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Biomedical subjects

M L Tang

Publications and source records attributed to M L Tang.

13 recordsLinked to original sources
PubMed1996

CD22 is both a positive and negative regulator of B lymphocyte antigen receptor signal transduction: altered signaling in CD22-deficient mice.

B cell activation following antigen receptor cross-linking can be augmented in vitro by ligation of cell surface CD22, which associates with the SHP1 protein tyrosine phosphatase. The targeted deletion of CD22 in mice demonstrated that CD22 differentially regulates antigen receptor signaling in resting and antigen-stimulated B lymphocytes. B cells from CD22-deficient mice exhibited the cell surface phenotype and augmented intracellular calcium responses characteristic of chronically stimulated B cells, as occurs in SHP1-defective mice. Thus, CD22 negatively regulates antigen receptor signaling in the absence of antigen. However, activation of CD22-deficient B lymphocytes by prolonged IgM cross-linking resulted in modest B cell proliferation, demonstrating that CD22 positively regulates antigen receptor signaling in the presence of antigen.

Animals↗
PubMed1996

Identification of immune system and response genes, and novel mutations causing melanotic tumor formation in Drosophila melanogaster.

We are using Drosophila as a model system for analysis of immunity and tumor formation and have conducted two types of screens using enhancer detector strains to find genes related to these processes; genes expressed in the immune system (type A; hemocytes, lymph glands and fat body) and genes increased in expression by bacterial infection (type B). For type A, tissue-specific reporter gene activity was determined. For type B, a variation of enhancer detection was devised in which beta-galactosidase is assayed spectrophotometrically with and without bacterial infection. Because of immune system involvement in melanotic tumor formation, a third type was hypothesized to be found among types A and B; genes that, when mutated, have a melanotic tumor phenotype. Enhancer detector strains (2800) were screened for type A, 900 for B, and 11 retained for further analysis. Complementation tests, cytological mapping, P-element mobilization, and determination of lethal phase and mutant phenotype have identified six novel genes, Dorothy, wizard, toto, viking, Thor and dappled, and one previously identified gene, Collagen IV. All are associated with reporter gene expression in at least one immune system tissue. Thor has increased expression upon infection. Mutations of wizard and dappled have a melanotic tumor phenotype.

Animals↗
PubMed1995

Exact power computation for dose-response studies.

The toxicity of an agent or the therapeutic effect of a drug may be assessed by a dose-response study. We present a method for computing the exact power of exact and large sample statistical tests employed for binary response data from such a study. This method, based on recursive polynomial multiplications, enables fast computation of exact power for studies with up to a moderately large sample size. We demonstrate the efficiency of our method using three examples. The method is suitable for the design and power analysis of dose-response studies in which the usual asymptotic approximations are suspect.

Adenoma↗
PubMed1995

Interleukin-4 and interferon-gamma production in atopic and non-atopic children with asthma.

Previous studies have demonstrated increased production of interleukin-4 (IL-4) and reduced production of interferon (IFN)-gamma in stimulated peripheral blood mononuclear cell cultures from children and adults with atopic dermatitis, however, it is unclear whether such an imbalance of cytokine production relates to other childhood atopic diseases such as asthma, and in particular to the presence of the atopic state per se. The production of IL-4 and IFN gamma in phytohaemagglutin- (PHA)-stimulated peripheral blood mononuclear cell (PBMC) cultures from atopic and non-atopic children with moderately severe chronic persistent asthma, and a group of age-matched non-atopic controls who did not have asthma was examined. Atopic children with asthma produced significantly more IL-4 and less IFN gamma than non-atopic children with asthma and non-atopic controls who did not have asthma. There was no significant difference in IL-4 or IFN gamma production between non-atopic children with asthma and controls. These findings demonstrate that an imbalance of IL-4 and IFN gamma production is present in atopic asthma as previously documented in atopic dermatitis, therefore suggesting that it is a feature of the atopic state per se.

Asthma↗
PubMed1995

Ontogeny of IL4 production.

There is evidence to suggest that the production of some cytokines in childhood is different to that in adults. The production of IL4 in PHA-stimulated PBMC cultures was examined in healthy neonates, children and adults to determine the ontogeny of IL4 production throughout childhood. In vitro IL4 production was found to be significantly reduced in neonates and children under 10 years of age as compared to adults, and to increase progressively with age. The mechanisms leading to reduced IL4 production in neonates were shown to be different to those in children, with a defect in signal transduction demonstrated for lymphocytes from neonates but not children < 10 years. The presence of an inhibitory factor in cord blood plasma was also noted. These age-dependent variations in IL4 production and response to stimulation with PMA/Ca may reflect differences in naive and memory T cell populations.

Adolescent↗
PubMed1994

Reduced interferon-gamma secretion in neonates and subsequent atopy.

Low interferon-gamma (IFN-gamma) secretion has been found in individuals with active atopic disease. Whether this is a cause or result of the disease process is uncertain. Cord blood IFN-gamma secretion was examined in 35 neonates who were then prospectively followed up for 1 year for the development of atopic disease. Infants who developed either symptoms of atopic disease or a positive IgE-mediated skin prick test at 12 months of age produced significantly less IFN-gamma at birth compared with those who did not (p = 0.005). This reduced secretion of IFN-gamma at birth indicates that the defect in interferon secretion is a primary component of the atopic state rather than an effect of the disease process.

