PubMed Health⌕ Search

Biomedical subjects

T M Walker

Publications and source records attributed to T M Walker.

At least 37 records · Page 2Linked to original sources
PubMed1993

Ia- macrophages and cytokine networks contribute to tumor-induced suppression of CD4+ autoreactive T cells.

Tumor growth changes the functions and phenotypes of macrophages (M phi) and T cells. Suppression of CD4+ T cell autoresponses during tumor growth was contributed primarily by M phi. Tumor-induced alterations in the abilities of these cells to mediate autorecognition were assessed through syngeneic mixed lymphocyte reaction (SMLR) assays. Tumor-bearing host (TBH) M phi were significantly more suppressive (60-90%) than normal host (NH) M phi, and this suppression was caused partly by reduced Ia expression. TBH Ia- M phi were significantly more suppressive (50-80%) than their NH counterparts. The suppression mechanism was controlled partly by prostaglandin E2 (PGE2), because treating cultures with indomethacin and titrated NH and TBH Ia- M phi led to increased T-cell responsiveness, although responsiveness never reached levels of assays containing unseparated M phi. Blocking studies using anti-interferon-gamma (anti-IFN-gamma) monoclonal antibodies (mAb), anti-interleukin 4 (anti-IL-4) mAb, and indomethacin suggested that IFN-gamma, IL-4, and PGE2 contributed to tumor-induced M phi-mediated suppression. Our results suggested that a quantitative shift in M phi phenotype and a qualitative shift in M phi function in addition to differences in cytokine-directed accessory activities are partly responsible for tumor-induced suppression CD4+ T cell autoresponses.

Animals↗
PubMed1992

Macrophages stimulated by receptor-ligand interactions exhibit differences in cell-cycle kinetics during tumor growth: stimulation at Mac-1 and Mac-3 receptors alters DNA synthesis.

Phenotypic and functional changes associated with tumor-bearing host (TBH) macrophages (M phi) are partly responsible for immunosuppression during tumor growth. Flow cytofluorometric analyses revealed differences in cell-cycle kinetics between normal host (NH) and TBH M phi that were stimulated at specific receptors. Receptor-ligand interactions were induced by antibodies against Mac-1, -2, -3, and Ia receptors and changes in DNA synthesis were measured over a 12-h time course by incorporation of propidium iodide. TBH M phi showed higher DNA synthesis than NH M phi over this time course irrespective of the receptor induced. NH M phi stimulated at the Mac-1 receptor demonstrated higher DNA synthesis than control NH M phi although TBH M phi stimulated at this receptor and control TBH M phi failed to show any differences. Both NH and TBH M phi exhibited small, short-term decreases in DNA synthesis when stimulated at the Mac-2 receptor. TBH M phi that were stimulated at the Mac-3 receptor demonstrated higher DNA synthesis than their control counterparts while NH M phi stimulated at this receptor and control NH M phi showed identical levels of DNA synthesis. No differences in DNA synthesis were found among normal or TBH M phi that were stimulated through Ia. Differences in DNA synthesis did not appear to be attributable to differences in receptor expression. Further analysis of Mac-1 and Mac-3 stimulated cells revealed that DNA synthesis in NH M phi stimulated at the Mac-1 receptor returned to control levels at 48 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Cytokines and suppressor macrophages cause tumor-bearing host CD8+ T cells to suppress recognition of allogeneic and syngeneic MHC class II molecules.

Quantitative and qualitative tumor-associated changes in T cell phenotype and function were identified in CD8+ T cells. Tumor growth changed splenic CD4+/CD8+ T cell ratios and induced the appearance of more cells with the CD8+ phenotype. In comparison to equal concentrations of normal host (NH) counterparts, tumor-bearing host (TBH) CD8+ T cells were highly suppressive to allorecognition and autorecognition. Suppression was not due to quantitative reductions in CD4+ T cells, although minor qualitative differences were observed. Suppression appeared to be mediated partly by prostaglandin E2 (PGE2). Interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) contributed to TBH CD8+ T cell-mediated suppression. Blocking studies using monoclonal antibodies (mAb) in conjunction with indomethacin suggested that cytokine networks involving IFN-gamma, IL-4, and PGE2 were disrupted during tumor growth and promoted TBH CD8+ T cell suppression. Alloresponses and autoresponses were significantly suppressed when TBH CD8+ T cells mediated these reactions simultaneously with TBH Ia- macrophages. Inhibition of PGE2 production was unable to reverse the additive suppression caused by these two cell types. These results collectively suggest that tumor-induced changes in CD8+ T cells lead to suppressed allo-recognition and autorecognition through both soluble mediator molecules and cellular interactions.

