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J R Seed

Publications and source records attributed to J R Seed.

At least 37 records · Page 2Linked to original sources
PubMed1994

Characterization of human serum-resistant and serum-sensitive clones from a single Trypanosoma brucei gambiense parental clone.

A protocol was developed to select clones of Trypanosoma brucei gambiense having different levels of resistance to normal human serum. Human serum-resistant clones were selected from a single parental clone by continuous serum treatment of infected immunosuppressed mice. Human serum-sensitive revertant clones were also obtained by continuous passage of resistant clones in immunosuppressed mice but without human serum pressure. It has been demonstrated that our trypanosome clones express distinct but stable levels of resistance. The variant antigenic type of each clone was characterized serologically and by 1-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. After selective pressure with human serum, variant antigen-type differences always occurred among clones in which different human serum susceptibilities were found. The work reported here demonstrates that in our T. brucei gambiense immunosuppressed mouse model there is a predictable association between variant antigen type and human serum resistance.

Animals↗
PubMed1993

Trypanosoma brucei rhodesiense: the inhibition of HL-60 cell growth by the African trypanosomes in vitro.

Trypanosomiasis is of major public health importance in Africa where the disease affects man and livestock. In order to explore the underlying mechanisms of pathogenesis in African trypanosomiasis, we studied the inhibition of host cell (human promyelocytic HL-60 cells) growth by Trypanosoma brucei rhodesiense using an in vitro system. This inhibition was not due to changes in pH or nutritional depletion of the culture medium by the trypanosomes as inhibitory activity was still observed in cultures that had been supplemented with glucose or fresh culture medium. Our study suggests that the African trypanosomes produce a soluble factor which inhibits the growth of HL-60 cells. This growth inhibitor does not appear to kill the HL-60 cells as determined by the trypan blue dye exclusion test. The production of this factor does not require host cell contact nor does it require a host cell cofactor. The trypanosome growth inhibitor is strictly a trypanosome product. Estimation of the molecular weight of the trypanosome growth inhibitor with Amicon filters revealed that the factor is greater than 30,000 Da in size. Protease and heat treatment of the factor resulted in the depletion of inhibitory activity. These results indicate that the African trypanosomes produce a large-molecular-weight protein growth inhibitory factor which could play a role in the pathogenesis of the disease.

Animals↗
PubMed1993

Relationship between human serum trypanocidal activity and host resistance to the African trypanosomes.

Results reported here show that humans have various levels of trypanocidal activity in their sera. This difference appeared stable when different samples were taken from the same individuals over time. It was not possible to account for the variability between individuals by obvious differences in health, nutrition, or living habits. In addition, the trypanocidal titers did not vary significantly when stored for various lengths of time at -70 C. To examine the relationship between the titer of trypanocidal activity in a host and the degree of human serum resistance of the challenge trypanosome inoculum, mice (C57BL/6J) were pretreated with various amounts of different human serum and then infected with clones having different degrees of resistance to human serum. It was demonstrated that host susceptibility to an African trypanosome infection depends upon 2 variables: the level of trypanocidal activity in individual human serum and the degree of human serum resistance of individual clones of African trypanosomes. Based upon the animal model presented here, it is hypothesized that this relationship is under selective evolutionary pressure and will influence the susceptibility of animals in endemic areas as well as the transmission of human trypanosomiasis.

Adolescent↗
PubMed1992

Intestinal parasites among North Carolina migrant farmworkers.

OBJECTIVES: The public health significance of intestinal parasitism among migrant farmworkers has been poorly defined. We report a three-part study in which we attempted to provide population-based estimates and identify risk factors for infection. METHODS: Parasite prevalence and incidence were estimated from two cross-sectional studies and a longitudinal study. We used questionnaires and clinical measurements such as hematocrits to examine risk factors and health effects. RESULTS: In the 1987 convenience sample (n = 265), parasite prevalence ranged from 28% among the US born to 86% among the Central American born, with no significant difference between the prevalence of pathogens among US-born (14%) and Mexican-born (24%) subjects (P = .12, chi 2 test). High prevalences were also found in the 1988 random sample. An annual incidence of 9.5% (n = 74) was demonstrated in 1988. Symptoms such as abdominal pain were associated with infection, and lower hematocrits were associated with hookworm infection (P = .02, t test). CONCLUSIONS: Infection with intestinal parasites appears to be an occupational hazard of farmwork, necessitating improved working and living conditions and greater clinical awareness.

Adolescent↗
PubMed1991

The epidemiology of tuberculosis among North Carolina migrant farm workers.

