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Biomedical subjects

R M Dougherty

Publications and source records attributed to R M Dougherty.

At least 19 recordsLinked to original sources

Concentration of dietary N-6 polyunsaturated fatty acids and the human immune status.

We examined the effect of the dietary concentration of total fat and n-6 polyunsaturated fatty acids (PUFA) on the immune status of seven healthy women (age 30-65 years) who lived at our metabolic suite. During the first 20 days all subjects consumed a stabilization diet that contained 5.2 energy percent (en%) PUFA and 41.1 en% fat. For the next 40 days, three subjects consumed a diet with 3.2 en% PUFA and 26.1 en% fat, while the remaining four subjects consumed a diet with 9.1 en% PUFA and 31.1 en% fat. For the next 40 days, the diets of the two groups were crossed over. Blastogenesis of peripheral blood mononuclear cells cultured with phytohemagglutinin, concanavalin A, protein A, and pokeweed, and the serum concentrations of complement fractions C3 and C4 were significantly increased upon the feeding of both low fat (26.1 or 31.1 en%) diets compared to the values when the high fat (41.1 en%) diet was fed. None of the indices tested were different when the high PUFA (9.1 en%) and low PUFA (3.1 en%) diets were compared. Our results indicate that low fat diets improve some of the indices of human immune status and that a moderate increase in the level of n-6 PUFA in an otherwise low fat diet does not suppress the human immune system.

Adult

Lack of effect of linoleic acid on the high-density-lipoprotein-cholesterol fraction of plasma lipoproteins.

Low-fat, natural diets were fed to 11 middle-aged, healthy male subjects for two 40-d periods to determine effects on plasma lipoproteins. The diets were designed to maintain saturated and monounsaturated fatty acids at 10 en% and linoleic acid (LA) at 3.8 and 10.8 en%. When compared with baseline concentrations, total cholesterol decreased 10% at the end of the lower LA diet and 15% at the end of the higher LA diet. Low-density-lipoprotein cholesterol (LDL-C) decreased 18% and 22%, respectively, during the same periods. Plasma high-density-lipoprotein cholesterol (HDL-C) at the end of each dietary period was not significantly different but the midpoint values were lower by 12.5% on the lower LA diet and 7.3% on the higher LA diet. Apolipoprotein B decreased 27% at the end of the lower LA diet and 37% at the end of the higher LA diet whereas apolipoprotein A-I increased 18% and 24%, respectively. HDL-C was not reduced by dietary LA over a 6-wk period.

Apolipoprotein A-I

Platelet aggregation in humans is affected by replacement of dietary linoleic acid with oleic acid.

The effect of concentrations of linoleic acid (LA) on platelet aggregation was measured in seven healthy adult males. Subjects were randomly divided into two groups; these groups were fed natural food diets of identical composition except that one was high in LA (11.5% of energy) and low in oleic acid (OA) (7.4% of energy), the other was low in LA (4.5% of energy) and high in OA (15.7% of energy). The thresholds of ADP- and collagen-induced platelet aggregation were increased significantly by the high LA diet even though the intake of total fat and saturated fatty acids did not differ in these diets.

Adenosine Diphosphate

Dietary fat and blood pressure in humans.

The regulation of blood pressure by dietary means represents an important approach toward the reduction of morbidity and mortality of heart disease. The results of our dietary intervention studies demonstrated that a lowered saturated fat, higher polyunsaturated fat diet had a lowering effect on both systolic and diastolic blood pressure, and a lowering effect on blood lipids. These beneficial effects were accomplished without drastic changes in the typical Western diet. The amount of meat, dairy products, fish and eggs was not altered from the usual intake, while the intake of fruits, vegetables and grains increased. As a consequence of altering the diet, we have found that the blood pressure lowering effect appears to be mediated through linoleic acid (n-6). It is evident from these results that the role of diet must be given serious consideration for the control of blood pressure.

Adult

Dietary polyunsaturated fat and hypertension.

A significant reduction in blood pressure has been observed during low-fat high poly unsaturated fattyacids/saturated fattyacid--ratio diets in a series of studies conducted in the U.S. and Finland. The results suggest the active role of linoleic acid but the effects of decreased intake of saturated fats and the concomitant changes in the intake of other dietary components cannot be ruled out.

Blood Pressure

Nutrient content of the diet when the fat is reduced.

When the fat content of the typical US diet was reduced from 40 to 44% of total energy (en %) to approximately 25 en % there was a marked improvement in the overall nutrient content of the diet. Cholesterol, saturated fatty acid, and monounsaturated fatty acid intake were decreased and the polyunsaturated fatty acid content was moderately increased. This kind of dietary change was achieved without changing the usual intake of meats, dairy products, fish, and eggs. As the amount of fat was decreased, carbohydrates in the form of grains, fruits, and vegetables were increased, providing an improvement in the vitamin and mineral content of the diet. Vitamin C, thiamin, riboflavin, niacin, B-6, B-12, and folates increased in the 25 en % diet. Potassium, calcium, magnesium, phosphorus, iron, zinc, and copper intake also increased when the dietary fat decreased.

