Biomedical subjects
Publications and source records attributed to J E Jones.
Giardiasis represents a major protozoan infection for the 1990s. This article reviews this organism for the primary care physician, discussing the characteristics, clinical manifestations, diagnosis, and treatment. Prevention and patient education needs are also presented.
Parasitic infection during pregnancy is common. With most parasites, primary prevention is very effective in avoiding infestation. With the exceptions of malaria, toxoplasmosis, and African trypanosomiasis, when infection does occur, treatment decisions should be based on the impact of the infection on the patient and her fetus on an individual basis. When treatment is indicated, selection of medications with the least potential to harm the mother and more particularly the developing fetus is essential.
A Crisis Team staffed by eight psychiatric nurses provided a 24-hour service to the seriously and chronically mentally ill who were experiencing psychiatric crisis. Immediate and continuing help was provided to patients and their relatives in their homes. Effects on patients, relatives and hospital admissions were studied. The sample consisted of 69 patients seen during a three-month study period. Six months later, 80% of patients and 73% of their relatives were interviewed by an independent psychologist. Of the sample, 80% had previous psychiatric admissions and were diagnosed as suffering from one of the functional psychoses--mainly schizophrenia or manic depression. The crises that led to the Team's interventions were mostly psychotic episodes and aggressive or suicidal behaviours; 47% occurred at night. Hospital records confirmed reports from staff, patients and relatives that the Team had halved admissions. Most patients and relatives were "very satisfied" with the treatment received from the Team and considered it had helped "greatly". They especially liked the home visits, the 24-hour availability and the friendly staff who provided them with support, medication and where needed, accommodation. In spite of the interventions of the Team, some 40% of patients were admitted during the research period, and at follow-up most were still experiencing symptoms and difficulties. Relatives, more than patients, expressed a need for additional rehabilitation and easier access to hospital, especially for those severely ill patients whom they found too difficult to live with. While the work of the Crisis Team proved highly beneficial for both patients and relatives, and reduced hospital admissions by half during the study period, it is clear that there is still a need for long-term support and rehabilitation.
Previous studies of murine T cell recognition of the pre-S(2) region of the hepatitis B surface Ag (HBsAg) identified high (H-2b,d,q), intermediate (H-2s,k), and low to nonresponder (H-2f) haplotypes. However, these studies utilized the y subtype of HBsAg. The purpose of this study was to examine the influence of viral subtype on T cell recognition of the pre-S(2) region and to identify specific T cell recognition sites in a panel of H-2 congenic strains. Immunization with pre-S(2) containing HBsAg particles of the d and y subtypes indicated that T cell recognition of the pre-S(2) region is predominantly subtype-specific in murine strains of eight different H-2 haplotypes. Furthermore, the B10.M strain (H-2f) classified as a T cell nonresponder to the y subtype of the pre-S(2) region responds efficiently to the d subtype, indicating that pre-S(2) responder status can be subtype-dependent as well as subtype-specific. Studies using a truncated pre-S(2) polypeptide and synthetic peptides illustrated that the C-terminal sequence (p148-174) of the pre-S(2) region is the dominant focus of T cell recognition in multiple murine strains. Specifically, 17 distinct T cell recognition sites were defined within the C-terminal half of the pre-S(2) region. The fine specificity of T cell recognition of the pre-S(2) region was dependent on the H-2 haplotype of the responding strain. T cell recognition of all 17 sites was subtype specific, which is consistent with the fact that the C-terminal sequence is highly polymorphic between the d and y subtypes of the pre-S(2) region. Lastly, it was shown that the ability of synthetic peptides to elicit T cells cross-reactive with the native pre-S(2) region was variable and depended on the nature of the immunizing peptide. The pre-S(2)-containing HBsAg vaccines currently in clinical trials are composed of ra single subtype, either d or y. The results of this study suggest that both subtypes should be incorporated to increase the frequency of T cell responders to the pre-S(2) region, and to insure Th cell memory relevant to infection with hepatitis B virus of either the d or y subtypes.
