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Biomedical subjects

R L Clancy

Publications and source records attributed to R L Clancy.

At least 145 records · Page 8Linked to original sources

Study of lymphocyte interaction in human mesenteric lymph nodes in vitro.

The immune function of lymphocytes isolated from human mesenteric lymph nodes (MLN) has been examined. Large yields of viable lymphocytes were obtained from MLN without the need for using enzyme or mucolytic agents. In comparison to gut mucosal lymphocytes, MLN lymphocytes (MLNL) were technically easier to manipulate and to use in providing a more quantitative analysis of T-B cell interaction. The results presented indicate that the pattern of immunoglobulin secretion and immunoregulation of lymphocytes isolated from MLN was similar to that in cells isolated from the lamina propria, supporting that MLN constitute an important component of gut-associated lymphoid tissue (GALT).

Antibodies, Bacterial↗

Antigen-specific response among T lymphocytes following intestinal administration of alloantigens.

The kinetics of T lymphocyte responses to mucosally presented antigen and the appearance of antigen-reactive T cells in mucosal and systemic tissues have been investigated by measuring secondary mixed lymphocyte culture reactivity after intestinal administration of alloantigens. The data indicate that T lymphocytes in the intestine are able to respond to mucosally presented alloantigens, and that following immunisation the T cell reactivity occurs first in Peyer's patches then sequentially in mesenteric lymph nodes, thoracic duct lymph, gut lamina propria and distant mucosal sites. The response was mucosally restricted and the ultimate location of antigen-reactive cells is influenced by site of antigen administration. Evidence is also presented for the existence of systemic nonreactivity to mucosally presented antigens.

Animals↗

Contribution of intraperitoneal immunization to the local immune response in the respiratory tract of sheep.

The contribution of gut-associated lymphoid tissue (GALT) to the local immune response in the respiratory mucosa of sheep has been investigated. Sheep were primed intraperitoneally (i.p.) with antigen in Freund's complete adjuvant, a procedure known to produce a large IgA-specific antibody-containing cell (ACC) response in intestinal lymph. ACC and their class specificity were then enumerated by double fluorochrome immunofluorescence in respiratory tissues after intratracheal (i.t.) antigen administration. This immunization procedure produced an enhanced IgA-specific ACC response in the upper respiratory tract mucosa compared with either i.t. or i.p. immunization alone and this was not reflected in the regional lymph nodes. Furthermore, chronic drainage of the intestinal efferent lymphatic duct for the duration of the immunization period abrogated the enhanced response in the respiratory mucosa. These data are consistent with the concept of an intermucosal cell circuit with respect to IgA cell precursors, and provide indirect evidence that IgA responses in the respiratory tract can be enhanced by harnessing the immune potential of GALT as a source of IgA precursors by appropriate immunization strategies.

Animals↗

Radioimmunoassay of human IgG, IgA and IgM.

Radioimmunoassay procedures for the quantitation of nanogram quantities of human immunoglobulin are described. The techniques have been successfully used to measure immunoglobulin secretion in culture supernatants by cultured human lymphocytes. Compared with previously published assays to assess lymphocyte function in vitro these procedures are simple, quick and reliable. A comparison of double-antibody and solid-phase radioimmunoassay is made. Similar sensitivity and variability in IgG and IgA assays were observed but it was not possible to develop a reliable double antibody radioimmunoassay for IgM. The solid-phase assay has several advantages over the double-antibody radioimmunoassays being quick to perform and using standard commercial reagents without necessity for exhaustive absorption.

Cells, Cultured↗

Specific immune response in the respiratory tract after administration of an oral polyvalent bacterial vaccine.

An oral killed polyvalent bacterial vaccine was assessed in a double-blind trial involving healthy volunteers. Three courses of oral vaccine were given over a 2-month period; each course contained 10(10) Haemophilus influenzae and 7 X 10(9) Staphylococcus aureus organisms. Immunity was assessed by monitoring antibody in saliva and serum over a 3-month period. No evidence of a nonspecific effect on immune parameters (immunoglobulin levels and Escherichia coli antibody) was detected in saliva or serum. An increase in H. influenzae antibody in saliva was detected in 55% of subjects receiving the vaccine compared with 6.7% of the placebo group. Antibody was associated with immunoglobulin A (IgA), IgG, and IgM, but the greatest increases over preimmunization levels were detected in the IgA class. No increase in serum antibody levels was detected. Subjects with higher preimmunization levels of salivary antibody to H. influenzae were less likely to respond to the oral bacterial vaccine. No increase in S. aureus antibody was detected in saliva or serum.

Administration, Oral↗

Role of adrenals on development of pressure-induced myocardial hypertrophy.