Dietary Carbohydrates

Effects of dietary calcium on blood and tissue lipids, tissue phospholipids, calcium and magnesium levels in rabbits fed diets containing beef tallow.

Levels of lipids, calcium and magnesium in blood and tissue were examined in rabbits to determine the effects of 20% beef tallow diets containing three levels of calcium, less than 0.02, 0.8 or 1.6%. In plasma, the calcium-deficient (less than 0.02%) diet contributed to elevated cholesterol and phospholipid, but had no effect on triglyceride levels. Plasma calcium decreased in the calcium-deficient group and plasma magnesium decreased in the high-calcium (1.6%) group of rabbits. Lipid levels of some tissues varied with the level of dietary calcium. Cholesterol, total phospholipid, sphingomyelin and phosphatidylethanolamine were generally elevated in livers of calcium-deficient rabbits, but the individual phospholipids were decreased in skeletal muscle. Lungs of the calcium-deficient group also had lower phospholipid levels than the high-calcium group. Liver, kidneys, brain and adipose tissue triglyceride levels were highest in the high-calcium group. The calcium level of skeletal muscle was lower in the calcium-deficient group than in the high-calcium group. Calcium in brain and adipose tissue were highest in the calcium-deficient group. Except for adipose tissue, magnesium levels of the tissues studied were not affected by dietary calcium.

Animals

Pilot epidemiological studies in thrombosis.

Some differences in the blood of farmers in Nurmijarvi, Finland, Canino, Italy, and Beltsville, Maryland in the United States apparently were associated with differences, among the areas, in the farmers' diets. Those associations suggested that diets that are high in saturated fats (Nurmijarvi) could predispose humans to develop intravascular disease. Such predisposition has been observed in experimental animals. Low levels of the parameters that are considered active in such predisposition apparently were associated with diets that were low in saturated fats (Canino) or with diets that were low in saturated and high in unsaturated fats (Beltsville). Within the limits of the experimental design, the data from the three population groups indicated that a more comprehensive study might establish a relation between diet and intravascular disease in humans.

Adult

Contact transmission of avian leukosis virus.

Intravenous inoculation of four age groups of White Leghorn chicks with ALV-F42, a group A field strain of avian leukosis virus (ALV), indicated that persistent tolerant infection could be induced as late as 2 weeks post hatch, though most birds responded with neutralizing antibody. Contact infection by environmental exposure to ALV was 100% effective in newly hatched and 28-day-old chicks. All contact-infected birds responded immunologically after transient viremia. A follow-up of immune birds from these six groups demonstrated that active multiplication of ALV continued despite neutralizing antibody. Infectious virus was shed by oral and cloacal routes, as well as through vertical transmission by hens to their embryos. Up to 10(8) infectious units of virus/g of feces was shed by 12-day-old viremic birds, and to a lesser extent virus was also shed in saliva as measured by oral washing. The cycle of contact transmission was also evaluated by the assessment of the efficacy of four portals of entry, where exposed skin was most effective in permitting infection, followed by oral, nasal, and conjunctival routes.

Administration, Intranasal

Characterization of human papovavirus RFV: comparison with SV40 and BKV.

Human papovavirus, RFV, isolated from urine of a renal transplant patient was compared with two strains of SV40 and with the prototype human papovavirus, BKV. Neutralization tests showed that RFV and BKV are indistinguishable, while large-plaque (LP) and small-plaque(SP) isolates of SV40 gave a low but significant level of cross-reaction with rabbit or human antisera against RFV. DNA reassociation saturation tests using 125I-labelled RFV DNA show that BKV has 88% homology, and SP-SV40 has 29% homology to RFV. We conclude that RFV and BKV are nearly, if not totally, identical and are not SV40 variants.

Antigens, Viral

Pheasant virus: new class of ribodeoxyvirus.

Cocultivation of cells derived from embryos of golden pheasants or Amherst pheasants with chicken embryo cells infected with Bryan strain of Rous sarcoma virus resulted in the detection of viruses which appear to be endogenous in these pheasant cells. The pheasant viruses (PV) were similar to avian leukosis-sarcoma viruses (ALSV) in their gross morphology, in the size of their RNA, in the presence of a virion-associated RNA-dependent DNA polymerase (DNA nucleotidyltransferase; deoxynucleoside triphosphate: DNA deoxynucleotidyltransferase; EC 2.7.7.7), and in their growth characteristics. PV also serves as a helper for the glycoprotein-defective Rous sarcoma virus. However, PV was shown to be different from both ALSV and reticuloendotheliosis virus in the following properties: (i) PV does not have ALSV group specific antigens; (ii) the protein composition of PV is different from those of the other two groups of viruses; (iii) PV fails to complement the defective polymerase of alpha type Rous sarcoma virus; and (iv) PV RNA shows no detectable homology with nucleic acids of the other two groups of viruses. Thus, PV appears to be a new class of RNA viruses which contain RNA-dependent DNA polymerase.