One purpose of this study was to examine the influence of viral subtype on in vivo antibody production to the pre-S(2) region of the hepatitis B surface Ag. Immunization with hepatitis B surface Ag particles containing the pre-S(2) region of the d or y subtypes identified the B10.M (H-2f) strain as an antibody nonresponder to the pre-S(2) and S regions after immunization with the y subtype, but as an antibody responder to the pre-S(2) and S regions after immunization with the d subtype. Both the S region and pre-S(2) region-specific antibody responses emanated from pre-S(2)/d-specific Th cell function because B10.M mice are T cell nonresponsive to the S region of both subtypes. Although responder/nonresponder status of the B10.M strain was dependent on the pre-S(2) subtype used for immunization, the anti-pre-S(2) antibody produced was totally cross-reactive on both subtypes. This is consistent with the conserved nature of the dominant pre-S(2) antibody-binding site and the highly polymorphic nature of the pre-S(2) sequence that represents the focus of T cell recognition. These data suggest that, to fully benefit from the inclusion of pre-S(2) region sequences, third generation hepatitis B virus vaccines should contain both the d and y subtype sequences of the pre-S(2) region to increase the frequency of pre-S(2) and S-specific antibody responses and to insure Th cell memory relevant to both viral subtypes. A second purpose of this study was to "design" a synthetic pre-S(2) immunogen based on combining the dominant B and T cell recognition sites into a single peptide. A composite peptide consisting of the dominant T cell recognition sequence p151-174 positioned N-terminal to the dominant B cell site p133-143 (i.e., p151-174(133-143] yielded an effective pre-S(2) synthetic immunogen. Interestingly, the orientation of the T and B cell determinants and the context of the T cell site within the larger composite peptide influenced both antibody fine specificity and T cell fine specificity.
In each of two experiments, the effect of inoculation of coagulase-negative staphylococci (C-NS) into the ovine mammary gland was studied. In the first experiment, ewes were inoculated with one of six different C-NS to study differences in the pathogenicity of the isolates. In the second, ewes were inoculated with Staphylococcus simulans to study the sequential histopathological features of the infection. The existence of subclinical mastitis was established by consistent isolation of bacteria, the demonstration of high somatic cell counts in milk and an inflammatory reaction in biopsy samples of mammary tissue. A variation in the pathogenicity of the different isolates was evident: one Staph. chromogenes isolate caused clinical mastitis, four Staph. simulans isolates caused subclinical mastitis and one Staph. xylosus isolate caused a transient increase of somatic cell counts. Neutrophilic infiltration was the predominant histopathological finding. Lysis of neutrophils, destruction of alveoli and, in late stages of the infection, infiltration of lymphocytes and fibrous tissue proliferation were also noted.
Infants born to hepatitis B virus carrier mothers, who express a secreted form of the nucleocapsid antigen designated HBeAg, invariably become persistently infected. To investigate the role of immunologic tolerance mechanisms in chronic infection of the newborn, we have generated HBeAg-expressing transgenic mice. HBeAg-expressing transgenic mice were tolerant to both HBeAg and the nonsecreted nucleocapsid (hepatitis B cor antigen/HBcAg) at the T-cell level. Transgenic mice did not produce antibody to HBeAg but did produce anti-HBc antibody in vivo and in vitro. The coexistence of tolerance to HBc/HBe T-cell determinants and anti-HBc antibody production in vivo parallels the immunologic status of neonates born to carrier mothers. It was also demonstrated that the maintenance of T-cell tolerance to HBcAg/HBeAg required the continued presence of the tolerogen and in its absence persisted for less than 16 weeks. The reversibility of T-cell tolerance to HBcAg/HBeAg may explain the inverse correlation between age of infection and rates of viral persistence. These observations suggest that a function of the HBeAg may be to induce immunologic tolerance in utero. Expression of HBeAg may represent a viral strategy to guarantee persistence after perinatal infection.
1. Male poults were fed diets with 50 and 100 mg supplemental niacinamide/kg and grown at stocking densities of 3.2 and 4.3 birds/m2 from 56 to 112 d. 2. At 50 mg/kg niacinamide high stocking density (HSD) depressed 112 d body weight and gain from 56-112d. High dietary niacinamide (100 mg/kg alleviated the growth depression under HSD but decreased body weight gain under low stocking density (LSD). 3. Dressed yield and hock width were not affected by dietary niacinamide or stocking density. 4. Dressed carcase composition was altered by stocking density. The dressed carcase of HSD birds contained 3.7% more protein and 7% less fat. 5. High dietary niacinamide tended to increase carcase protein (+2.4%) and decrease carcase fat (-4.0%).
