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J MacFarlane

Publications and source records attributed to J MacFarlane.

11 recordsLinked to original sources

Mapping of a visceral leishmaniasis-specific immunodominant B-cell epitope of Leishmania donovani Hsp70.

We have shown that a member of the 70-kDa heat shock protein (Hsp70) family is a major target of the humoral immune response during Leishmania donovani infection. A recombinant fusion protein was recognized by sera from 92% (35 of 38) of patients with visceral leishmaniasis, including representatives from each of the major regions where it is endemic. Serological analysis of recombinant Hsp70, expressed by a series of deletion constructs, identified the carboxy-terminal region as the immunodominant site. This region, which is the most evolutionarily divergent part of the molecule, was recognized by all sera from patients with visceral leishmaniasis which exhibited an anti-Hsp70 response. Purified recombinant L. donovani Hsp70 was not recognized by sera from patients with cutaneous leishmaniasis, Chagas' disease, leprosy, malaria, or schistosomiasis. To determine the regions involved in antibody recognition, a series of overlapping peptides were synthesized on polyethylene pins by the Pepscan method, and a hexamer, EADDRA, was identified by the visceral leishmaniasis serum samples as an immunodominant B-cell epitope.

Amino Acid Sequence

Identification and characterisation of a Leishmania donovani antigen belonging to the 70-kDa heat-shock protein family.

A Leishmania donovani promastigote cDNA library was screened with serum obtained from a patient infected with visceral leishmaniasis. Sequence analysis of a clone obtained from this library revealed that the 600-bp insert corresponded to the carboxy-terminal region of an antigen related to the 70-kDa heat-shock protein family. The full-length sequence of the corresponding gene (1959 nucleotides) was determined after isolation of genomic clones. Genes encoding the antigen are present on a single chromosome as a series of approximately twelve 3.7-kb direct tandem repeats. The antigen can be identified as a 70-kDa heat-shock cognate protein by virtue of its molecular mass, sequence and constitutive expression during heat shock. It is expressed at all stages of the parasite life-cycle. Antibodies against the lambda gt11 fusion protein were detected in more than 50% of serum samples obtained from patients with visceral leishmaniasis, but were not detected in sera from patients with cutaneous leishmaniasis or Chagas' disease.

Amino Acid Sequence

Protective effect of dietary fibre against chemically induced bowel tumours in rats.

101 rats were fed one of four diets containing graded amounts of dietary fibre. Subcutaeous dimethylhydrazine (D.M.H.) was given to half the rats in each of the diet groups. Stool mass was found to be directly related to the amount of dietary fibre consumed, and the incidence of D.M.H.-induced colon carcinoma was reduced as dietary fibre increased.

Animal Feed

Antihypertensive therapy in patients above age 60. Third interim report of the European Working Party on High blood pressure in Elderly (EWPHE).

Three hundred forty nine hypertensive patients above the age of 60 have entered the double-blind multicentre trial of the European Working Party on High blood pressure in the Elderly (EWPHE). After stratification and randomisation half were treated with one or two capsules containing 25 mg hydrochlorothiazide and 50 mg triamterene and if blood pressure control was insufficient methyldopa was added up to 2 g daily; the other half received matching placebo. No significant differences between the groups were present prior to randomisation. A significant blood pressure difference of 25/10 mm Hg was obtained between the groups and maintained during two years of follow-up. No major disturbances in serum potassium or serum sodium were noted with the present drug combination. However, during the initial phase an increase in serum creatinine and serum uric acid was noted in the actively treated group, which was maintained for two years. Also glucose tolerance was impaired after 2 years in the actively treated group. A favourable influence on prognosis by active treatment can be expected on the basis of the blood pressure reduction and in the absence of major electrolytes disturbances. But this benefit must be proven by observed statistical differences in terminating events between the groups. Therefore the patients are being followed for a longer period of time and more patients are admitted into the trial.

Aged

Osteoclastomalike anaplastic carcinoma of the thyroid. Diagnosis by fine needle aspiration cytology.

Fine needle aspiration (FNA) of a neck mass yielded cytologic specimens containing two cell populations: multinucleated giant cells and smaller, round-to-oval, undifferentiated malignant cells. The giant cells were frequently so numerous as to obscure the other cells. The FNA cytodiagnosis of a rare anaplastic thyroid carcinoma containing osteoclastic giant cells was substantiated by the subsequent exploratory surgery and biopsy specimen. Immunohistochemical staining suggested a dual origin of the two cell populations.

Aged