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Biomedical subjects

R L Clancy

Publications and source records attributed to R L Clancy.

At least 127 records · Page 7Linked to original sources
PubMed1987

Induction of antigen-reactive and IL-2 receptor bearing cells following oral immunization in humans.

A human model of oral immunization using two forms of HI antigen preparation was studied. Oral immunization with killed HI (monobacterial) or HI in a polybacterial mix (polybacterial) induced an enhanced antigen-driven proliferative response in circulating PBL of normal subjects as well as an increase in the precursor frequency of HI antigen-specific cells using limiting dilution analysis. However, the proliferative response was better maintained at a high level in subjects after completion of immunization with the polybacterial vaccine, whereas the response was small and transient following oral immunization with the monobacterial vaccine. Clonal analysis of the proliferative response demonstrated that the precursor frequency of HI antigen-specific cells in the circulating pool was not expanded to account for the differences, despite repeated ingestion of the vaccine. An analysis of PBL following oral immunization using anti-TAC monoclonal antibody revealed an increase in the number of IL-2 receptor-bearing cells in subjects orally immunized with the polybacterial vaccine, with maximal numbers occurring at day 62 when the number of precursors fell but the proliferative response remained high. This suggests that the enhanced and sustained proliferation in bulk cultures is due in part to a contribution to the overall proliferation by in vivo polyclonally-activated IL-2 receptor positive cells which proliferate in the presence of IL-2. Taken together, the results obtained are consistent with the concept that 'restricted' cell activation may be important in the mechanism of selective protection found following oral immunization with monobacterial HI vaccine.

Administration, Oral↗
PubMed1986

Intracellular pH regulation during prolonged hypoxia in rats.

Conscious rats maintained for three weeks at PB 370-380 Torr were studied in a chamber where PIO2 was maintained at 68-70 Torr at ambient barometric pressure (740-750 Torr). Controls were pair-fed rats maintained at ambient barometric pressure and studied at ambient PIO2 for 4 h. Steady-state intracellular pH (pHi) of left and right ventricle, and of tibialis anterior, quadriceps and diaphragm was determined from the distribution of 5,5-dimethyl-2,4-oxazolidinedione (DMO). Apparent non-bicarbonate buffer value (beta app) was calculated as the ratio of the change in HCO3- concentration to the change in pH elicited by the increase in PCO2. beta app of plasma, tibialis anterior, quadriceps and diaphragm was approximately 2, 3, 6 and 12 times higher, respectively, in hypoxic than in normoxic rats. Neither left nor right ventricular beta app was significantly changed by prolonged hypoxia. In the hypoxic animals, bilateral nephrectomy abolished the increase in beta app of plasma, tibialis anterior and quadriceps, and moderated the increase in beta app of diaphragm. No significant effect of nephrectomy was observed in beta app of either left or right ventricle. The results indicate that in the skeletal muscles studied under conditions of an acid load in the form of increased PCO2, intracellular pH is better regulated in hypoxic than in normoxic rats. The effects of nephrectomy suggest that this is due, at least in part, to a more effective renal compensation in hypoxic than in normoxic rats. Prolonged hypoxia, on the other hand, does not affect the cell pH regulation of right or left ventricle.

Acid-Base Equilibrium↗
PubMed1986

Renal compensation of hypercapnia in prolonged hypoxia.

We previously showed that rats made hypoxic for three weeks were able to regulate their plasma pH better than normoxic rats during acute hypercapnia. This improved pH regulation was abolished by nephrectomy, suggesting that it was due, at least in part, to a more effective renal compensation of hypercapnia in hypoxic rats. To test this possibility renal acid excretion was measured in conscious rats that had been kept at PB 370-380 Torr for three weeks. The rats were studied in a chamber where PIO2 was kept at 68-70 Torr at ambient PB (740-750 Torr). Controls were pair-fed normoxic rats. After a 2 h control period, inspired PCO2 was increased for 4 h. The apparent non-bicarbonate buffer value of arterial blood plasma was twice as high in the hypoxic than in the normoxic rats. Renal excretion of ammonium increased to a similar extent during hypercapnia in both normoxic and hypoxic rats. Titratable acid excretion of normoxic rats did not change significantly during hypercapnia. In the hypoxic rats, on the other hand, total excretion of titratable acid in the 2 h control period was 90.9 +/- 16.4 mumol/rat; and increased to 150.0 +/- 13.4 mumol/rat in the first 2 h and to 232.9 +/- 26.0 mumol/rat in the last 2 h of hypercapnia. In spite of this large increase in acid excretion, urine pH of hypoxic rats did not change significantly, indicating a higher buffer value of the urine of hypoxic rats. These results confirm our previous observations and support the idea that the improved pH regulation of hypoxic rats is due in part to a more effective renal compensation of hypercapnia.