This laboratory investigated the anabolic effect of the synthetic steroid trienbolone acetate (TA) and found it effective in male and female meat turkeys without any apparent gross abnormalities (Poultry Sci., 61: 1386, 1982). The present study was undertaken to characterize the response of female turkeys, fed equicaloric diets varying in dietary protein density to anabolic agents implanted at 13 wks. TA and zeranol (Z) were tested singly and in combination (TAZ). Body weight gain and feed conversion at 16 wks of age were improved (P less than 0.01) with TA and TAZ. The response to TA was enhanced as dietary protein density increased. Carcass fat, protein, ash, energy, potassium, and calcium were not altered by implant treatment. A trend existed toward increased carcass fat with zeranol implantation. Carcass moisture (P less than 0.01) and sodium (P less than 0.05) were increased in the TA treatment. Blood plasma electrolytes were not affected by implant treatments but plasma calcium was decreased (P less than 0.05) by TAZ. No synergism was noted between TA and Z with respect to growth, feed conversion, carcass composition, plasma electrolytes with the exception of plasma calcium. No interaction was observed between dietary protein density and implant treatment. Performance variables increased and carcass fat decreased with increasing dietary protein density. These results confirm our earlier finding with respect to TA and provide additional evidence that dietary protein density influences the response of meat turkeys to TA. The data show that zeranol lacks an anabolic effect in turkeys.
Expression of the N-ras oncogene under the control of the glucocorticoid-responsive promoter in the pheochromocytoma cell line UR61, a subline of PC-12 cells, has been used to investigate the differentiation process to neuronal cells triggered by ras oncogenes (I. Guerrero, A. Pellicer, and D. E. Burstein, Biochem. Biophys. Res. Commun. 150:1185-1192, 1988). Using ras-inducible cell lines, we observed that expression of the oncogenic N-ras p21 protein interferes with the ability of phorbol esters to induce downregulation of protein kinase C. This effect was associated with the appearance of immunologically detectable protein kinase C as well as the activity of the enzyme as analyzed either by binding of [3H]phorbol-12,13-dibutyrate in intact cells or by in vitro kinase activity. These results indicate a relationship between ras p21 and protein kinase C in neuronal differentiation in this model system. Comparison to the murine fibroblast system suggests that this relationship may be functional.
Two experiments were conducted to determine the effects of anticoccidial agents on production and reproduction of broiler breeders. In Experiment 1, nicarbazin (NCZ) was fed at 20, 50, and 100 ppm. There was no depression in egg production, egg weight, or fertility from feeding these levels. As level of NCZ increased, there was a linear decrease in hatchability. The amount of 4,4'-dinitrocarbanilide (DNC) in the egg yolks increased linearly as the levels of NCZ went up; the degree of egg-shell depigmentation was directly related to the level of NCZ fed starting at 50 ppm. Experiment 2 utilized a different strain of broiler breeders. Halofuginone (3 ppm), maduramicin (5 ppm), monensin (100 ppm), narasin (70 ppm), NCZ (125 ppm), robenidine (33 ppm), and salinomycin (60 ppm) were fed to broiler breeders at the levels listed. Only NCZ reduced egg production. Narasin induced a reduction in egg weight. Both narasin and salinomycin caused a significant drop in hatchability. Feeding NCZ also induced a rapid and more severe decrease in hatchability. Monensin was the only anticoccidial agent that reduced fertility. Halofuginone, maduramicin, and robenidine had no biologically significant effect on henday production, egg weight, hatch of fertile eggs, or shell depigmentation. Feeding NCZ at 125 ppm caused a complete bleaching of brown-shell eggs by the 3rd consecutive day of treatment; but 7 days after NCZ was withdrawn from the feed, pigmentation returned to the pretreatment level.
