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Biomedical subjects

J R Allen

Publications and source records attributed to J R Allen.

At least 199 records · Page 11Linked to original sources
PubMed1979

The effects of salt concentration and H-1 depletion on the digestion of calf thymus chromatin by micrococcal nuclease.

We have removed histone H1 specifically from calf thymus nuclei by low pH treatment, and studied the digestion of such nuclei in comparison with undepleted nuclei. By a number of criteria the nuclei do not appear damaged. The DNA repeat-length in nuclear chromatin is found to be the same (192 +/- 4 bp) in the presence or absence of H1. These experiments demonstrate that the core histone complex of H2A, H2B, H3, and H4 can itself protect DNA sequences as long as 168 bp from nuclease. Our interpretation is that this represents an important structural element in chromatin, carrying two full turns of superhelical DNA. Depending on conditions of digestion this 168 bp fragment may be metastable and is normally rapidly converted by exonucleolytic trimming to the well-known "core-particle" containing 145 bp. Larger stable DNA fragments observed indigestion of H-1 depleted nuclei appear to arise from oligomers assembled from 168 bp cores in close contact exhibiting trimming of 0-20 bp at the ends. Electrophorograms of undepleted nuclear digests reveal oligomer bands in several size classes, each corresponding to one or more combinations of 168 bp particles, H1-protected spacers of about 20 bp length, and particles with ends trimmed to varying degrees.

Animals↗
PubMed1979

Pathophysiology of dehydromonocrotaline-induced pulmonary fibrosis in the beagle.

The purpose of this study was to characterize the sequential hemodynamic alterations and pulmonary vascular lesions produced by a single pulmonary artery injection of the vasotoxic pyrrolic alkaloid dehydromonocrotaline in the young beagle. Normotensive pulmonary pressure was replaced by hypertension 21 days after injection. By 28 days, the pulmonary pressure and total pulmonary vascualr resistance of the experimental animals were significantly greater than the controls (p less than 0.01). Right ventricular work increased from a baseline mean of 0.58 to 1.40 kg . m/min. Morphological and morphometrical analyses revealed alveolar edema, increased numbers of alveolar macrophages, cellular hyperplasia in the alveolar septa, and a progressive interstitial fibrosis. The precise mechansims by which dehydromonocrotaline injection initiates and promotes pulmonary hypertension and pulmonary fibrosis still needs clarification; however, our data indicate that the fraction of air space is reduced relative to the fraction of tissue space, and this change occurs with concurrent fibrosis in the alveolar septa and an increased pulmonary arterial pressure although hypoxia was not clinically detectable.

Animals↗
PubMed1979

Absence of fatty livers in rhesus monkeys fed orotic acid.

Pairs of rhesus monkeys were fed for 10 wk a basal diet containing 1% orotic acid or 10% nonfat milk powders. Amounts of total lipids in the liver and hepatic morphology were normal after 10 wk indicating that orotic acid in the diet did not induce fatty livers in rhesus monkeys.

Animals↗
PubMed1979

Fatal nosocomial Legionnaires' disease: clinical and epidemiologic characteristics.

The occurrence, clinical, and epidemiologic characteristics of fatal nosocomial Legionnaires' disease were ascertained by examining a sample of autopsy specimens submitted by hospitals participating in the National Nosocomial Infections Study. Sections of lung tissue from 263 patients were submitted by 40 hospitals in 24 states. Legionnaires' disease was identified in 10 patients (3.8%) from six hospitals in five states. The clinical and epidemiologic characteristics of sporadic fatal nosocomial Legionnaires' disease were similar to those from cases that occurred during epidemics of Legionnaires' diseases. A case-control study showed that cases of Legionnaires' disease were associated with an increased occurrence of Legionnaires' disease during the period June through November, temperatures greater than 39.2 degrees C, and administration of corticosteroids before onset of pneumonia. Legionnaires' disease can occur as a fatal nosocomial pneumonia and has clinical and epidemiologic features that may be helpful in differentiating it from nosocomial pneumonia of other causes.

Adolescent↗
PubMed1979

DNA single strand breaks caused by 2,2',5,5'-tetrachlorobiphenyl and its metabolites.

Polychlorinated biphenyls (PCBs) are widespread environmental pollutants which have been shown to be carcinogenic. One possible mechanism for the apparent carcinogenicity of PCBs is their metabolism to phenolic metabolites through an arene oxide intermediate, with the arene oxide that is formed being the ultimate mutagenic or carcinogenic species. The ability of a tetrachlorobiphenyl and its phenolic and arene oxide metabolites to cause single strand breaks in DNA was therefore examined. 2,2',5,5'-TCB-3,4-epoxide was more potent in causing DNA single strand breaks than either 2,2',5,5'-TCB or a mixture of 3-hydroxy and 4-hydroxy-2,2',5,5'-TCB. These results support the idea that PCB epoxide may be involved in PCB carcinogenesis.

DNA, Single-Stranded↗
PubMed1979

Langerhans cells trap tick salivary gland antigens in tick-resistant guinea pigs.