The effect of coarctation of the abdominal aorta (AC) and of sham operation (SO) on the development of myocardial hypertrophy was studied in three groups of male rats, i.e., a group without treatment prior to AC or SO (untreated), a group with bilateral adrenalectomy (ADX) 5-7 days before AC or SO, and a group in which the adrenal medulla was removed (MDX) 5-7 days before AC or SO. MDX resulted in functional elimination of the adrenal medulla without apparent effect on cortical function. The animals were killed 7-10 days after AC or SO. AC produced carotid blood pressure (CBP) increases of 33, 31, and 25 mmHg in the untreated, ADX, and MDX groups, respectively. Ventricular weight (HW), ventricular RNA concentration, and RNA-to-DNA ratio increased significantly after AC only in the untreated and MDX groups. In the ADX group, hypertension was followed by an increase in HW that could be detected only after normalization for body weight. It is concluded that absence of the adrenal gland significantly reduces the development of pressure-induced myocardial hypertrophy. Apparently, this is due to the absence of the adrenal cortex and not absence of the adrenal medulla.

Adrenal Glands↗

Behaviorally conditioned suppression of the immune response by antilymphocyte serum.

Previous studies have shown that cyclophosphamide, a drug with a broad spectrum of cytotoxic activity and one that produces noxious gastrointestinal side effects, can elicit taste aversion conditioning when paired with a non-immunosuppressive oral stimulus (saccharin) resulting in immunosuppression after subsequent exposure to the paired stimulus (1). The study reported here indicates that rabbit anti-rat lymphocyte serum (ALS) which is selectively cytotoxic for lymphocytes and does not produce sensory side effects can similarly induce taste aversion conditioning of the immune response. Rats were exposed to oral saccharin paired with ALS injection. Upon subsequent reexposure to saccharin alone the immunosuppressive effects of ALS were reenlisted and the primary mixed lymphocyte culture response of conditioned rats to allogeneic lymphocytes was suppressed by 35% compared to controls. The demonstrated influence of psychologic factors on the immune response has far reaching implications, especially to human medicine, and their role in the course of disease and recovery in man demands further investigation.

Animals↗

Specificity of plasmapheresis in the treatment of chronic relapsing polyneuropathy.

A 27-year-old woman with an eight year history of chronic relapsing polyneuropathy presented in her fifth relapse. Raised immune complexes prompted a trial of plasmapheresis. Remarkable clinical improvement was seen after the second exchange. Complete remission was obtained after ten treatments. Subsequently, further relapses have occurred, each responsive to plasmapheresis. The effect of plasma exchange in this patient appears to be unique as neither charcoal perfusion nor plasma infusion per se proved efficacious. The patient is currently maintained with weekly plasma exchanges, her course complicated by supervening hepatitis B antigenemia. The clearance of immune complexes observed during plasmapheresis raises the possibility that removal of a serum factor is responsible for her clinical improvement and that patients with such a factor may benefit from plasmapheresis.

Adult↗

Ontogeny of the secretory immune system in man.

Immunoglobulin and albumin concentrations and Escherichia coli antibody levels were determined in a prospective study of saliva taken from 63 healthy infants during the first year of life. Albumin and IgG were present in high concentrations at birth (57 +/- 6 and 35 +/- 8 mg/l respectively) and decreased in parallel to low values at two months of age. IgA was detected by three weeks of age. The IgA concentration fluctuated until six months of age, after which constant values were observed (14 +/- 3 mg/l). Low levels of salivary IgM (2.4 +/- 1.2 mg/l) were demonstrated in 37% of infants at four weeks of age. No E. coli antibody was detected. There was no significant difference between breast-fed and formula-fed infants. These findings suggest: (i) that mucosal membrane permeability is not restricted to the gut; (ii) that changes in mucosal permeability are non specific and not restricted to the uptake of specific food protein or ingestion of maternal milk; (iii) maternal IgG may contribute to mucosal defence in the neonate; (iv) fluctuations in the concentration of IgA may reflect a balance between intense antigenic stimulation in the gut in the first weeks of life and immune regulatory mechanisms and (v) ingestion of maternal milk does not modify the pattern of ontogeny.

Albumins↗

Early pregnancy factor as a monitor for fertilization in women wearing intrauterine devices.

Measurement of early pregnancy factor (EPF) by the rosette inhibition test was performed on serum samples from 14 women using intrauterine devices (IUDs). Serial blood samples taken during the luteal phase of 23 cycles demonstrated in six of the cycles a transient appearance of EPF during the 6- to 8-day period following ovulation. In contrast, no EPF activity was found in sera obtained from women in whom fertilization was prevented, either by sexual abstinence or tubal ligation. These observations support the postulate that the IUD functions by the prevention of implantation of the fertilized ovum, rather than by preventing fertilization.