Two studies were conducted to determine the effects of anticoccidial agents on the production and reproduction of White Leghorns. In Experiment 1, nicarbazin (NCZ) was fed at 0, 20, 50, and 100 ppm. Hen-day egg production, egg weight, the egg-yolk DNC (4-4'-dinitrocarbanilide) level, and egg-yolk mottling were affected by the treatments. When response was evidenced, the relationship between those variables and the level of NCZ was basically linear. Decreased egg production occurred from Days 5 and 6 of the treatment through Days 1 and 2 of withdrawal. On Days 9 and 10 of treatment, the control hens peaked at 92% hen-day production, while hens fed 20, 50, and 100 ppm of NCZ peaked late--at 90, 82, and 80%, respectively. Compared to the controls, egg weight was reduced linearly as the level of dietary NCZ increased. The egg-yolk DNC level increased from Days 3 and 4 of treatment through Days 9 and 10 of withdrawal. Egg yolk mottling generally increased along with the level and duration of feeding NCZ. If the NCZ was mistakenly fed to White Leghorn layers, ill effects would be alleviated within 10 days after drug withdrawal. In Experiment 2, halofuginone (3 ppm), maduramicin (5 ppm), monensin (100 ppm), narasin (70 ppm), nicarbazin (125 ppm), robenidine (33 ppm), and salinomycin (60 ppm) were fed to White Leghorn hens at the levels specified in parentheses. Nicarbazin reduced egg production, depressed egg weight, reduced shell thickness, and caused egg-yolk mottling; but internal egg quality, as measured by Haugh Units, was unaffected. Halofuginone, maduramicin, monensin, narasin, robenidine, and salinomycin did not have a meaningful effect on the variables measured when fed to White Leghorn layers.
The response was determined of male poults to high levels of dietary niacinamide, when maintained in a stressful environment of high stocking density and high litter moisture induced by excess dietary NaCl. The experiment was designed as a factorial (2 by 2 by 2) with 70 versus 140 mg of niacinamide per kg; .3 versus 1% NaCl; 7 versus 14 birds per m2. Each treatment was assigned to 6 pens, with either 20 or 40 males per pen depending on stocking density. The calculated niacin content of the basal diet was 22 mg per kg; the experimental diets contained 92 and 162 mg of total niacin per kg. Added niacinamide at 140 mg per kg increased the body weight at 8 wk of age (3,095 versus 3,198) at .3% dietary NaCl. The response to 140 mg per kg of niacinamide was 4.6% at .3% NaCl and only 1.9% at 1% NaCl. The high level of niacinamide was ineffective in terms of alleviating the growth depression induced by a high stocking density. Treatment effects were not detected in relation to feed efficiency. The incidence of leg abnormalities was not influenced by dietary niacinamide or by litter moisture, but was aggravated by a high stocking density. The treatments did not induce ascites or macroscopic lesions in the heart or kidney. These findings demonstrated that supplemental niacinamide at 140 mg per kg, in a basal diet calculated to contain 22 mg of niacin per kg of feed, will produce a significant increase in the weight gain of male poults at 8 wk of age under praxis conditions when dietary salt is at .3%, but not at 1%.
The mechanisms that lead to the production of sensory hair cells during regeneration have been investigated by using 2 different procedures to ablate preexisting hair cells in individual neuromast sensory epithelia of the lateral line in the tails of salamanders, then monitoring the responses of surviving cells. In one series of experiments, fluorescent excitation was used to cause the phototoxic death of hair cells that selectively take up the pyridinium dye DASPEI. In the other experiments, the ultraviolet output of a pulsed neodymium-YAG laser was focused to a microbeam through a quartz objective lens in epi-illumination mode and used to selectively kill individual unlabeled hair cells while the cells were simultaneously imaged by transmitted light DIC microscopy. Through observation of the treated neuromasts in vivo, these experiments demonstrated that mature sensory epithelia that have been completely depleted of hair cells can still generate new hair cells. Preexisting hair cells are not necessary for regeneration. Immediately after the ablations the only resident cells in the sensory epithelia were supporting cells. These cells were observed to divide at rates that were increased over control values, and eventually those cell divisions gave rise to progeny that differentiated as hair cells, replacing those that had been killed. Macrophages were active in these epithelia, and their phagocytic activity had a significant influence on the standing population of cells. The first new hair cells appeared 3-5 d after the treatments, and additional hair cells usually appeared every 1-2 d for at least 2 weeks. We conclude that the fate of the progeny produced by supporting cell divisions is plastic to a degree, in that these progeny can differentiate either as supporting cells or as hair cells in epithelia where hair cells are missing or depleted.