Animals↗
PubMed1992

Impalpable breast lesions: marking of surgical specimens for pathology.

A simple method is described to indicate the abnormal area in breast biopsy specimens excised following mammographic localization of impalpable lesions. A hypodermic needle is inserted into the specimen through the abnormality immediately following specimen radiography, removing the need to radiograph individual tissue slices. The technique has proved successful in 121 out of 122 specimens.

Biopsy↗
PubMed1992

Tumor growth changes the contribution of granulocyte-macrophage colony-stimulating factor during macrophage-mediated suppression of allorecognition.

Tumor-bearing host (TBH) macrophages (M phi) suppress T cell alloresponses, and this study suggests granulocyte-macrophage colony-stimulating factor (GM-CSF), a molecule associated with suppressive M phi activity during tumor growth, signals more immunosuppression. In the absence of M phi, GM-CSF increased T cell proliferation in response to alloantigen. However, TBH M phi-mediated suppression of allorecogntion was further induced by GM-CSF. Allogeneic mixed lymphocyte reaction (MLR) cultures, containing normal host (NH) M phi, were either unaffected or enhanced. Prostaglandin E2 (PGE2), a highly suppressive monokine that decreases alloreactivity, did not seem to be involved in the suppression caused by the TBH M phi/GM-CSF interaction. M phi-CSF (M-CSF) addition to cultures did not reverse the suppression caused by TBH M phi and GM-CSF, and inhibition of PGE2 synthesis did not change the response to M-CSF. TBH Ia- M phi, a suppressor population that predominates among splenic M phi during tumor growth, demonstrated significantly lower reactivity in the presence of GM-CSF. In contrast, alloresponses suppressed by NH Ia- M phi demonstrated higher reactivity in the presence of GM-CSF. The data collectively suggest that TBH M phi respond differently to GM-CSF, and that tumor-induced changes in GM-CSF responsiveness affect M phi accessory ability.

Animals↗
PubMed1992

Lack of glyconeogenesis in pancreatic islets: expression of gluconeogenic enzyme genes in islets.

Studies were performed to obtain evidence for glyconeogenesis from pyruvate to the triose phosphates in pancreatic islets. Inability to show this evidence would be consistent with the fact that glyceraldehyde, but not pyruvate, is a potent insulin secretagogue. Synthesis of 14C-labelled glucose from 14C-labelled pyruvate could not be detected. Since this might have been due to lack of sensitivity required to measure 14C-glucose production in such a scarce tissue as islets, cDNA probes were used to estimate the relative expression of genes coding for gluconeogenic enzymes. Islets expressed pyruvate carboxylase mRNA, but even islets from rats which had been starved (a condition which induces phosphoenolpyruvate carboxykinase (PEPCK) in liver, kidney and adipose tissue) showed no PEPCK mRNA. This is consistent with our previous work showing the absence of PEPCK enzyme activity in islets. Therefore, islets can convert pyruvate to oxalacetate, but since they lack PEPCK, neither the beta nor alpha cell can convert oxalacetate to phosphoenolpyruvate and carry out glyconeogenesis. Pyruvate carboxylase mRNA was increased in islets that possessed the capacity for glucose-induced insulin release versus islets that lacked the capacity to respond to glucose, such as islets from fed rats (versus starved rats) and in islets cultured at a high concentration of glucose (versus at low glucose). Pyruvate carboxylase, therefore, must be involved in pyruvate metabolism and not glyconeogenesis in the pancreatic islet.

Animals↗
PubMed1992

Tumor growth changes responsiveness to and production of granulocyte-macrophage colony-stimulating factor during recognition of self MHC class II molecules.