Animals↗
PubMed1986

Acid-base regulation in prolonged hypoxia: effect of increased PCO2.

Conscious rats maintained for 3 wk at PB 370-380 Torr were studied in a chamber where PIO2 was kept at 68-70 Torr at ambient barometric pressure (740-750 Torr). Blood samples were obtained through an arterial catheter. Controls were pair-fed rats maintained at ambient barometric pressure and studied at PIO2 68-70 Torr for 4 h (acute hypoxia) or at ambient PIO2 (normoxia). Arterial blood pH of 3-wk hypoxic rats was not different from that of normoxic rats. Hypercapnia was produced by increasing PICO2 for 4 h. The 3-wk hypoxic rats showed the highest apparent non-bicarbonate buffer value of arterial blood (beta app): 77 mmol/(pH X kg), compared to 38 in normoxia and 43 mmol/(pH X kg) in acute hypoxia. Comparison of beta app at different times of hypercapnia in intact and in nephrectomized rats suggests that the high beta app of prolonged hypoxia is largely due to an increased renal compensation, and, to a smaller extent, to increased chemical buffering. While the extracellular fluid of normoxic and acute hypoxic rats showed a net gain of base of non-renal origin during hypercapnia, the 3-wk hypoxic rats showed a net non-renal base loss, which may be masked by the increased renal compensation.

Acid-Base Equilibrium↗
PubMed1986

Characterisation of the host response to Plasmodium falciparum infection in acute non-complicated malaria.

In this study we have examined serum from patients with Plasmodium falciparum malaria, collected at the time of acute attack and 14 days later. We have also examined sequential samples of sera taken from children living in Madang Province, Papua New Guinea, an area endemic for malaria. The total amount of antibody directed against P. falciparum in acute phase sera was less than that found in matched controls. An in vitro assay measuring inhibition of penetration of uninfected erythrocytes by merozoites of P. falciparum revealed less inhibitory activity in acute phase sera than in matched controls. The longitudinal study of sera from village children demonstrated that non-specific inhibition of intracellular parasite growth was fairly stable, while merozoite inhibiting activity was unstable and varied with time. A cloned P. falciparum species has been used to directly demonstrate the specific growth enhancement by serum in vitro.

Acute Disease↗
PubMed1986

Characterisation of the host response to Plasmodium falciparum infection. I. Cerebral malaria.

Cerebral malaria is a major form of complicated malaria consequent upon cerebral damage associated with endothelial cell necrosis. We have used assays of Plasmodium falciparum growth inhibition in vitro to study serum inhibitory factors in patients with cerebral malaria. Serum from children with cerebral malaria inhibited parasite growth in a non-synchronised 72-hour assay to a greater extent than did sera from immune adults or asymptomatic children (p less than 0.001). The high level of non-specific inhibition of parasite growth was particularly evident when sera were tested against three P. falciparum isolates, and contrasted with the inhibitory effect of sera from non-malaria febrile controls. In this study, serum from patients with cerebral malaria was more inhibitory than serum from the other groups (p less than 0.001) and its between-isolate variation, when tested against a panel of P. falciparum isolates in growth assays, was significantly less than that of the other groups tested (p less than 0.005). These results are consistent with the hypothesis of toxin-induced endothelial cell damage, with the sequence of pathogenic events involving host-derived serum factors capable of damaging P. falciparum.

Adolescent↗
PubMed1986

Regulation of IgA secretion in polyclonally induced in vitro human lymphocyte cultures: the function of T and B cells from mesenteric lymph nodes and peripheral blood.

