lung and in mature type II cells and determined levels of mRNA and immunoreactive protein during fetal lung development. Comparison of the temporal patterns of steady-state levels of aminopeptidase mRNA and immunoreactive protein during development show that the expression of the protein is developmentally regulated and that expression is regulated, at least in part, at a pretranslational level. Both mRNA and immunoreactive protein levels increase severalfold on the final gestational day, suggesting that the function of the aminopeptidase may be associated with air breathing.

Aging

Maternal-fetal HLA-DR relationships and pregnancy-induced hypertension.

OBJECTIVE: Some studies have found an increased prevalence of pregnancy-induced hypertension among women sharing HLA antigens with their spouses or fetuses, thus supporting the hypothesis that maternal sensitization to fetal HLA alloantigens reduces the risk for pregnancy-induced hypertension. However, not all studies have confirmed these findings. No investigators have examined the four different types of maternal-fetal HLA relationships in their studies of pregnancy-induced hypertension. Our goal was to examine such associations to test further the HLA-allosensitization hypothesis. METHODS: We conducted a cohort study of pregnancy-induced hypertension among 683 nulliparous women. Women and their neonates were typed for HLA-A, -B, -DR, and -DQ antigens using serologic techniques to establish maternal-fetal relationships. RESULTS: We found an increased prevalence of pregnancy-induced hypertension when the fetus, but not the mother, was potentially exposed to HLA-DR alloantigens (maternal allogenicity) compared with the other three conditions combined (P < .003). Controlling for confounding factors, the increased prevalence of pregnancy-induced hypertension persisted in situations of maternal HLA-DR allogenicity (P < .007). CONCLUSIONS: Based upon our observations and other immunologic studies of pregnancy-induced hypertensive and uncomplicated pregnancies, we conclude that a maternal humoral response against fetal anti-HLA-DR immunoglobulin (IgG) antibody may influence the development of pregnancy-induced hypertension. This could occur when an immunocompetent fetus is exposed to maternal HLA-DR alloantigens, maternal exposure to fetal HLA-DR alloantigens alloantigens, maternal exposure to fetal HLA-DR alloantigens is not possible, and fetal IgG antibody bears paternally inherited markers allogeneic to the mother.

Eclampsia

In vitro lymphocyte activity in women with endometriosis--an altered immune response?

OBJECTIVE: To determine the possible role of the immune system in the pathogenesis of endometriosis. DESIGN: The lymphocyte proliferative response in the presence of autologous endometrial cells was assayed by tritiated thymidine incorporation. SETTING: Patients were recruited from a university outpatient clinic. MAIN OUTCOME MEASURE: To determine the lymphocyte proliferative response to endometrium in controls and patients with endometriosis. PARTICIPANTS: Twenty patients with endometriosis and 26 control women were studied. RESULTS: The lymphocyte proliferative response in the presence of autologous endometrium was significantly lower in women with endometriosis when compared with controls. CONCLUSION: This study indicates that an altered lymphocyte/endometrial cell relationship is operational in women with endometriosis and may contribute to the pathogenesis of the disease.

Adult

Cancer susceptibility in ataxia-telangiectasia.

Ataxia-telangiectasia (A-T) is a syndrome that has an extremely high incidence of cancer. Patients with the disease are homozygous for a mutant gene, the A-T gene, located at 11q23. Of these individuals, 30-40% develop cancer. Of these cancers, 80% are lymphoid. Those heterozygous for the A-T gene also have an increased frequency of cancer, the most notable being the 6.8-fold increase of breast cancer in females carriers. The syndrome is characterized cytogenetically by increased nonrandom chromosome breaks and rearrangements in lymphocytes involving the sites of the immunoglobulin and T-cell receptor genes. Clones of cells having the same rearrangements are often present in the blood of the A-T patients and if the rearrangements involve certain sites, especially a locus within 14q32, the propensity to progress to a malignant transformation is great. Sequencing the A-T gene and ascertaining its function should contribute significantly to our understanding of the molecular mechanisms underlying cancer susceptibility.

