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Biomedical subjects

J S McCarthy

Publications and source records attributed to J S McCarthy.

At least 19 recordsLinked to original sources
PubMed1997

Onchocera volvulus: characterization of a highly immunogenic Gln-rich protein.

A pool of sera from individuals classified as putatively immune (PI) to Onchocerca volvulus infection was employed in the screening of a fourth-stage larval cDNA expression library. A highly immunogenic clone, encoding the Ov 53/80 protein, was identified. The full length cDNA of clone 4.21 contained 2527 nucleotides encoding 769 amino acids of which 100 are glutamine residues (13%). Antibodies raised against recombinant protein encoded by a partial cDNA sequence (clone 73-k) recognized a 53 and 80 kDa protein in O. volvulus larval and adult parasite extracts, respectively. The antibodies localized the native protein in the cuticle, hypodermis, secretory vesicles and in granules of the glandular esophagus of larvae and in the hypodermis and the cuticle of adult worms. The recombinant 73-k polypeptide (r73) was recognized by 90-100% of sera from PI and infected individuals from Liberia, but only by 67% of similar groups from Ecuador. r73 specific IgG2 and IgG3 levels in the PI from Liberia and Ecuador, respectively, were significantly lower than in the infected, whereas the r73 specific IgG1/IgG3 or IgG1/IgG2 in the PI and the infected individuals from Liberia or Ecuador, respectively, were similar. The IgG4 specific antibody response in the PI from Liberia and Ecuador were lower than in the infected. The T-cell proliferative responses to r73 in infected individuals from Cameroon were found to be inversely correlated with their levels of microfilariae.

Amino Acid Sequence↗
PubMed1996

Evaluation of a polymerase chain reaction-based assay for diagnosis of Wuchereria bancrofti infection.

To assess the utility of a polymerase chain reaction (PCR)-based method for diagnosis of Wuchereria bancrofti infection, blood, plasma, and paraffin-embedded tissue samples were tested using a PCR-based assay that detects a W. bancrofti-specific repetitive DNA sequence. The assay was positive in 100 microL of blood from 40 of 42 microfilaria-positive subjects, the 2 subjects with negative assays having microfilarial counts of 1. Samples from 127 uninfected subjects were PCR-negative. The assay was also positive in 7 of 10 daytime samples in regions where infection is nocturnally periodic; PCR amplification from paraffin-embedded sections established the diagnosis of W. bancrofti infection in another 2 cases. A microtiter ELISA plate-based method was developed for rapid evaluation of large numbers of samples. These results suggest that this PCR-based assay will be useful in diagnosis of W. bancrofti infection in a variety of clinical settings.

Adult↗
PubMed1995

Clearance of circulating filarial antigen as a measure of the macrofilaricidal activity of diethylcarbamazine in Wuchereria bancrofti infection.

Small doses of diethylcarbamazine (DEC) clear microfilariae (MF) from the blood of Wuchereria bancrofti-infected persons, but the dose and regimen required to kill adult worms is not clearly defined. A prospective study was undertaken to examine the macrofilaricidal effect of DEC and the ability of an assay for circulating filarial antigen (CFA) to define the effect. Twenty-five MF-positive subjects and 7 MF-negative but CFA-positive subjects were treated with DEC and followed for 18 months. Of the 25 MF-positive patients, 24 cleared MF, and 22 of 26 CFA-positive subjects cleared CFA. A significantly greater decrease in antifilarial IgG4 was seen in patients who cleared CFA than in those who did not. The complete clearance of CFA observed after therapy with DEC indicates that assessment of CFA clearance is a useful means for detecting macrofilaricidal effects of antifilarial chemotherapy.

Adolescent↗
PubMed1994

Long-term effect of prenatal exposure to maternal microfilaraemia on immune responsiveness to filarial parasite antigens.