Alpharetrovirus

Induction of tumors in Syrian hamsters by a human renal papovavirus, RF strain.

Injection of RF virus (RFV), a papovavirus isolated from human urine, into newborn Syrian hamsters induced subcutaneous sarcomas in 50% of the recipients with 18- to 48-week latent periods. Transplantation of 2 X 10(6) primary RFV-induced tumor cells into weaning hamsters caused tumors in 100% of the recipients within 1-2 weeks. Continuous tissue culture cell lines were established from two primary tumors; one of these was transplantable. An in vitro-transformed continuous cell line (RF-194) obtained by infection of primary hamster embryo fibroblasts with RFV was transplantable in weaning hamsters. Neither infectious RFV nor virion antigens were detected in transformed cells. No RFV was recovered when transformed cells were fused with permissive, human embryo kidney cells by means of inactivated Sendai virus. Immunoperoxidase staining was used to show that all three RFV-transformed cell lines contained an intranuclear T-antigen closely similar to that of simian virus 40(SV40)-infected cells. Most hamsters (84%) with primary or transplanted RFV tumors responded with antibodies that reacted with RFV T-antigen and the T-antigen of SV40-infected cells. Likewise, hamster antisera against SV40 T-antigen cross-reacted with RFV T-antigen. Adsorption of RFV T-antisera with an excess of lyophilized SV40-transformed cells removed all detectable activity against SV40 T-antigen but left significant activity against RFV T-antigen. The reciprocal adsorption produced an antiserum spedicic for SV40 T-antigen. Thus human and simian papovavirus T-antigens were related but immunologically separable.

Animals

A comparison of human papovavirus T antigens.

A comparison was made of the T antigens induced in transformed cells or infected permissive cells by representatives of three categories of human papovavirus. The transformed hamster cell lines employed contained T antigen induced by either the BK or RF strains of papovavirus associated with human renal allografts; the JC strain of papovavirus from progressive multifocal leukoencephalopathy (PML), or a variant of SV40 virus isolated from PML. The human papovavirus T antigens were also compared with that of a human cell line transformed by SV40 of simian origin. Anti-T antibody prepared in hamsters against each of the hamster cell lines was absorbed with crude T antigen from each cell line, and the unabsorbed and absorbed antisera were tested for residual T antibody against each cell line, or against infected permissive cells by immunoperoxidase (IP) staining and complement-fixation (CF) tests. In unabsorbed antisera, T antibodies from each cell line cross-reacted with all T antigens in IP tests, and CF tests showed that T antisera reacted preferentially with T antigen induced by homologous virus. Absorpminants. T antigens of the two urine-derived strains, BK and RF, were identical or nearly so, but were clearly separable from T antigens of JC virus, PML-derived SV40 or simian-derived SV40. JC T antigen was intermediate, being more closely related to T antigens both of BK virus and SV40 virus than the latter were to each other. The T antigen of PML-derived SV40 could be distinguished from the T antigen of simian-derived SV40 and the T antigen of the SV40 variant from human brain was more closely related to those of the other human-derived papovaviruses than was the T antigen of SV40 from monkey kidney.

Animals

Use of the unlabeled antibody immunohistochemical technique for the detection of human antibody.

Two methods have been developed which permit use of the unlabeled antibody immunohistochemical technique for detection of human antibody, without the need for immunization of humans with peroxidase. Human antibody to herpes simplex virus (HSV) reacted with human cell cultures infected with HSV was the experimental system. In the first method an attempt was made to employ rabbit peroxidase-antiperoxidase (PAP) soluble complexes in connectin with human antibody. This was done by sequential addition to the HSV-infected cells of (a) human anti-HSV, (b) rabbit antihuman globulin, (c) guinea pig antirabbit globulin (the bridging reagent) and (d) rabbit PAP. Strong specific staining of HSV-infected cells was obtained; however, difficulties were encountered with nonspecific reactions on uninfected cells. In the second method PAP soluble complexes prepared with baboon antiperoxidase were bridged to the human anti-HSV antibody by rabbit antihuman globulin. Because of the phylogenetic relatedness of human and baboon globulins this resulted in firm binding which gave strong specific staining of HSV-infected cells without significant reaction in uninfected cells.

Animals