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A Good

Publications and source records attributed to A Good.

At least 19 recordsLinked to original sources
PubMed2001

H-2D end confers dominant protection from IL-10-mediated acceleration of autoimmune diabetes in the nonobese diabetic mouse.

BALB/c mice that express IL-10 as a transgene in their pancreatic beta cells (Ins-IL-10 mice) do not develop diabetes, even after crossing to nonobese diabetic (NOD) mice ((Ins-IL-10 x NOD)F(1) mice). However, backcross of F(1) mice to NOD mice (NOD.Ins-IL-10 mice) results in N2 and N3 generations that develop accelerated diabetes. In this study, we found that NOD.Ins-IL-10 mice that expressed BALB/c-derived MHC molecules (NOD.Ins-IL-10(H-2(g7/d)) mice) were protected from diabetes. This protection associated with peri-islet infiltration and preserved beta cell function. Moreover, expression of I-A(d) and I-E(d) MHC class II molecules of BALB/c origin was not responsible for protection, but NOD.Ins-IL-10 mice that expressed BALB/c MHC class I D(d) molecules (NOD.Ins-IL-10(H-2(g7/d)) mice) did not develop diabetes. To directly test the possibility of a protective role of H-2D(d) in the development of accelerated diabetes, we generated transgenic mice expressing D(d) under the control of the MHC class I promoter. We found that double transgenic NOD.Ins-IL-10-D(d) mice developed accelerated diabetes in a fashion similar to NOD.Ins-IL-10 mice that were D(d) negative. Microsatellite analysis of H-2D(d)-linked loci confirmed association between BALB/c-derived alleles and protection of NOD.Ins-IL-10(H-2(g7/d)) mice. These results suggest a control of H-2D(d)-linked gene(s) on IL-10-mediated acceleration of autoimmune diabetes and dominant protection of the D(d) region in NOD.Ins-IL-10 mice.

Animals↗
PubMed2001

Molecular basis of the anaerobic response in plants.

The response of plants to flooding is complex and involves the induction of specific gene sets. A multidisciplinary approach by several research teams has led to a reasonably good understanding of the low oxygen response, and many of the genes and proteins that are involved are known. But the factors that are critical in determining tolerance or intolerance remain unknown. Microarray technology offers renewed hope to unravel the complex changes in gene expression occurring in plants upon low oxygen treatment and what mechanisms are involved in the response.

Adaptation, Physiological↗
PubMed2001

Structure-based virtual screening protocols.

Virtual screening techniques continue to play an important role within the pharmaceutical industry lead discovery process. A core element of these technologies encompasses the ability to virtually screen compound databases in three-dimensional (3-D) target active sites (structure-based virtual screening (SVS)). Reviewed are the latest developments within SVS, with particular emphasis on new technology and validation experiments. Examples of successful SVS application are highlighted, together with studies illustrating current technology limitations. New methods for scoring ligand-protein binding interactions are discussed, including the latest developments in ligand interaction sampling technology.

Computer Graphics↗
PubMed2000

Transcription factor expression during pancreatic islet regeneration.

Recent studies by a number of laboratories have identified transcription factors that are involved in pancreatic development. Indeed, marked abnormalities in pancreatic development result from deficiencies in these molecules, which include, among others, PDX-1, islet-1 (Isl-1), and Pax-6. These studies have prompted us to evaluate the expression of Isl-1 and Pax-6 in the pancreas of the interferon-gamma (IFNgamma) transgenic mouse, which exhibits new islet growth and expansion of ducts throughout the life of the animal. We have previously demonstrated that PDX-1 is strikingly expressed in the ducts of the IFNgamma transgenic mouse. This latter observation compelled us to examine expression of hepatocyte nuclear factor-3beta (HNF3beta), which mediates PDX-1 gene transcription, in the IFNgamma transgenic pancreas as well. As a result of these studies, we now demonstrate marked expression of these transcription factors in the pancreatic ducts of IFNgamma transgenic mice. These data suggest a role for these transcription factors during pancreatic regeneration in the IFNgamma transgenic mouse.

Animals↗
PubMed2000

IFN-gamma overexpression within the pancreas is not sufficient to rescue Pax4, Pax6, and Pdx-1 mutant mice from death.

In the presence of interferon-gamma (IFN-gamma), pancreatic ductal epithelial cells grow continuously, and islets undergo neogenesis. To determine whether these new islets are derived from conventional precursors, we tested whether IFN-gamma can complement the loss of transcription factors known to regulate pancreatic development. We analyzed the effect of a transgene on lethality in mice lacking the transcription factors Pax4, Pax6, or Pdx-1, by intercrossing such mice with transgenic mice whose pancreatic cells make IFN-gamma (ins-IFN-gamma mice). However, IFN-gamma expression did not rescue these mice from the lethal mutations, because no homozygous knockout mice carrying the IFN-gamma transgene survived, despite the survival of all other hemizygous gene combinations. This outcome demonstrates that the pathway for IFN-gamma regeneration requires the participation of Pax4, Pax6, and Pdx-1. We conclude that the striking islet regeneration observed in the ins-IFN-gamma NOD strain is regulated by the same transcription factors that control initial pancreatic development.