Although tuberculosis (TB) has been recognized as a significant health problem of migrant farm workers, the nature and extent of the problem have been poorly defined. We report the first population-based study of TB in a random sample of farm workers (n = 543) and the first use of recall antigens in an epidemiologic study of TB. Purified protein derivative positivity ranged from 33% in Hispanics to 54% in US-born blacks and 76% in Haitians. Active tubercular disease occurred in 3.6% of US-born blacks and 0.47% of Hispanics. Among US-born blacks, risk factors associated with farm work were most significant. Blacks born in the United States also had the highest prevalence of anergy. The use of recall antigens made possible a better description of the epidemiology of TB by excluding false negatives and clarifying associations between infection and risk factors. We conclude that TB among farm workers represents a serious public health problem with previously unrecognized risk factors. Additional resources for migrant health care, improvements in health care access, and fundamental changes in the system of migrant labor are all necessary to reduce the transmission of TB.

Agriculture↗
PubMed1991

Tissue alterations in Microtus montanus chronically infected with Trypanosoma brucei gambiense.

Changes in liver, spleen, kidneys, heart, and brain are reported for Microtus montanus chronically infected with Trypanosoma brucei gambiense. An increase in body weight of infected animals was attributable to a significant increase in total mass of spleen, liver and kidney. Cellular infiltrate consisting primarily of lymphocytes and plasma cells was observed in all organs and was particularly evident in intralobular connective tissue of the liver, adipose tissue of the hilum, and adjacent medullary region of the kidney, spleen, and the meninges. Disruption of normal metabolism and the pathological changes observed in liver and kidney suggest that the survival of trypanosome-infected voles is dependent largely on the physiological response occurring in these organs.

Animals↗
PubMed1989

African trypanosomes: inheritance of factors involved in resistance.

The C3HeB/FeJ mouse strain has a shorter survival time and is therefore more susceptible to a Trypanosoma brucei rhodesiense infection than the B10.BR/SgSnJ strain. The work reported here demonstrated that survival time is inherited as a recessive trait, whereas the ability to produce antibody to the first variant antigen population is inherited as a dominant trait. It was therefore not possible to correlate survival time with the ability to produce antibody in the F-1 and F-2 offspring. Both characteristics appeared to be multigenic. In addition, it was not possible to link the ability of an animal to control its early parasitemia, or its change in hematocrit, with either antibody production or survival time. The work strongly suggests that the increased survival time of the B10.BR/SgSnJ mouse is due at least partially to nonspecific but unidentified factors which do not segregate with VSG-specific immune responses. These nonspecific factors could include differences in susceptibility to toxic trypanosome catabolites.

Animals↗
PubMed1989

Nature of the trypanocidal factor in human serum.

The chemical nature of the trypanocidal factor in human serum was investigated. The results show that although the trypanocidal factor is contained within the high density lipoprotein (HDL) fraction of human serum, it is apparently not one of the major apolipoproteins of the HDL complex such as apolipoprotein A-I, A-II, or apolipoprotein B. The factor would appear to be a minor component of the HDL fraction whose chemical nature is still uncertain.

Animals↗
PubMed1988

Immune response to minor variant antigen types (VATs) in a mixed VAT infection of the African trypanosomes.

It has been shown that soon after the onset of acute infection with Trypanosoma brucei gambiense, mice are able to detect immunologically small numbers of minor variant antigen types (VATs) within the population. However, in more longstanding infections, considerably larger populations of minor VATs are required to stimulate an effective immune response. As a result, larger populations of minor VATs evade immune detection and, following a decrease in parasitaemia, become part of the relapse population. We hypothesize that the development of immunosuppression increases the effectiveness of antigenic variation as an escape mechanism.

Animals↗
PubMed1988

Growth of pleomorphic Trypanosoma brucei rhodesiense in irradiated inbred mice.

It was shown that irradiation (650 rad) of 7 inbred strains of mice did not block the ability of Trypanosoma brucei rhodesiense to transform from the long slender (LS) to the short stumpy (SS) form or alter the plateau in parasitemia. In addition, it was observed that significant differences in parasitemia levels, in the rate of transformation from the LS to the SS form, as well as in the survival times occurred between the irradiated C3HeB/FeJ and several of the other strains. These differences in the nonspecific ability to control parasitemia appeared to be characteristic for each inbred strain of mice. The resistant strains generally had lower parasitemia than the susceptible strains. However, it was also shown that there is not a one-to-one correlation between the innate ability of a mouse strain to control its initial parasitemia, and the strain's ability to clear the parasitemia or increase its survival time. It was therefore concluded that the hypothesis which states that the ability of an animal to increase nonspecifically the rate of transformation, and therefore to lower the parasitemia, allowing intact animals to respond immunologically and survive longer is either incorrect or incomplete. The results further show that the ability of mice to clear their initial parasitemia by an antibody response is not necessarily correlated with their survival time. Therefore, this study suggests that factors other than an antibody response and the nonspecific control of parasitemia are important in resistance.