In the infested skin of tick-resistant guinea pigs, indirect immunofluorescence techniques have revealed that antigens from the ticks' salivary glands are associated with discrete dendritic cells in the epidermis. Evidence is presented to support the suggestion that these antigen-retaining cells are Langerhans cells.

Adenosine Triphosphatases↗
PubMed1979

The in vitro binding of 2,2', 5,5'-tetrachlorobiphenyl metabolites to rat liver microsomal proteins.

The in vitro association of tritium labeled 2,2', 5,5'-tetrachlorobiphenyl (TCB) with the microsomal fraction isolated from rat livers has been investigated in a metabolizing system. It was found that the control microsomes, capable of only minimal TCB metabolism, had 92% of the total microsomal radioactivity associated with lipids, while only 61% was associated with the phenobarbital induced microsomal lipid. The radioactivity per mg microsomal protein was the same for both induced and noninduced microsomes; however, very important qualitative differences were found. Only the proteins of the induced system contained a protein (s) (MW = 45,000 g/mole) capable of specifically binding a TCB metabolite. This binding required metabolism and was TCB concentration dependent. The specificity of this association was confirmed by dialysis and this data could be analyzed by the Scatchard-Klotz equation. These calculations allowed the evaluation of the number of binding sites (38 micron moles/g of total microsomal protein) and the apparent binding constant (1.4 x 10(7) l/mole). These data are consistent with strong noncovalent interaction of a 2,2', 5,5'-TCB metabolites, but do not exclude the possibility of covalent binding of other non-dialyzable metabolites.

Animals↗
PubMed1979

The location of tick salivary antigens, complement and immunoglobulin in the skin of guinea-pigs infested with Dermacentor andersoni larvae.

Using indirect immunoflorescence techniques, tick salivary gland antigens (SGA) were demonstrable in cement deposited on the skin by ticks and in all layers of the epidermis of infested guinea-pigs close to the sites where ticks attached. The antigen remained in these sites for several days after ticks had detached. In tick-resistant but not in normal guinea-pigs, SGA, complement and IgG were deposited at the dermo-epidermal junction even at some distance from the attachment site. Complement was also demonstrable in epidermal vesicles which developed beneath larvae attached to resistant guinea-pigs. It is suggested that antigen-antibody reaction and complement activation at these sites may play a role in the development of skin lesions and the attraction of basophils to these areas in challenged tick-resistant guinea-pigs. Tick antigens were also found to be associated with dendritic suprabasal cells in the epidermis of resistant guinea-pigs. It has previously been proposed that such SGA-trapping cells are Langerhans cells. These cells, in the presence of specific antibody and complement, could also initiate epidermal lesions in resistant guinea-pigs.

Animals↗
PubMed1979

The basophil response in blood and bone marrow of tick-infested guinea pigs.

The concentrations of basophils in blood and bone marrow were monitored in guinea pigs subjected to primary and secondary infestations with larvae of Dermacentor andersoni. In these guinea pigs a significant increase of basophils was evident in peripheral blood. The response following the secondary infestation was more rapid and more intense than that following the primary infestation. Similar changes were also shown to occur in bone marrow. The possible significance of these responses in relation to acquired tick resistance in guinea pigs is discussed.

Animals↗
PubMed1978

Identification of Trypanosoma theileri as a contaminant in primary cultures of bovine retina.

T. theileri has been isolated from primary cultures of bovine retina and subcultered successfully for 2 passages in sub-confluent cultures. When cultures reached confluency no trypomastigotes or epimastigotes could be detected and attempts to recover trypanosomes from these cultures were unsuccessful. The presence of intracellular forms could not formally be excluded.

Animals↗
PubMed1978

Metabolism of lead-210 in juvenile and adult rhesus monkeys (Macaca mulatta).

Experiments were conducted measuring the gastrointestinal absorption and elimination of a single dose of lead-210 acetate in infant and adult rhesus monkeys. Urinary and fecal excretion of absorbed lead was followed for 23 days. Infant monkeys eliminated less and absorbed more orally administered lead. Adult animals excreted more absorbed lead in feces, while urinary excretion between adults and infants was similar. Increased absorption of administered lead and reduced fecal excretion of absorbed lead resulted in significantly greater body burden of lead-210 in infant animals. Blood lead values were increased in the infant animals, and were inversely correlated with body burden and percent absorption of ingested lead.

Aging↗
PubMed1978

Correlation of PCB body burden with behavioral toxicology in monkeys.

Eight monkeys fed 2.5 ppm PCB in their daily diet conceived, delivered and nursed five infants, three of which survived past weaning at four months of age. PCB residues in fat in the surviving infants at 8, 10 1/2, and 23 months of age declined linearly when plotted as log concentration versus time (first order clearance), and these functions extrapolated to presumed peak PCB levels of 21, 114, and 123 microgram/g fat (ppm) at 4 months of age. Behavioral tests on these three infants and four normal controls revealed hyperlocomotor activity at 6 and 12 months of age correlated with peak PCB body burdens. Higher peak PCB body burdens also were correlated with increased errors in five of nine learning tasks conducted between 8 and 24 months of age. Point estimates of zero-effect levels of PCB body burdens ranged around 21 ppm, although it was clear that even the monkey carrying only 21 ppm PCBs at four months of age exhibited some behavioral deficits persisting through the final testing at 24 months of age.