Tumor growth decreases T-cell recognition of self major histocompatibility complex (MHC) class II molecules by inducing changes in splenic macrophage (M phi) phenotype and function. The current investigation shows tumor-induced alterations in autorecognition also are associated with changes in responsiveness to and production of granulocyte-M phi colony-stimulating factor (GM-CSF). In contrast to normal host (NH) M phi, tumor-bearing host (TBH) M phi failed to express higher MHC class II molecule density after exposure to GM-CSF. Autoreactive T cells stimulated by either NH or TBH M phi were suppressed by GM-CSF. Inhibition of prostaglandin E2 (PGE2) synthesis reversed M-CSF-induced suppression of autoreactivity to NH M phi and, to a lesser extent, to TBH M phi. When TBH autoreactive T cells were stimulated by TBH M phi, autoreactivity increased when GM-CSF was added and PGE2 synthesis was inhibited. Although GM-CSF can contribute to tumor-induced suppression, it did not affect the contribution of GM-CSF during autorecognition. Increased GM-CSF production was responsible, at least in part, for the TBH M phi-mediated suppression. Low concentrations of GM-CSF were produced endogenously by tumor isolates, and GM-CSF production was significantly increased when isolates were stimulated with lipopolysaccharide. Autoreactive T cells stimulated solely by TBH M phi produced more GM-CSF than autoreactive T cells stimulated by NH M phi. Cultures supplemented with several concentrations of NH or TBH M phi produced similar amounts of GM-CSF in a dose-dependent manner. Inhibition of PGE2 synthesis by NH and TBH M phi reduced GM-CSF production equally. Collectively, these results suggest that during tumor growth, responsiveness to and production of GM-CSF alters recognition of self MHC class II molecules.

Animals↗
PubMed1991

Glucose regulates leucine-induced insulin release and the expression of the branched chain ketoacid dehydrogenase E1 alpha subunit gene in pancreatic islets.

Much evidence has accumulated to support the idea that leucine can stimulate insulin release by allosterically activating glutamate dehydrogenase thus enhancing glutamate metabolism. It is less clear how the metabolism of leucine itself contributes to the signal for insulin release. We recently found that culturing pancreatic islets for 1 day at low glucose (1 mM) suppressed glucose-induced insulin release, but preserved leucine-induced insulin release. When islets were cultured at high glucose (20 mM), glucose-induced insulin release was preserved, but leucine-induced insulin release was suppressed (MacDonald, M. J., Fahien, L. A., McKenzie, D. I., and Moran, S. M. (1990) Am. J. Physiol., 259, E548-E554). The suppression of leucine-induced insulin release can be explained by glucose's suppression of the synthesis of the enzyme that catalyzes the first committed step of leucine metabolism, branched chain ketoacid dehydrogenase complex (BCKDH). High glucose suppressed the enzyme activity of the E1 component of the BCKDH complex, as well as the total activity of the BCKDH complex, to usually negligible levels in islets and decreased by an average of 90% the mRNA which encodes E1 alpha, the catalytic subunit of the E1 component of BCKDH, in islets and rat insulinoma cells. Time course studies showed that about 24 h in culture was required to maximally induce or suppress the expression of BCKDH E1 alpha. Culture at high glutamine with or without leucine mimicked to a lesser and more variable degree the effects of high glucose on leucine-induced insulin release and BCKDH E1 alpha mRNA. Leucine-plus-glutamine-induced insulin release was present after culture of islets with glucose and with or without any other secretagogue. Also, glutamate dehydrogenase transcripts and enzyme activity were not significantly altered by varying the concentration of glucose in the culture medium. Thus, leucine's insulinotropism via activation of glutamate dehydrogenase is constitutive. Preproinsulin mRNA levels were markedly increased at high glucose and glyceraldehyde phosphate dehydrogenase transcripts were either unaffected or slightly increased by glucose. Glutamine did not significantly effect the expression of genes other than BCKDH E1 alpha, and leucine had little or no effect on the expression of any of the four genes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Genetic diversity within Streptococcus mutans evident from chromosomal DNA restriction fragment polymorphisms.

Attempts to study the acquisition, transmission, and other aspects of the natural history of Streptococcus mutans infections in humans have been hampered by limitations and inconsistencies in methods by which phenotypic characteristics of individual isolates are examined. Because most mutans streptococci associated with human dental caries fall within the biotype I (serotypes c and f) grouping, designated S. mutans, these typing methods are of little value in distinguishing individual isolates. Here we show that strains of S. mutans obtained from over 30 individuals demonstrate unique "fingerprints" of chromosomal DNA digested with restriction endonuclease HaeIII. To demonstrate that this polymorphism in restriction fragments can be used to study the acquisition and transmission of this organism, we examined isolates of S. mutans from three mother-infant pairs obtained at the time the infant first became colonized by this organism. Results indicate that strains of S. mutans found in infants exhibit restriction fragment profiles identical to those of their mothers, strongly supporting the notion that mothers transmit this organism to their infants. Also, we show that strains of S. mutans with the same restriction fragment profile were stably maintained over a 3-year interval in the one mother-infant pair studied. Moreover, we found that mothers and their infants harbored only a few individual strains, suggesting that transmission of this organism is probably confined within discrete family cohorts. Collectively, these findings demonstrate the potential utility of genomic fingerprinting in studying the natural history of S. mutans infections in humans.