Ataxia Telangiectasia

Contact lens wear with the USAF Protective Integrated Hood/Mask chemical defense ensemble.

The Protective Integrated Hood/Mask (PIHM) chemical defense aircrew ensemble blows air from the mask's plenum across the visor at a rate of approximately 15 L/min in order to prevent fogging of the visor and to cool the aircrew member's face. This study was designed to determine the effect of the PIHM airflow on soft contact lens (SCL) dehydration, contact lens comfort, and corneal integrity. There were 26 subjects who participated in this study: 15 SCL wearers, 6 rigid gas-permeable (RGP) wearers, and 5 nonspectacle wearing controls. Contrast acuity with the 3 Regan charts, subjective comfort, and relative humidity (RH) and temperature readings under the PIHM mask were monitored every 0.5 h during 6-h laboratory rides. Slit-lamp examinations and SCL water content measurements with a hand-held Abbe refractometer were made before and after the rides. High RH under the mask may have accounted for the moderate SCL dehydration (8.3%), no decrease in contrast acuity for any group, and lack of corneal stress. Although all groups experienced some inferior, epithelial, punctate keratopathy, RGP wearers had the most significant. SCLs performed relatively well in the PIHM mask environment. Testing with other parameter designs is necessary before recommending RGPs with the PIHM system.

Aerospace Medicine

Effect of method of administration of psyllium on glycemic response and carbohydrate digestibility.

To determine whether there was any advantage to taking a soluble fiber supplement separate from food, as opposed to incorporated into a food, we used psyllium as a model, either taken in water just before a flaked bran cereal test meal, sprinkled on top of the cereal, or actually incorporated into the flake. In normal subjects, psyllium reduced the glycemic response when sprinkled onto or incorporated into the cereal, but not when taken before the cereal. Varying the amount of psyllium incorporated into the cereal from 0 to 20% resulted in a linear dose-dependent reduction of the glycemic index (GI) (GI = 101 -2.2 x % psyllium; r = 0.950; p less than 0.002). In subjects with diabetes, the blood-glucose-lowering effect of the psyllium flake cereal was similar to that in normal subjects. Mixing psyllium with the cereal or incorporating it into the cereal reduced the rate of digestion of bran flakes in vitro but was not associated with increased breath hydrogen levels in vivo as an index of rapid colonic fermentation. The bran flakes with psyllium incorporated was rated as no less palatable than the bran flakes cereal alone, and significantly more palatable (p less than 0.05) than taking psyllium in water before the cereal or sprinkling psyllium onto the cereal. These studies confirm earlier reports that viscous fibers must be intimately mixed with the food to have the effect of reducing blood glucose responses, and that the mechanism of action relates to a reduced rate of digestion rather than carbohydrate malabsorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Chorionic structure of the egg of the screwworm, Cochliomyia hominivorax (Diptera: Calliphoridae).

The chorion of the Cochliomyia hominivorax (Coquerel) egg is described using observations from scanning and transmission electron microscopy and light microscopy. Included are the gross structure and surface characteristics of the chorion, the basic architecture and internal components of the chorion proper, the location and function of the hatch lines, and the functional morphology of the plastron region as a respiratory structure. In the regular hexagonal arrangement and form of individual structural units, the chorion of the screwworm egg exhibits basic architectural features common to other higher Diptera. Within the open spaces of the endochorionic layer, however, are previously undescribed membranous structures of unknown function which appear to line the cavities of the endochorion. The plastron region partially encircles the micropyle (anterior end) of the egg and extends along the dorsal surface to the posterior pole; it is delineated laterally by the hatch lines. The chorion ruptures along the anterior region of the hatch lines as the larva emerges. The plastron region is composed of elaborate stalked aeropyles above a highly dissected inner reticulum. This structure is believed to function as a respiratory organ when the egg is immersed in fluid.

Animals

p146 type II alveolar epithelial cell antigen is identical to aminopeptidase N.