Animals↗
PubMed2000

Expression of ErbB receptors during pancreatic islet development and regrowth.

We have characterized expression of the ErbB receptor family and one of its ligands, heregulin, in an effort to identify molecules associated with pancreatic development and regeneration. In addition to studying expression during fetal pancreatic development, we have also studied expression during pancreatic regeneration in the interferon-gamma (IFNgamma)-transgenic mouse, which exhibits significant duct cell proliferation and new islet formation. These studies demonstrate significant expression of the ErbB2, ErbB3, and ErbB4 receptors, in addition to heregulin isoforms, in the developing murine fetal pancreas. We also report significant ductal expression of these proteins during IFNgamma-mediated pancreatic regeneration. This striking expression was absent in 1-week-old neonates, but was clearly visible in pups by 5 weeks of age. These data therefore indicate that ErbB receptor and ligand expression decline by birth in both the IFNbeta-transgenic and non-transgenic mice, and that expression resumes early in postnatal life in the IFNbeta-transgenic mice. The expression of ErbB receptor family members at sites of islet development and regrowth suggests that these molecules might be relevant to these processes.

Animals↗
PubMed1999

Micronized progesterone: clinical indications and comparison with current treatments.

OBJECTIVE: To integrate and evaluate the pharmacokinetic, endocrine, and clinical effects of micronized progesterone formulations. DESIGN: Published articles concerning the pharmacokinetics of orally administered progesterone and the potential clinical uses of oral micronized progesterone were reviewed. Results concerning their use for secondary amenorrhea, premenopausal bleeding disorders, luteal phase dysfunction, termination of premature labor, hormone replacement therapy, and premenopausal syndrome are summarized. Critical issues to be resolved through ongoing preclinical and clinical research are highlighted. RESULT(S): Because of the enhanced bioavailability of oral micronized progesterone, the compound may be useful for a variety of therapeutic indications. Oral micronized progesterone is available in France, and a formulation recently has been approved in the United States for the treatment of secondary amenorrhea and postmenopausal hormone replacement therapy. A large body of evidence, including the Postmenopausal Estrogen/Progestin Interventions study, suggests that the use of a combination of estrogen and oral micronized progesterone is optimal for long-term hormone replacement therapy. There also are data indicating that oral micronized progesterone could be of potential use for the treatment of premenopausal bleeding disorders, luteal phase disorders, and premature labor. CONCLUSION(S): Oral micronized progesterone has widespread clinical potential, particularly for the treatment of secondary amenorrhea and dysfunctional premenopausal bleeding, and as a component of postmenopausal hormone replacement therapy.

Amenorrhea↗
PubMed1999

PDX-1 and Msx-2 expression in the regenerating and developing pancreas.

We have observed pancreatic duct cell proliferation and islet regeneration in transgenic mice whose pancreata produce interferon gamma (IFNg mice). We have previously demonstrated that new islet cells derive from endocrine progenitor cells in the pancreatic ducts of this model. The current study was initiated to define these endocrine progenitor cells further and to identify novel markers associated with pancreatic regeneration. Importantly, we have found that PDX-1, a transcription factor required for insulin gene transcription as well as for pancreatic development during embryogenesis, is expressed in the duct cells of IFNg mice. This striking observation suggests an important role for PDX-1 in the marked regeneration observed in IFNg mice, paralleling its critical function during ontogeny. Also demonstrated was elevated expression of the homeobox-containing protein Msx-2 in the pancreata of fetal mice as well as in adult IFNg mice, identifying this molecule as a novel marker associated with pancreatic development and regeneration as well. The identification of PDX-1 and Msx in the ducts of the IFNg transgenic pancreas but not in the ducts of the non-transgenic pancreas suggests that these molecules are associated with endocrine precursor cells in the ducts of the IFNg transgenic mouse.

Animals↗
PubMed1998

IL-10 impacts autoimmune diabetes via a CD8+ T cell pathway circumventing the requirement for CD4+ T and B lymphocytes.