Adult↗

Validation of the rosette inhibition test for the detection of early pregnancy in women.

The authors validated use of the rosette inhibition test for the detection of early pregnancy factor (EPF) in human pregnancy, first by optimizing conditions for the assay, using known pregnant and nonpregnant sera, and second, by examining the performance of this assay in three clinical situations: a "blind" study involving coded first-trimester sera showed 80% correlation with pregnancy status; serial assay of EPF activity in sera collected from normal women attempting to conceive, correlated with human chorionic gonadotropin beta-subunit (beta-hCG) levels and pregnancy status; a longitudinal study of serial serum samples through two normal pregnancies showing the continued presence of EPF until the early third trimester in each case. It was concluded that with the rosette inhibition assay, consistent demonstration of a pregnancy-associated substance (EPF) could be obtained.

Chaperonin 10↗

Fertilization and early pregnancy loss in healthy women attempting conception.

The rosette inhibition test was used to monitor the activity of an early pregnancy factor (EPF) in sera collected from 18 healthy women who were attempting to conceive. Serial blood samples collected during the luteal phase of 21 menstrual cycles demonstrated the appearance of EPF in 14 of the cycles, of which six showed only transient EPF activity over a 5-10 day period following ovulation. These results indicate a 67% rate of fertilization and a 36% rate of early conceptus losses.

Abortion, Spontaneous↗

Detection of an immunosuppressive factor in human preimplantation embryo cultures.

Within 48 hours of fertilization of human preovulatory oocytes in vitro, an immunosuppressive factor was detected in the culture medium by a rosette inhibition test. Cultures in which fertilization of the oocyte was unsuccessful were indistinguishable from control medium. Release of an early pregnancy factor from the preimplantation embryo could be of clinical significance to the establishment of pregnancy after embryo transfer.

Chaperonin 10↗

Early pregnancy factor: its role in mammalian reproduction--research review.

An immunosuppressive early pregnancy factor associated with mammalian reproduction is currently attracting considerable interest. Research into its detection, site of production, distribution, immunosuppressive property, characterization, and application is in progress in a number of laboratories. This review aims to crystallize the current research findings and to identify significant areas for further investigation and application.

Animal Husbandry↗

Slow-reacting substance from alveolar macrophages--a mechanism of asthma?

The effects of alveolar macrophages on bronchial reactivity were studied in vitro to determine whether these cells could provide a pathogenetic link between cellular components of the inflammatory response, chemical medication of smooth muscle contraction and possible local mechanism of asthma. Alveolar macrophages harvested from rabbit lungs produced consistent and prolonged contractile responses in guinea-pig tracheal rings. The contractile material had the pharmacological and physical properties of slow-reacting substance (SRS) and, in particular, it was completely antagonized by minute concentrations (5 ng/ml) of a specific SRS antagonist, FPL 55712. The average contractile response per 10(6) macrophages was quantitatively equivalent to that produced by 76 ng methacholine. These findings not only support the view that local mechanisms may be of relevance in the pathogenesis of asthma, but could also have possible implications for therapy.

Animals↗

Myocardial intracellular pH regulation during chloride depletion.

The possible role of a HCO-3/Cl- transmembrane exchange as a mechanism of alkalinization in the myocardial cell was studied in isolated rabbit hearts perfused with Ringer solution. Cl- depletion was produced by replacing Cl- of the perfusate by SO2(-4) or glucuronate. Intracellular pH (pHi) was calculated both in Cl--free and Cl--containing hearts from the distribution of 14C-labeled 5',5'-dimethyloxazolidine-2,4-dione. Acid-base alterations were produced by changing perfusate HCO-3 concentration and/or CO2 partial pressure (PCO2). Depletion of Cl- resulted in an increase in pHi for any given level of extracellular pH. Increasing PCO2 at constant perfusate HCO-3 resulted in changes in pHi and cell HCO-3 (HCO-3i) that were similar in both Cl--free and Cl--containing hearts. Increasing perfusate HCO-3 at constant PCO2 resulted in increases in pHi and HCO-3i in both Cl--free and Cl--containing preparations. When the increases in HCO-3i secondary to an increase in extracellular HCO-3 were plotted as a function of the initial HCO-3i, a significant negative correlation was observed, suggesting that the elevation of HCO-3i was influenced by the initial HCo-3i and not by the presence or absence of Cl-. It is concluded that even though HCO-3 may enter the myocardial cells in exchange for Cl- during Cl-depletion, lack of Cl- does not alter the ability of the myocardial cell to regulate its pHi. This argues against a HCO-3/Cl- exchange as a mechanism of regulation of myocardial pHi.

Acid-Base Equilibrium↗