A prominent membrane protein of rat type II alveolar cells, p146, was originally identified by one of many mouse monoclonal antibodies that were produced to rat lung cells in the course of a search for differentiation antigens that might prove useful in studying lung differentiation. We report here results from analysis of the primary structure of this molecule and, based on this knowledge, the elucidation of the function of the protein. Amino acid sequencing of the NH2-terminal portion of the p146 protein, plus partial sequencing of several peptides obtained by limited proteolysis, indicates it is identical to aminopeptidase N. Further, the immunoaffinity purified p146 protein has aminopeptidase N activity. The discussion includes references to other molecules such as CD 13 and CD 10 (CALLA) that were recognized as differentiation antigens and subsequently found to be peptidases. The possible biological implications of such a peptidase on the luminal surface of type II alveolar cells are also considered.

Amino Acid Sequence

Ectopeptidases of alveolar epithelium: candidates for roles in alveolar regulatory mechanisms.

This commentary discusses the implications of recent observations indicating that at least one, and probably three, ectopeptidases are exhibited on the surface of alveolar epithelial cells. The unique biological feature of the ectopeptidases is that they are expressed on the surface of only selected cell types and at specific stages in the differentiation of those cells. Consequently they are positioned to exert their enzymatic activity in a very restricted locale. Drawing from information derived from studies of this activity on other cells, we develop the proposition that the ectopeptidases on alveolar epithelial cells regulate the biological activity of peptides encountered at this site. These may be peptides produced by the alveolar epithelial cells or cytokines that have the potential of influencing the alveolar cells. Awareness that these ectopeptidases are expressed on the luminal surface of these cells thus opens heretofore unrecognized avenues of investigation.

Animals

Signs of cellular immunosuppression correlate with HLA-DR phenotypes in healthy HIV-negative homosexuals: preliminary findings.

Twelve healthy, anal-receptive, homosexual Caucasian males who were seronegative for HIV antibody were typed for HLA-DR antigens. Flow cytometry was used to immunophenotype peripheral blood lymphocytes bearing the CD4, CD8, LEU7, and combined CD8 and LEU7 antigens. These individuals had reported a large number of sexual partners within a five-year period preceding this study. Each individual was assigned a score based on the Hardy-Weinberg frequency of their HLA-DR phenotype in the Caucasian population. The larger the value of this score, the more common the HLA-DR phenotype, the smaller the score, the rarer the phenotype in the population at large. A significant inverse correlation was observed between this score and the proportion of lymphocytes with CD8 and LEU7 antigens. Lymphocytes bearing these two antigens have in vitro suppressor activity and are elevated in patients with human immunodeficiency virus (HIV) infection. The inverse association between CD8+/LEU7+ cells and frequency of HLA-DR phenotypes is consistent with the hypothesis that individuals with rarer phenotypes whose partners are drawn from the population at large are more likely to be challenged during anal insemination, which results in immunosuppression (alloantigenic challenge hypothesis). On the other hand, it is possible that an association exists between certain HLA-DR phenotypes and immune status. Although these observations were made in a very small sample, we believe that the strength of this association provides justification for further investigation into the possibility that alloantigenic challenge may increase the risk for infection, if exposed to HIV, and augment the immunosuppressive action of HIV once significant infection has occurred.

Antigens, Differentiation

A newly identified iron binding protein in duodenal mucosa of rats. Purification and characterization of mobilferrin.

An iron binding protein with an approximate molecular mass of 56,000 daltons was purified to homogeneity from homogenates of rat duodenal mucosa. The protein was biochemically and immunologically distinct from transferrin and ferritin and competitively bound cobalt, copper, zinc, and lead. Each molecule bound one molecule of iron with a Kd of 9 X 10(-5). Dissociation of iron and the protein was accelerated at acid pH. Using an immunogold method, the protein was identified in the apical cytoplasm of proximal small intestinal cells and was not observed elsewhere in the intestinal mucosa and in other body organs. It was named mobilferrin from its city of origin and to differentiate it from other previously identified iron binding proteins.

Amino Acids

Dental health status and treatment needs of elderly residents of Edmonton, Alberta.