To identify long-term effects of prenatal exposure to maternal filarial-parasite infection, we assessed lymphocyte responses in 21 Polynesian children born 17-19 years previously to mothers diagnosed as being microfilaraemic or infection-free. All children lived on an island endemic for bancroftian filariasis but were free from infection at the time of study. While children (n = 10) of infection-free mothers responded vigorously to microfilarial antigen with lymphocyte proliferation, production of interleukin 2 (IL-2), IL-5, IL-10, granulocyte macrophage colony-stimulating factor (GM-CSF), and interferon gamma (IFN-gamma), cellular hyporesponsiveness was seen in children (n = 11) born to microfilaraemic mothers. The hyporesponsiveness appeared restricted to microfilarial antigens and did not extend to non-parasite antigens. These findings suggest that hyporesponsiveness resulted from in-utero acquisition of tolerance to microfilarial antigens in chronically-infected mothers.

Adolescent↗
PubMed1994

Onchocerciasis in endemic and nonendemic populations: differences in clinical presentation and immunologic findings.

To characterize the clinical and laboratory features of onchocerciasis in visitors to endemic areas and to compare them with those seen in endemic subjects, 20 returned visitors and 21 endemic subjects with onchocerciasis were evaluated. Dermatitis was the most frequent clinical finding among the returned visitors. None had nodules or eye disease and, in contrast to the endemic subjects, microfiladermia was often absent or of low density. All persons studied had antibody responses measurable by ELISA to both soluble Onchocerca volvulus antigen and a panel of diagnostic recombinant antigens. Eosinophil and IgE levels were significantly higher in the endemic group, as was the capacity of peripheral blood mononuclear cells from this group to produce the T helper cell-like cytokines interleukin-4 and -5. It is likely that the chronicity and intensity of infection in endemic subjects account for the clinical and immunologic differences observed between the 2 groups.

Cells, Cultured↗
PubMed1978

Age-dependent closure of the patent ductus arteriosus by indomethacin.

Indomethacin has been shown to be effective in closing a patient ductus arteriosus (PDA) in small premature infants. However, the age range over which this therapy is effective remains undetermined. Eighteen infants ranging in age from 4 to 45 days were studied. All had auscultatory and clinical findings indicative of PDA. Seventeen had roentgenographic evidence of cardiomegaly and/or increased pulmonary vascular markings, and eight had ECG evidence of ventricular hypertrophy. Indomethacin was administered to most patients in two doses of 0.1 to 0.3 mg/kg 24 hours apart. In eight of 12 patients, 3 week of age or younger, the PDA closed after indomethacin therapy. Two patients had a decrease in the intensity of murmur and improvement of congestive heart failure after treatment, but the PDA did not close completely. Only patients 33 weeks of age (actual age) or younger responded to indomethacin therapy with complete ductal closure. The condition of patients 34 to 36 weeks of age improved but there was not complete closure; in patients older than 36 weeks there was no response. The data suggest an age-related mechanism for PDA closure and that treatment with indomethacin before 33 weeks of age is probably required. A role for prostaglandin in ductal patency is postulated.

Age Factors↗
PubMed1972

The effect of sulfonylurea drugs on rabbit myocardial contractility, canine purkinje fiber automaticity, and adenyl cyclase activity from rabbit and human hearts.

Long-term clinical studies have associated tolbutamide therapy with an increased incidence of cardiovascular deaths. The effects of this and other sulfonylurea drugs on contractility and rate of isolated rabbit atria, automaticity of isolated dog Purkinje fibers, and adenyl cyclase activity in particulate preparations of rabbit and human hearts were studied. At concentrations that are attained clinically, tolbutamide (10 mg/100 ml) increased contractility of driven rabbit atria to 124+/-5% of control, acetohexamide (3.9 mg/100 ml) to 140+/-5%, chlorpropamide (8.3 mg/100 ml) to 139+/-6%, and tolazamide (3.1 mg/100 ml) to 119+/-6%. These effects were accentuated in the presence of 2.5 x 10(-4) M theophylline and were not blocked by 1 x 10(-5) M propranolol. Adenyl cyclase was activated by each of these drugs at concentrations below those which increase contractility. The drugs also increased the rate and slope of phase 4 depolarization in spontaneously beating Purkinje fibers, but did not alter the spontaneous rate of isolated rabbit atria. Since inotropic and chronotropic stimulation can be deleterious in some clinical settings, these findings may be of significance in interpretation of cardiovascular mortality data.

Acetohexamide↗