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Biomedical subjects

J Fletcher

Publications and source records attributed to J Fletcher.

At least 289 records · Page 16Linked to original sources

A quantitative study of the development of sudanophilic lesions in the aorta of rabbits fed a low-cholesterol diet for up to six months.

Eighteen New Zealand white rabbits were placed on a diet containing 0.25% cholesterol and 6% corn oil for periods of up to 6 months. The animals were divided into 4 gours and sacrificed after 2, 3, 4, and 6 months. The aortae were removed, stained with Sudan III, and analyzed with the polar coordinate technique. While the periorificial lesions developed more slowly on this diet than on the diet with 2% cholesterol and 6% corn oil we had used previously, there was no differences in either the location or the shape of the lesions. In the descending thoracic aorta, lesions developed initially distal to orifices; however, significant lateral and proximal components were observed as atherogenesis progressed. The coronary lesions completely surrounded the ostia in all stages of development. The total area of the lesions was more related to time (r = 0.74, P less than 0.01), than to serum cholesterol (r - 0.51, P less than 0.05) or to cholesterol-time product (r = 0.69, P less than 0.01).

Animals↗

Artefacts of localization of atherosclerosis in pinned aortas.

Detailed studies of aortas from 8 rabbits showed that serious artefacts occur if the aortas are pinned at their in vivo dimensions, rather than fixed at physiological pressure. In the pinned aortas, the proximal parts of the branches were pulled up onto the aortic wall. This was more pronounced for the large branches of the abdominal aorta than for the smaller intercostal branches. This artefact caused atherosclerotic lesions, which had developed at the origin of the branch, to appear as if they were entirely on the aortic wall. We found that a marked change in the elastin pattern was present at the origin of the branch; this can be used to mark the true origin of the branch. With the pressure technique we found that lesions had different shapes and locations at different branch points.

Animals↗

A 'new' blood group antigen Fra: incidence, inheritance and genetic linkage analysis.

Investigation of the inheritance of a 'new' low-incidence red cell antigen (Fra) indicates that it is an autosomal dominant marker and not part of the ABO, MNSs, P, Rh, Kell, Lutheran, Duffy, Kidd, Dombrock or Scianna blood group systems. No genetic linkage was established between 3Fr, the locus governing production of Fra, and any of 21 other markers.

Blood Group Antigens↗

Impaired neutrophil function and myeloperoxidase deficiency in myeloid metaplasia.

The ability of neutrophils to phagocytose and kill Candida guilliermondii was investigated in 12 patients with myeloid metaplasia (MM). Following ingestion there was a considerable impairment in the ability of MM neutrophils to kill and digest Candida which was not explained by the very mild impairment in phagocytosis. Quantitative myeloperoxidase measurement revealed an overall deficiency of this enzyme in MM neutrophils and a highly significant correlation between low myeloperoxidase levels and impaired candidacidal activity. Neutrophils from patients with myeloid metaplasia show a pattern of defective microbial killing, high alkaline phosphatase activity and low myeloperoxidase activty which is similar to that seen in severe infections and distinct from chronic granulocytic leukaemia. The cells of one patient with particularly low myeloperoxidase and defective microbial killing were further studied both cytochemically and by electron microscopy. The azurophilic granules of his neutrophils were present in normal numbers and contained normal amounts of acid phosphatase but they lacked myeloperoxidase.

Candida↗

Carcinoma of the lung presenting with a myeloproliferative disorder. A report of two patients.

A myeloproliferative disorder, similar to agonogenic myeloid metaplasia, has been described in patients with cancer. Two patients with carcinoma of the lung are described who presented with such a disorder but in whom there was no evidence of bone marrow fibrosis and in one of whom there was no evidence of bone marrow infiltration by tumor. The possible mechanism of this association is discussed.

Aged↗

Normal meiosis in two 47,XYY men.

Details of testicular histology and meiosis are given for two 47,XYY men, one an oligospermic childless individual, the other a fertile man with near-normal spermatogenic activity in his testes. Examination of the chromosomes at meiosis, with "Q" and "C" staining, gave no evidence for the occurrence of the second Y chromosome in the germ line of either individual.

Adult↗

Effect of malnutrition on susceptibility of mice to Trypanosoma musculi: vitamin A-deficiency.

Vitamin A-deficiency was studied in mice infected with Trypanosoma musculi. Irrespective of diet, trypomastigotes (trypanosomes) appeared in peripheral tail blood of all inoculated mice after 6-day incubation periods. On the average, vitamin A-deficient mice had parasitemias about 10 times greater than animals fed a complete diet and 8 times pair-fed controls. Parasitemias lasted longer in vitamin-deficient hosts, and reached a maximum five days later than those from control hosts.

Animals↗

The effect of the duration of cholesterol feeding on the development of sudanophilic lesions in the rabbit aorta.