IL-10 is essential for an early phase of diabetes in nonobese diabetic (NOD) mice, but later becomes protective against its development. The mechanism by which IL-10 mediates the pathway to diabetes in these mice is unknown. Herein, we dissected the cellular and costimulation requirements for diabetes in transgenic (tg) NOD mice that expressed IL-10 in their pancreatic islets (IL-10-NOD mice). We found that IL-10 alone did not cause diabetes because the offspring (IL-10-NOD-scid mice) from back-crosses of IL-10-NOD mice with NOD-scid mice had no diabetes. Moreover, these IL-10-NOD-scid mice were free of lymphocytic infiltration. Treatment of IL-10-NOD mice with depleting anti-CD4 mAb or control mAb had no effect on diabetes. Surprisingly, depletion of CD8+ T cells by treatment with the corresponding mAb inhibited diabetes without attenuating insulitis, demonstrating a critical role for CD8+ T cells in the disease process. Interestingly, B cell-deficient IL-10-NOD mice readily developed diabetes with kinetics and incidence similar to those observed in wild-type mice, demonstrating that B lymphocytes as APCs were not required in the disease process. Administration of anti-CD40 ligand (CD40L) mAb did not prevent disease, indicating that CD40/CD40L costimulation is not required for diabetes in IL-10-NOD mice. Immunization of IL-10-NOD mice with CFA or heat-shock protein 65, known to block diabetes in NOD mice, had no effect on their diabetes. We demonstrate that IL-10 contributes early to the pathology of diabetes via a CD8+ T cell pathway, eliminating the requirement for B lymphocytes and CD40-CD40L costimulation. Our findings provide a mechanism for the participation of IL-10 in the early development of diabetes.

Animals↗
PubMed1997

How we did it: the development of a specialist registrar training programme by the Mersey Accident and Emergency Trainees' Association.

Over the last three years the accident and emergency trainees in Merseyside have developed a self directed training programme which now consists of twice monthly meetings. This has been achieved through a process of evolution, shaped by the core curriculum, and supervised by the region's consultants with the support of the postgraduate dean. The meetings have proved both popular and valuable. The development and format of the scheme is presented in the hope of stimulating others to work together to improve the training of specialist registrars.

Clinical Competence↗
PubMed1988

Mothers' and fathers' recognition of their newborns' photographs during the postpartum period.

In the present study, we have compared the ability of mothers and fathers to recognize their newborns' photographs during the early postpartum period. We suspected that fathers would prove to be less proficient than mothers, as a result of differences in the quality of their contact with their newborns. Our hypothesis was not confirmed. Rather, mothers and fathers were, for the most part, equally proficient at recognizing their infants. Since focused attention is a requisite for accurate photograph recognition, these data suggest that fathers view their newborns with perspicacity comparable to that of mothers.

Adult↗
PubMed1987

Mothers' recognition of their newborns by olfactory cues.

We report that 90% of women tested in the present study identified their newborns by olfactory cues after only 10 min-1 hr exposure to their infants. All of the women tested recognized their babies' odor after exposure periods greater than 1 hr. The robust results are due in part to the implementation of an initial screening phase in which individuals with obvious olfactory deficits were excluded from the sample. These results suggest that odor cues from newborns are even more salient to their mothers than have been thought heretofore.

Cues↗
PubMed1977

Treatment of ankylosing spondylitis with flurbiprofen and indomethacin.

In a parallel, double-blind and randomized trial of 6-weeks' duration, flurbiprofen (150 mg to 200 mg daily) was compared with indomethacin (75 mg to 100 mg daily) in the management of 26 patients with active ankylosing spondylitis. None of the patients in either group withdrew from the study because of lack of efficacy of the drugs. Both drugs were equally effective in the relief of pain and tenderness of the affected joints. Overall subjective improvement, assessed by the patient and the investigator at the end of the trial, was present in 90% of the patients in the flurbiprofen group and in 75% of those in the indomethacin group. The mean values of all the spinal motion tests improved in the flurbiprofen group but not in the indomethacin group. Statistically significant improvement in the Schober test was achieved in the flurbiprofen group and in chest expansion in the indomethacin group. Characteristic untoward effects related to the central nervous system and gastro-intestinal tract were present in a few patients in both groups.

Clinical Trials as Topic↗
PubMed1977

Molecular forms of human chorionic gonadotropin in serum, urine, and placental extracts.

The molecular forms of human chorionic gonadotropin (hCG) were assessed in serum, urine, and placental extracts by gel filtration chromatography using radioimmunoassays for hCG, hCGalpha, and hCGbeta and a radioreceptor assay for hCG. The predominant form in all three biologic specimens was native-sized hCG. An excess of free alpha-subunit was also found in all three specimens. A small molecular weight fragment, reactive in the hCGbeta assay, was noted in urine and placental extracts. A large molecular form, reactive in all three radioimmunoassays and in the radioreceptor assay, was found in placental extracts. This large molecular species could not be dissociated by conditions that totally dissociate hCG.

Adult↗
PubMedDate not supplied

Reiter's disease after Salmonella typhimurium enteritis.

We describe a case of Reiter's disease in an HLA-B27 positive black woman after infection with Salmonella typhimurium. Although reactive arthropathy following Salmonella infections is not unusual, Reiter's disease is rare. This may be the second such case in the English literature, and the first reported in North America.

Adult↗