The oral health of 140 independent elderly volunteers, selected from different sections of Edmonton, Alberta, was assessed in conjunction with their nutritional and medical status, in an attempt to evaluate the dental needs of this population. Dental caries was assessed using WHO standards and the CPITN was used in assessing periodontal and gingival health needs. The mean age of the participants was 70.9 +/- 2.6 years. The average time since they had last seen a dentist was 3.0 +/- 6.2 years. Twenty-six percent of the group were edentulous and wore full dentures. An evaluation of denture hygiene and retention showed that 53 per cent of all maxillary and 57 per cent of all mandibular appliances exhibited poor hygiene; 33 per cent and 54 per cent, respectively, had problems with retention and/or occlusion. Only 12 per cent of the group exhibited any sort of mucosal pathology, all of which was related to ill fitting dentures. The total population had a mean of 15.0 +/- 11.1 teeth, only 0.5 of these were decayed, while 8.9 were restored. CPITN scores taken from a total of 511 sextants with standing teeth showed that 16 per cent of the group exhibited bleeding upon probing, 29 per cent had calculus, 13 per cent exhibited pocketing, while 3.6 per cent had deep pockets. Sixty-seven per cent of the population required dental treatment, none of whom needed emergency intervention. Over 49 per cent of the dentate population could benefit from prophylaxis; 16 per cent required more definitive periodontal treatment. Forty-five per cent of the denture population required treatment.

Aged

In vitro effects of complement inactivation upon burn-associated cell-mediated immunosuppression.

Serum of severely burned patients possesses in vitro capacity to suppress cell-mediated immunologic responses. Failure to establish immune competence is predictive of mortality, usually from sepsis. In this investigation, the hypothesis that complement fragments, known to be elevated in the acute phases of burn injury, contribute to this suppression is tested. Serum taken from patients with massive (greater than 60%) and major (less than or equal to 60%) burn injury was analyzed for the ability to suppress mitogen-induced lymphocyte blastogenesis before and after exposure of the burn serum to (complement inactivating) temperatures. All patients in this study had immune suppressive serum. Heat inactivation partially restored immune competence in the serum of all patients, though significantly more so in patients with major burns compared with those with massive burns. Complement appears to play a contributory role in the acute stages of burn-induced, cell-mediated immunosuppression, though its role in patients with massive burn injury is overshadowed by the presence of serologic suppressive factors not present (or present in lower concentration) in patients with major burns.

Adult

Does exposure to HLA alloantigens trigger immunoregulatory mechanisms operative in both pregnancy and AIDS?

The complex biological processes responsible for regulating the immune system are presently the subject of considerable interest and study. New insight into this process comes from a variety of observations and it is the purpose of this communication to develop the hypothesis that two seemingly quite disparate observations point to a common biological mechanism bearing on immunoregulation. The observations concern the unique immunologic relationship between mother and fetus and the immunoregulatory abnormalities encountered in HIV-induced acquired immunodeficiency syndrome (AIDS). Exposure to foreign (allo) major histocompatibility complex (MHC) antigens can potentially occur during pregnancy, the transfusion of blood or blood products, or anal insemination. The hypothesis, in its simplest form, states that such MHC alloantigenic exposure triggers a sequence of immunoregulatory mechanisms resulting in immunosuppression and that this response has evolved in placental mammals as a means of protecting the fetus from maternal immune rejection and promoting optimal fetal development.

Acquired Immunodeficiency Syndrome

Speculations on ataxia-telangiectasia: defective regulation of the immunoglobulin gene superfamily.

In this short article, Raymond Peterson and Jane Funkhouser develop the argument that the common molecular mechanism linking the various clinical manifestations of ataxia-telangiectasia (AT) is a defect in the regulation of the immunoglobulin (Ig) gene superfamily. They propose that the AT gene codes for a protein essential for the orderly expression of this gene family, perhaps regulating the gene rearrangement process that appears to be a unique characteristic of this system. Members of the Ig gene superfamily play a major role in the development and operation of the immune and nervous systems, and any perturbation of their expression would be anticipated to produce a panoply of signs and symptoms, such as those characterizing the AT phenotype.

Ataxia Telangiectasia