Breast Feeding↗
PubMed1994

Efficient power computation for exact and mid-P tests for the common odds ratio in several 2 x 2 tables.

When designing a study that may generate a set of sparse 2 x 2 tables, or when confronted with 'negative' results upon exact analysis of such tables, we need to compute the power of exact tests. In this paper we provide an efficient approach for computing exact unconditional power for four exact tests on the common odds ratio in a series of 2 x 2 tables. These tests are the traditional exact test; a test based on a probability ordering of the sample space; and two tests based on ordering the sample space according to distance from the mean, or median. For each test, we consider both a conservative version and a mid-P adjusted version. We explore three computational options for power determination: exact power computation, calculation of exact upper and lower bounds for power, and Monte Carlo confidence bounds for power. We present an interactive program implementing these options. For study design, the program may be run several times to arrive at a sample configuration with adequate power.

Case-Control Studies↗
PubMed1994

Reduced interferon-gamma (IFN-gamma) secretion with increased IFN-gamma mRNA expression in atopic dermatitis: evidence for a post-transcriptional defect.

Reduced secretion of IFN-gamma in atopic individuals has been implicated in the pathogenesis of disease, though the mechanisms leading to this reduced secretion have not been elucidated. As production of IFN-gamma has been shown to be predominantly regulated by its rate of transcription, expression of IFN-gamma mRNA was examined in atopic children and in age-matched, non-atopic controls by polymerase chain reaction (PCR)-assisted mRNA amplification. Children with atopic dermatitis were found to have constitutive expression of IFN-gamma mRNA in freshly isolated peripheral blood mononuclear cells (PBMC) and in unstimulated PBMC cultures which increased further following stimulation with phorbol myristate acetate (PMA)/Ca in vitro. In contrast, expression of IFN-gamma mRNA in controls was only detected in stimulated cultures, as has been demonstrated previously for normal adults. These findings demonstrate that circulating T cells from atopic children have been activated in vivo, and suggest that T cell activation is a significant component of the inflammatory process in atopic dermatitis. Although expression of IFN-gamma mRNA was increased in the atopic children, secretion was confirmed to be significantly lower than in controls, indicating that the defect(s) underlying reduced IFN-gamma secretion in these individuals lie post-transcriptionally.

Base Sequence↗
PubMed1994

Spontaneous expression of IL-4 mRNA in lymphocytes from children with atopic dermatitis.

Normal lymphocytes do not generally produce or secrete lymphokines in the resting or unstimulated state and only express or release cytokines following activation. Recently, the spontaneous production of intracellular interferon-gamma (IFN-gamma) and spontaneous secretion of IL-6 has been documented in patients with atopic dermatitis. These findings indicated that lymphocytes had been previously activated in vivo. Such in vivo activation may also be associated with spontaneous production of IL-4. As measurement of IL-4 secretion by immunoassay is complicated by poor sensitivity, and only provides information on the net amount of cytokine present after secretion, adsorption, consumption and degradation have occurred, IL-4 mRNA expression in peripheral blood lymphocytes from children with atopic dermatitis and controls was examined by polymerase chain reaction (PCR)-assisted mRNA amplification. Spontaneous expression of IL-4 mRNA was detected in four of eight patients with severe atopic dermatitis. Following stimulation in vitro, seven of eight atopic patients demonstrated detectable IL-4 mRNA. In comparison, no spontaneous expression of IL-4 mRNA was found in controls, and only six of 10 controls expressed IL-4 mRNA in stimulated cultures. The spontaneous expression of IL-4 mRNA in unstimulated cultures from children with atopic dermatitis supports the possibility that previous in vivo activation has occurred, and suggests that IL-4 production is increased in vivo in atopic dermatitis. This in vivo activation together with the constitutive expression of IL-4 mRNA are likely to contribute to the spontaneous in vitro production of IgE in atopic patients.

Base Sequence↗
PubMed1993

The sartorius myocutaneous island flap.

The vascular supply to the distal part of sartorius m. was studied in 37 limbs by dissection under magnification and after black ink and latex injections. The muscle or myocutaneous island flap pedicled on the saphenous artery (SA) is supplied by a retrograde circulation through anastomoses of the SA with the perforating branches of the posterior tibial artery and the medial inferior genicular artery. Three different vascular patterns were defined. Retrograde injection also showed good perfusion of the SA. The flap is useful for covering around the knee, the proximal and middle thirds of the lower leg, and the end of the amputation stump. Raising of the flap has not resulted in any functional or cosmetic defect. Eighteen operations have so far been performed, six using the muscle island flap and twelve using the myocutaneous island flap, and all survived completely.

Humans↗
PubMed1993

Growth hormone deficiency and combined immunodeficiency.

The first description of an association of isolated growth hormone deficiency (IGHD) and combined immunodeficiency is presented. The findings suggest that IGHD should be considered as a cause of short stature in children with combined immunodeficiency before attributing growth retardation to infection.

Child, Preschool↗