Residues 120-131 within the hepatitis B core Ag (HBcAg) represent a dominant T cell recognition site for mice of the H-2S haplotype. This study was undertaken in order to identify residues within the p120-131 sequence which either interact with the TCR termed epitopic residues or interact with MHC class II molecules termed agretopic residues. For this purpose a panel of analogs of p120-131 composed of peptides containing single alanine substitutions for each residue was synthesized. These peptides were analyzed functionally for their ability to stimulate p120-131 or HBcAg-primed T cells and for their immunogenicity in B10.S or [B10.S X B10 (nonresponder)]F1 mice. Furthermore, analogs of p120-131 were used as stimulators and inhibitors of T cell activation in competitive inhibition experiments. Cumulatively these functional studies allowed us to identify residue 125 as a dominant epitopic residue and residues 127 and 129 as dominant agretopic residues. Furthermore, a p120-131 analog containing an alanine substitution for the dominant agretopic residue was immunogenic in B10.S mice, but was nonimmunogenic in (B10.S X B10)F1 mice indicating that T cell responsiveness is influenced by MHC class II gene dosage effects and can be inherited in an apparent recessive manner. In this study, critical residues involved in the immunogenicity of this dominant T cell determinant of HBcAg were defined, in a companion study, the influence of these residues on tolerogenicity was examined.
One purpose of this study was to examine the concept of T cell immunodominance employing a neonatal tolerance model. The extent to which a single T cell recognition site can represent the total T cell response to hepatitis B core Ag (HBcAg) was examined in the B10.S and B10 murine strains. It was shown that the entire B10.S T cell response to HBcAg was focused on a single immunodominant site represented by residues 120-131. This was demonstrated by exposing B10.S neonatal mice to p120-140 or p120-131, which resulted in a state of T cell tolerance to the entire HBcAg. In contrast, p120-140 contained an immunogenic T cell site for B10 mice, p129-140, but this site was nontolerogenic. Similarly, injection of p120-140 into (B10.S X B10)F1 neonatal mice resulted in tolerization of p120-131-specific, I-As-restricted T cells, but not of p129-140-specific, I-Ab-restricted T cells. The second purpose of this study was to attempt to explain the immunologic basis of an immunogenic yet nontolerogenic T cell determinant. It was shown that the p120-131 T cell site, which is immunogenic and tolerogenic in B10.S mice, could be converted into an immunogenic/nontolerogenic T cell site by a single amino acid substitution in either residue 127 or 129. Residues 127 and 129 were previously shown to be involved in interaction with MHC class II molecules (agretopic). These results demonstrated that the relative avidity of a peptide-MHC interaction can influence T cell tolerance induction. Furthermore, the results suggest that a higher threshold of peptide-MHC avidity may be required to induce T cell tolerance as compared to the threshold of peptide-MHC avidity required to immunize T cells.
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The NAD(P)H:menadione oxidoreductase gene (Nmo-1) codes for a quinone reductase (also called DT diaphorase; EC 1.6.99.2) believed to play a central role in protection against oxidative stress. We have studied mice with a radiation-induced chromosomal deletion involving the albino locus (c) on chromosome 7 and found that Nmo-1 mRNA levels and the rate of Nmo-1 gene transcription are markedly increased (greater than 100-fold and greater than 12-fold, respectively) in the untreated c14CoS/c14CoS deletion homozygote, compared with the untreated Cch/Cch wild-type and the Cch/C14CoS heterozygote. These data suggest that a gene located on chromosome 7 encodes a trans-acting regulatory factor that might be a negative effector of the Nmo-1 gene, which we show here is located on chromosome 8 approximately 1.4 centimorgans (about 1000 kilobase pairs) from the Es-2 gene. Conversely, there are no detectable basal levels of cytochrome P1450 (Cyp1a1 gene) or cytochrome P3450 (Cyp1a2 gene) mRNA, indicating that the regulation of basal expression of the Cyp1a1 and Cyp1a2 genes is distinct from that of the Nmo-1 gene. Moreover, the Cyp1a1 and Cyp1a2 genes and the Nmo-1 gene are induced by tetrachlorodibenzo-p-dioxin in the cch/cch, cch/c14CoS, and c14CoS/c14CoS mice. The mechanism of tetrachlorodibenzo-p-dioxin inducibility of the Cyp1a1, Cyp1a2, and Nmo-1 genes is, therefore, independent of the mechanism of Nmo-1 gene activation in untreated c14CoS/c14CoS mice.