Human gut-associated immunoregulatory events were studied in a pokeweed mitogen (PWM)-stimulated culture system using lymphocytes obtained from the mesenteric lymph nodes (MLN) of female subjects undergoing gastroplasty for obesity. Compared with peripheral blood lymphocytes, lymphocytes obtained from MLN secreted IgG, IgA and IgM isotypes that differ in pattern and distribution despite similar proportions of T cells and B cells expressing isotype-specific surface membrane immunoglobulin (SmIg). Among the isotypes secreted, IgA appeared to be increased relatively to other isotypes in MLN cultures. Crossover coculture experiments using T and B cells isolated from both MLN and blood by E-rosetting and cell panning procedures demonstrated that IgA was particularly sensitive to help and suppression exerted by MLN T cells and T cell subsets defined by monoclonal antibodies OKT4 and OKT8 respectively, when compared with similar subsets isolated from blood. The results presented provide a basis for study of gut handling of ingested antigen in man, and of disturbed immunoregulatory events in inflammatory and neoplastic disease of the human gut.

Adult↗
PubMed1986

Quantitation of isotype specific Haemophilus influenzae antibody in serum and saliva of normal subjects and chronic bronchitics.

An immunoglobulin isotype specific radioimmunoassay procedure has been developed to assess the antibody response to Haemophilus influenzae somatic antigens in serum and mucosal secretions. This assay was reproducible (between assay CV% 13.9; within assay CV% 4.5 IgG, 3.9 IgA, 3.0 IgM) and specific for H1/H2 antigens. Different patterns of antibody were observed in healthy children (aged 5-10 years), adults and patients with chronic bronchitis. In serum, 20% of chronic bronchitics had antibody levels greater than those observed in healthy adults. In saliva, the proportion of chronic bronchitic patients with high levels (greater than 12% binding) of IgG specific antibody was significantly greater (P less than 0.05) than in healthy adults or children. The proportion of children and chronic bronchitics which had antibody levels of up to 4% binding was significantly greater (P less than 0.05) than that observed in healthy adults. A similar pattern was observed for IgM specific antibody. The occurrence of IgA specific antibody in the saliva in children and chronic bronchitics was consistently greater than that observed in adults for all levels of antibody (P less than 0.05). Chronic bronchitics with high levels of antibody had greater infection and mortality rates.

Adolescent↗
PubMed1986

Breast feeding conditions a differential developmental pattern of mucosal immunity.

A prospective study of 146 children was conducted to evaluate the influence of infant feeding patterns on the development of mucosal immunity. First, there was a trend towards lower IgG concentrations in the breast-fed neonate, indicating a possible earlier 'closure' mechanism of membrane permeability. Second, the post-natal increase in IgA was earlier and greater in formula-fed infants. Third, IgM was detected earlier, more frequently, and at higher levels in formula-fed infants.

Aging↗
PubMed1985

Interleukin-2 production and bone-resorption activity in vitro by unstimulated lymphocytes extracted from chronically-inflamed human periodontal tissues.

Lymphocytes isolated from chronically-inflamed tissues were assessed for their ability to produce lymphokines without further stimulation in vitro. Cells were extracted from tissue obtained from 42 patients undergoing periodontal surgery. Cultures were set up in triplicate and supernatants collected after 48 h were assayed for interleukin-2 (IL-2) or bone-resorptive activity. IL-2 was assayed in the cultured supernatants from 20 patients using a previously-standardized T-cell growth assay, with maximally-stimulated peripheral blood-lymphocytes as a positive control. Bone-resorptive activity (BRA) was assessed in culture supernatants from another 22 patients using an in-vitro mouse-calvaria culture-system in which calcium release was measured with a calcium analyser. IL-2 was detected in 12 out of the 20 unstimulated cultures; BRA was detected in 14 of the 22 unstimulated cultures. There appeared to be no relationship between IL-2 production and BRA and the severity of the disease as assessed by loss of attachment. Nevertheless, it seems that most of the cells extracted from chronically-inflamed tissue were producing lymphokines which may indicate stimulation in vivo prior to cell extraction.

Adult↗
PubMed1985

The development and ultrastructure of Plasmodium falciparum damaged in vitro by human "crisis" sera and by chloroquine.

P. falciparum malaria was cultured in vitro in the presence of sera from patients with cerebral malaria, meningitis and also after chloroquine administration. Intra-erythrocytic parasite damage was seen by light and electron microscopy. The significance of the results is discussed with relevance to non-specific immune mechanisms, and the damage induced by these mechanisms compared with that from chloroquine.

Adolescent↗
PubMed1985

Analysis of patterns of growth inhibition of P. falciparum in synchronised cultures induced by serum from children and adults from Madang, Papua New Guinea.