Polar coordinate mapping was used to determine the rate of growth of individual sudanophilic lesions on the aortic wall around several major branches of the aortae of cholesterol fed rabbits. Four groups, with 6 8-month old male albino white rabbits in each, were used in the study. One group served as a control and the remaining 3 were fed a diet of 2% cholesterol and 6% heated corn oil mixed with ground rabbit pellets for 4, 8, and 10 weeks each. Animals were sacrificed, the aortae removed, stained with Sudan III, pinned at in vivo dimensions, and mapped by the polar coordinate method. No sudanophilic lesions were observed in the control animals. In the experimental groups, the early lesions, except the coronaries, were almost entirely distal to the orifices, and maintained roughly the same contour while spreading around the orifice. The coronary lesions completely encircled the orifices as described previously. As lesions progressed, they became elevated and often granular, so that the lesions themselves may have affected flow profiles around the orifices. Lesions around adjacent orifices were fused in 48% of the cases after 10 weeks on the diet, as opposed to 2% after 4 weeks on the diet. More prolonged experiments were not possible with this diet as the animals developed jaundice and diarrhea. Hemodynamically, these results suggest that early sudanophilic lesions in cholesterol-fed rabbits develop on the aortic wall in areas of high shear stress.

Animals↗

Defective neutrophil function in chronic granulocytic leukaemia.

The ability of neutrophils to phagocytose, kill and digest Candida guilliermondii was investigated in twelve patients with chronic granulocytic leukaemia (CGL). Following ingestion of organisms there was considerable reduction in the ability of CGL cells to kill Candida and this was not explained by a mild impairment of phagocytosis. Histochemical staining showed that granules containing lysosomal enzymes disappear form the cytoplasm of normal neutrophils during killing and digestion of the fungus, while in CGL cells the granules remain. Quantitative measurement confirmed loss of peroxidase from normal neutrophils during Candida killing but no loss from CGL neutrophils. The primary granules of CGL neutrophils do not fuse with and discharge their contents into the phagocytic vacuole and this explains their impaired ability to kill and digest Candida.

Candida↗

Cytogenetics and infertility in man. II. Testicular histology and meiosis.

Within a group of 207 subfertile men, selected for testicular biopsy, histological investigations were made successfully in 194 chromosomally normal and 7 chromosomally abnormal individuals. Fifty-two per cent of men with a normal karyotype showed normal testicular histology, 31% showed a general depression of spermatogenesis and 8% showed deficiency in the late stages. Ten per cent had only Sertoli cells in the testis. The range of testicular conditions seen in the chromosomally abnormal men was similar to that found in the chromosomally normal. Meiotic studies carried out on 118 chromosomally normal individuals gave a mean chiasma count of 48-9 per cell. There was a positive correlation between high numbers of cells at diakinesis/metaphase I showing X and Y univalents and low numbers of cells reaching metaphase II. Meiosis was studied in 3 translocation heterozygotes, one 47, XYY male, one 47, XY+mar individual and one patient with a ring Y chromosome.

Adult↗

A chromosome rearrangement in orangutan studied with Q-, C-, and G-banding techniques.

A constitutional chromosome rearrangement is a phenotypically normal male organutan is described. The rearrangement resulted from three breakages in chromosome 9 and involved a pericentric inversion and additional reciprocal transpositions of the terminal segments of both arms. Q-, G-, and C-banding studies were carried out, and it was shown that the chromosomes affected was a member of the only pair in the complement that lacked a centromeric C-band and that its G-banding pattern closely resembled that of chromosome 12 in man. The origin of the rearrangement and the role of such rearrangement in producing chromosome polymorphisms are discussed, particularly in relation to evolution and speciation. An additional pair of heteromorphic chromosomes (No.23) is also described. The short arm satellited region of one member of the pair was found to be variable and strongly C-banded.

Animals↗

Abortion, euthanasia, and care of defective newborns.

Growing use of abortion to prevent births of infants with unfavorable prenatal diagnoses raises ethical questions about active euthanasia for newborn infants with similar impairments. Two opposing ethical arguments are those of Paul Ramsey, who equates genetically indicated abortion with infanticide disapprovingly, and of Joseph Fletcher, who equates the morality of abortion with selective euthanasia approvingly. Though radically different, these arguments treat the ethical aspects of the prenatal and postnatal situations as essentially similar. There are, however, different moral features between the two situations, in that the postnatal situation is characterized by the independent physical existence of the infant, the possibility of treatment, and the formation of parental loyality to the infant. Thus, a decision for abortion after prenatal diagnosis does not necessarily commit parents to euthanasia in the management of a seriously damaged infant.

Abortion, Induced↗

Mouth lesions in iron-deficient anemia: relationship to Candida albicans in saliva and to impairment of lymphocyte transformation.

The atrophic glossitis and angular chilosis in patients with iron-deficient anemia are associated with infection of the mouth by Candida albicans. Saliva from these patients contained more Candida and supported the growth of Candida better than did saliva from a control group. The possibility that growth of Candida may be due to impaired lymphocyte function was investigated by measuring transformation of lymphocytes stimulated with phytohemagglutinin. Transformation was depressed in iron-deficient subjects and returned to normal after correction of their iron status. The lymphocyte count in the peripheral blood was also depressed and corrected by additional iron. Impaired lymphocyte function did not explain the mouth lesions and growth of Candida in saliva since lymphocyte transformation was equally depressed in patients with and without mouth lesions. A local factor, such as an effect of lack of iron on the resident vacterial flora of the mouth, may be important.

Adolescent↗