Animals↗
PubMed1978

Dehydroretronecine-induced skin tumors in mice.

Female Swiss mice susceptible to skin tumors received 6 sc injections and/or topical applications of dehydroretronecine, a metabolite of the pyrrolizidine alkaloid monocrotaline, and were observed for 15 months for tumor development. Of 92 animals examined, 63 had tumors at the site of application or injection; 47 of these had skin tumors, mainly basal cell and squamous cell carcinomas. These data indicate that dehydroretronecine is a proximate carcinogen capable of causing a high incidence of skin tumours in mice at the site of sc injection or topical application.

Administration, Topical↗
PubMed1978

Responses of nonhuman primates to a polybrominated biphenyl mixture.

In a series of experiments, rhesus monkeys have been given in their diets 0.3, 1.5, and 25 ppm of a commercial polybrominated biphenyl (PBB) (as FireMaster FF-1). The seven adult female monkeys receiving 0.3 ppm PBB have been on the treatment regime for 15 months and have consumed over 22 mg of PBB. During the initial 6 months of exposure, they lost weight and 2 of the animals develop sterile abscesses. At 6 months, 4 of the 7 animals had flattened and lengthened serum progesterone peaks. This change was correlated with an increase in length of their menstrual cycles. After 6 months of PBB exposure, the animals were bred. Two of the 7 animals showed excessive and prolonged implantation bleeding. Two abortions and 5 live births were recorded. All of the experimental infants were smaller than the controls at birth. The animals receiving a diet containing 1.5 ppm PBB for 36 weeks (total intake 70 mg) have shown a moderate weight loss and decrease in serum cholesterol. Similar changes have also been recorded in the group given the 25 ppm PBB diet for 14 weeks (approximately 500 mg total intake). In addition, these animals have also developed a hyperplastic gastritis.

Animals↗
PubMed1978

Toxicity of firemaster FF-1 and 2,2',4,4',5,5'-hexabromobiphenyl in cultures of C3H/10T 1/2 mammalian fibroblasts.

A procedure for purifying 2,2', 4,4',5,5'-hexabromobiphenyl (HBB) from FireMaster FF-1 in gram amounts by crystallization is presented. Following purification, the structural assignment of HBB was made by using proton and carbon-13 nuclear magnetic resonance (NMR) spectroscopy, elemental analysis, and mass spectroscopy (MS). The growth of C3H/10T 1/2 cells treated with 5, 37, 75, and 150 microgram of HBB and FF-1 per milliliter of medium was measured at 4, 8, and 13 days following treatment. FF-1 was more toxic at 37 and 75 microgram/ml at both 4 and 8 days, but the same at 13 days. At 150 microgram/ml cell growth was completely inhibited by both compounds. Growth of cells was stimulated at 5 microgram/ml, by HBB at 4 and 8 days, and FF-1 at 8 and 12 days. HCB was compared with HBB and FF-1 for cell growth toxicity at 37 and 75 microgram/ml. At 75 microgram/ml, HCB was more toxic than HBB and FF-1 during the entire time period. At 37 microgram/ml, HCB was more toxic than HBB and FF-1 at 4 and 8 days. Cells seeded at high densities and treated with HBB for three days lost the high degree of postconfluence inhibition of cell division observed in control cultures. Cells treated with FF-1 for three days did not adhere well to the plastic growth surface. Ultrastructural features of the HBB- and FF-1-treated cells included decreased surface villi and increased lysosomes relative to the control cells.

Animals↗
PubMed1978

Comparative mutagenicity and toxic effects of 2,5,2',5'-tetrachlorobiphenyl and its metabolites in bacterial and mammalian test systems.

The possible toxicological properties of 2,5,2',5'-tetrachlorobiphenyl (TCB), 4-hydroxy-2,5,2',5'-tetrachlorobiphenyl (TCB-OH), and 2,5,2',5'-tetrachlorobiphenyl-3,4-oxide (TCB-oxide) were evaluated in three bioassay systems. Incubation of rat hepatocyte plasma membranes with 50 microgram/ml of TCB-OH decreased the activity of Mg2+-ATPase by approximately 90%, whereas approximately half of the enzyme activity remained after the TCB or TCB-oxide treatment. All three compounds were found to be inactive in the Salmonella/microsome mutagenicity assay. Only TCB-OH possessed potent cytotoxic activity against all four S. tymphimurium strains tested. It affects the viability of TA 1537 by as much as 40% even at concentrations as low as 1 microgram/ml. These data suggest the potential toxicological significance of metabolic activation by the hepatic microsomal mixed-function oxidases.

Adenosine Triphosphatases↗