In this study we have modified a micro Plasmodium falciparum in vitro growth inhibition assay to allow dissection of growth inhibition induced by test sera into two categories: inhibition of intracellular schizont growth and inhibition of uptake of merozoites into a second cohort of erythrocytes. This was achieved using morphology-controlled synchronised cultures with incubation times restricted to cover either ring to schizont development or schizont to ring development. Sera tested were obtained from a large prospective study of healthy residents of Madang, Papua New Guinea, who were carefully documented with respect to presence of malarial parasites in the blood, spleen size, age, sex and history of fever. In the ring to schizont assay sera from all the children tested inhibited parasitic growth by at least 20%, compared to only 10 of 39 adults tested (P less than 0.0005). In the schizont to ring assay 20 of 39 adult sera tested inhibited the uptake of 14C-isoleucine into P. falciparum protein compared to 3 of the 15 children's sera tested (P less than 0.01). These results are interpreted as reflecting a switch from non-specific mechanisms of resistance with increasing age.

Adolescent↗
PubMed1985

D-penicillamine induced suppression of B cell function: in vivo effect of D-penicillamine.

We assessed the immunoglobulin secretory capacity of circulating B lymphocytes in 9 patients with classical rheumatoid arthritis (RA) before and after treatment with D-penicillamine. Peripheral blood lymphocytes (PBL) from patients with RA spontaneously synthesized more IgG and IgA than normals. The secretory rate of rheumatoid PBL could not be induced by the polyclonal activator, pokeweed mitogen (PWM). The presence of D-penicillamine in cultures significantly suppressed PWM stimulated immunoglobulin synthesis of control PBL but did not inhibit synthesis of mitogen stimulated RA PBL. After D-penicillamine therapy for 3 months immunoglobulin synthesis by PBL from patients with RA was reduced with or without PWM. The T mu:T gamma ratio was also decreased after therapy. These results support the hypothesis that D-penicillamine selectively impairs helper T cells in vivo, preventing the T dependent expansion and activation of B cells characteristic of RA.

Adult↗
PubMed1985

The relationship between atopy and salivary IgA deficiency in infancy.

In a prospective study, infants born to atopic parents had a significantly higher prevalence of salivary IgA deficiency at all ages studied than control infants, and the mean non zero IgA level of the potentially atopic infants was significantly lower at 8 and 12 months than of control infants. Of the infants with atopic parents, the prevalence of IgA deficiency was not significantly greater in those who manifested atopic disease during the study period than in those who did not, but the levels were significantly lower at 4 months.

Aging↗
PubMed1984

Catecholamine effect on HCO3-/Cl- exchange and rabbit myocardial cell pH regulation.

The possible effect of isoproterenol on a HCO3-/Cl- exchange in mammalian myocardium and its role on intracellular pH (pHi) regulation was studied in isolated perfused rabbit hearts. pHi was determined from the distribution of 5.5-dimethyl-2,4-oxazolidinedione (DMO). Perfusates contained either 137.4 or 4.4 mM Cl-. In the latter case, Cl- was replaced by glucuronate. Hearts were perfused with low [Cl-] Ringer for 1 h in order to deplete the cell of Cl-. Isoproterenol (10(-5) M) was infused for the last 15 min of perfusion in approximately half of the preparations. Reduction of [Cl-], both in the untreated and in the isoproterenol-treated preparations resulted in an increase in pHi. Isoproterenol increased tissue cAMP concentration by approximately 2.5 fold both in hearts perfused with normal and with low [Cl-] Ringer. In the presence of normal [Cl-], isoproterenol had an alkalinizing effect when acid loads were introduced. This effect was abolished by the reduction of [Cl-]. These results support the idea that the catecholamine-cAMP system stimulates a HCO3-/Cl- exchange in mammalian myocardium.

Acid-Base Equilibrium↗
PubMed1984

Non-specific immunity to Plasmodium falciparum: in vitro studies.

Peripheral blood mononuclear cells (PBM) were cultured with Plasmodium falciparum malaria for several cycles of parasite growth. Non-immune PBM inhibited P. falciparum more frequently than immune PBM. The inhibiting factor appears to be released during the first 24 hours of culture and is a non-dialysable factor, probably originating from monocytes. The relevance of these findings to in vivo immunity is discussed.

Cell-Free System↗