Bacteriocins↗
PubMed1988

The metacarpal index in homozygous sickle-cell disease.

The metacarpal index (MCI) was measured in 240 patients with homozygous sickle-cell (SS) disease and in 1082 normal persons constituting a comparison group. The MCI was greater in females than in males, but there appeared to be no significant difference between genotypes. Arachnodactyly may occur in some patients with SS disease, but there is no evidence of a genotype-related increase in metacarpal index.

Adolescent↗
PubMed1986

Pancreatoblastoma in a neonate with Wiedemann-Beckwith syndrome.

The association of pancreatoblastoma and Wiedemann-Beckwith syndrome has not been noted previously. In this report we describe a child with Wiedemann-Beckwith syndrome who had a pancreatoblastoma resected on day 27 of life. He is also the first reported case of Wiedemann-Beckwith syndrome in a black baby.

Beckwith-Wiedemann Syndrome↗
PubMed1981

Ultrasound of the gall bladder: experience in a district hospital.

In a retrospective survey performed to assess the reliability of ultrasound of the gall bladder in a district hospital the radiologists performing the examinations had little or no previous experience in non-obstetric ultrasound. In 142 patients who had the presence or absence of gall stones proved by surgery gall stones had been correctly predicted in 84% of patients with stones and absent in 64% of those without. This compares favourably with earlier reports from North America, and shows that ultrasound of the gall bladder is useful, even when staff experience is limited.

Cholelithiasis↗
PubMed1981

The chest radiograph in leptospirosis in Jamaica.

A consecutive series of 44 patients with proven leptospirosis was studied to document the radiographic pulmonary abnormalities, assess their prevalence, correlate them with the clinical signs and symptoms and determine their prognostic significance. Abnormalities were found in ten patients (23%), this prevalence being less than previously noted. The abnormalities shown were non-segmental opacification (consolidation-eight cases), basal linear opacities (collapse-five cases) and pleural effusions (four cases). The first radiographic demonstration of a large pleural effusion in leptospirosis is recorded. Non-jaundiced patients had a higher prevalence (43%) of these abnormalities than jaundiced (13%). No other correlation with clinical signs or symptoms was found. The presence of these abnormalities had no prognostic significance. It is concluded that the presence of radiographic pulmonary abnormality in in-patients with leptospirosis is common. These abnormalities are non-specific and can mimic other diseases leading to diagnostic difficulty. Such abnormalities may be extensive in the absence of clinical signs and symptoms.

Adolescent↗
PubMed1979

The normal metacarpal index.

Normal values for the metacarpal index (MCI) in British children and adults have been determined. In infancy before the appearance of the metacarpal epiphyses the index is constant up to about two years of age (5.2 in males and 5.5 in females). During childhood the index rises to reach a peak at about 16 years, and then falls slightly during adult life. The curves produced are almost identical to those previously found in black children, and one set of values may be used for children of either ethnic origin. The left hand should be used to calculate the MCI, and the results expressed as either below the mean for age, or in terms of percentile for age above the mean. Curves are presented showing percentile values. No attempt should be made to produce a clear distinction between normal and abnormal indices, but the percentile value used in conjunction with other clinical findings in the assessment of Marfan's syndrome and other skeletal conditions associated with arachnodactyly.

Adolescent↗
PubMed1978

Radiological evaluation of the cardiac apex in Jamaican children.

The position of the clinical apex beat projected on chest radiographs was compared to different points on the cardiac outline which have been regarded as the radiological apex. Good correlation was found between the clinical apex and the most lateral point of the left cardiac border, but not with the cardiophrenic angle or the lower end of the long diameter of the heart. The mid-clavicular line cannot be used to define the upper limit of the normal sized heart on radiographs as in clinical practice, because in many of the subjects the heart extended outside the mid-clavicular line.

Child↗
PubMed1978

The metacarpal index in Jamaican children and adults.

The metacarpal index was measured in radiographs of the hands of 615 male and 667 female Jamaicans aged over two years. The index increased with age from two years to adulthood, and was greater in females than in males, and greater in the left hand than the right hand. Means and standard deviations of the index for the left hand are presented as standards. An index of 9.6 for males and 10.1 for females over the age of 13 years is suggested as the upper limit of normal (three standard deviations above the mean). These standards are higher than those previously reported, and are probably applicable to other black populations outside Jamaica.

Adolescent↗