Animals↗
PubMed1988

Changes in albumin levels in blood and urine of Microtus montanus chronically infected with Trypanosoma brucei gambiense.

Serum albumin and glucose concentrations and urinary excretion of alpha-keto acids and proteins were determined in samples obtained throughout a chronic Trypanosoma brucei gambiense infection in Microtus montanus. An increase in urinary excretion of alpha-keto acids and proteins during the terminal stage of disease was accompanied by a decrease in serum glucose concentration. This terminal hypoglycemia reflected a depletion of liver glycogen in most animals. In contrast (and the major focus of this study) serum albumin concentration was decreased by the second week of infection and in the final sample obtained was less than 50% of that measured in preinfection samples. Female animals survived approximately 1 wk longer than males and were less susceptible during the acute phase of disease. This relative resistance was most likely due to the fact that female animals were relatively more efficient in limiting parasitemia during the first week of infection. The similarity between humans and voles in terms of protein and alpha-keto acid excretion and changes in serum concentrations of glucose and albumin during trypanosome infection further validate the use of Microtus as an experimental model for trypanosomiasis in humans.

Albuminuria↗
PubMed1987

Further biochemical characterization of chronic Trypanosoma brucei gambiense-Microtus montanus infection.

Tyrosine aminotransferase (TAT), glutamic-pyruvic transaminase (GPT), glutamic-oxaloacetic transaminase (GOT), and alkaline phosphatase (ALP) were measured in the serum and livers of Microtus montanus infected with Trypanosoma brucei gambiense. Only liver TAT and serum ALP showed significant changes. In addition, blood glucose, pyruvate and lactate, and liver glycogen levels were assayed. All four compounds showed significant changes, strongly suggesting increased glycogen mobilization and increased catabolic activity. Interestingly, the serum ketone levels were very low and no significant changes were observed. These chronically infected animals had an organic aciduria in which pyruvate, lactate, beta-hydroxybutyrate, alpha-ketoglutarate, phenylpyruvate, and p-hydroxyphenylpyruvate were significantly increased. The possible significance of these observations is discussed.

Alkaline Phosphatase↗
PubMed1985

Multiple alpha-keto aciduria in Microtus montanus chronically infected with Trypanosoma brucei gambiense.

Microtus montanus chronically infected with a monomorphic strain of Trypanosoma brucei gambiense excreted in urine greatly elevated quantities of not only the aromatic alpha-keto acids, phenylpyruvic and 4-hydroxyphenylpyruvic acids, but also two aliphatic alpha-keto acids, pyruvic and alpha-ketoglutaric acids. Elevated keto acid excretion began approximately midway through infection and quantities remained elevated until death. Daily keto acid excretion did not correlate with daily parasitemia. Thus, a large metabolic disturbance exists in laboratory animals infected with African trypanosomes. The multiple alpha-keto aciduria potentially contributes to the pathogenesis of chronic African trypanosomiasis.

Animals↗
PubMed1984

Increased urinary excretion of aromatic amino acid catabolites by Microtus montanus chronically infected with Trypanosoma brucei gambiense.

Microtus montanus infected with Trypanosoma brucei gambiense for 16 and 21 days excreted significantly greater quantities of several aromatic amino acid catabolites when compared to uninfected control animals. Very large quantities of three aromatic alpha-keto acids (alpha-oxocarboxylic acids), phenylpyruvic acid, 4- hydroxyphenylpyruvic acid and indole-3-pyruvic acid, were excreted by infected animals. Increased excretion of indole-3-lactic acid and indole-3-acetic acid was also detected. Gas chromatographic-mass spectral analysis of the trimethylsilyl derivatives of phenylpyruvic acid, 4- hydroxyphenylpyruvic acid and indole-3-pyruvic acid confirms the identity of the aromatic alpha-keto acids elevated during infection. The marked alpha-keto aciduria indicates that a large disturbance exists in aromatic amino acid metabolism in this chronic animal model of African trypanosomiasis. The disturbance may contribute to the pathogenesis of the disease. The increased catabolite concentrations may also prove to be useful diagnostically and prognostically.

Amino Acids↗