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Biomedical subjects

J Moore

Publications and source records attributed to J Moore.

At least 271 records · Page 15Linked to original sources

Antenatal sonographic diagnosis of thanatophoric dysplasia: a report of three cases and a review of the literature with special emphasis on the differential diagnosis.

A series of three cases is reported in which the diagnosis of thanatophoric dysplasia was reached at routine mid-trimester scanning in a District General Hospital. All three patients underwent termination of pregnancy with the diagnosis of thanatophoric dysplasia confirmed by postmortem radiographic and histological examinations. A review of the current literature on thanatophoric dysplasia is given, with special emphasis on the differentiation of the main types of thanatophoric dysplasia from other skeletal abnormalities.

Abortion, Induced↗

Oxybenzone oxidation following solar irradiation of skin: photoprotection versus antioxidant inactivation.

We used noninvasive Fourier transform (FT) Raman spectroscopy to follow the fate of the broadly used ultraviolet UVA sun blocker, oxybenzone, after topical application to the skin. Our results showed that oxybenzone is rapidly photo-oxidized, yielding oxybenzone semiquinone, a potent electrophile, which reacts with thiol groups on important anti-oxidant enzymes and substrates, such as thioredoxin reductase and reduced glutathione, respectively. Although oxybenzone is an excellent broad spectrum UVA filter, its rapid oxidation followed by the inactivation of important antioxidant systems indicates that this substance may be rather harmful to the homeostasis of the epidermis. Furthermore, these results demonstrate that FT-Raman spectroscopy is a useful method for studying the transport and metabolism of active ingredients in topical preparations.

Administration, Topical↗

Three dimensional analysis of the retinal vasculature using immunofluorescent staining and confocal laser scanning microscopy.

AIM: To undertake a qualitative and quantitative analysis in three dimensions of the human retinal vasculature. METHOD: Fixed and excised whole retinas were permeabilised and subjected to immunofluorescent staining for blood vessel components followed by confocal laser scanning microscopy. Single projection and stereoimages were constructed using computer software. XZ sections through the retina were constructed and the vasculature analysed using appropriate software. RESULTS: Immunofluorescent staining with no discontinuities was present in vessels of all sizes, the confocal images of the capillary network being free of out of focus blur at all depths. Quantitative analysis of XZ sections confirmed the qualitative impression of sharp delineation of the deep retinal capillary plexus, an absence of laminar arrangement of capillaries within the inner retina, and a truncated cone of capillaries around the foveal avascular zone (FAZ) wherein the superficial capillaries approached the FAZ more closely than those in the deeper retina. CONCLUSION: Immunofluorescent staining of the retina and confocal laser scanning microscopy were shown to be useful in analysing accurate three dimensional reconstructions of the normal retinal vasculature without affecting overall tissue architecture.

Adult↗

Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer.

PURPOSE: Breast cancer frequently overexpresses the product of the HER2 proto-oncogene, a 185-kd growth factor receptor (p185HER2). The recombinant humanized monoclonal antibody (rhuMAb) HER2 has high affinity for p185HER2 and inhibits the growth of breast cancer cells that overexpress HER2. We evaluated the efficacy and toxicity of weekly intravenous administration of rhuMAb HER2 in patients with HER2-overexpressing metastatic breast cancer. PATIENTS AND METHODS: We treated 46 patients with metastatic breast carcinomas that overexpressed HER2. Patients received a loading dose of 250 mg of intravenous rhuMAb HER2, then 10 weekly doses of 100 mg each. Patients with no disease progression at the completion of this treatment period were offered a maintenance phase of 100 mg/wk. RESULTS: Study patients had extensive metastatic disease, and most had received extensive prior anticancer therapy. Adequate pharmacokinetic levels of rhuMAb HER2 were obtained in 90% of the patients. Toxicity was minimal and no antibodies against rhuMAb HER2 were detected in any patients. Objective responses were seen in five of 43 assessable patients, and included one complete remission and four partial remissions (overall response rate, 11.6%; 95% confidence interval, 4.36 to 25.9). Responses were observed in liver, mediastinum, lymph nodes, and chest wall lesions. Minor responses, seen in two patients, and stable disease, which occurred in 14 patients, lasted for a median of 5.1 months. CONCLUSION: rhuMAb HER2 is well tolerated and clinically active in patients with HER2-overexpressing metastatic breast cancers that had received extensive prior therapy. This is evidence that targeting growth factor receptors can cause regression of human cancer and justifies further evaluation of this agent.

Adult↗

Recombinant human growth hormone (GH)-binding protein enhances the growth-promoting activity of human GH in the rat.

To address the role of the GH-binding protein (GHBP) in GH physiology, two forms of recombinant human GHBP (rhGHBP) were given alone or in combination with rhGH to hypophysectomized rats or GH-deficient dwarf rats. Hypophysectomized rats were given daily sc injections of excipient, hGH, rhGHBP, or rhGH plus rhGHBP (produced in Escherichia coli) for 7 days. Injections of rhGH induced dose-related body weight gain and bone growth that were increased by the coadministration of rhGHBP with rhGH; rhGHBP alone had no effect. Serum insulin-like growth factor increased 24 h later when rhGH was given together with rhGHBP (P < 0.01), but not when rhGH was given alone. E. coli-derived rhGHBP also enhanced the bioactivity of coadministered rhGH in the GH-deficient dwarf rat. In contrast, the glycosylated rhGHBP, made in human A293 cells, inhibited the growth-promoting activity of coadministered rhGH. The opposite effects of these two forms of rhGHBP could be explained by clearance studies that showed radiolabeled rhGH bound to A293 cell-derived rhGHBP to be cleared more rapidly from the blood than free rhGH. Natural rabbit GHBP and E. coli-derived rhGHBP both prolonged the presence of rhGH in blood. It is proposed that by slowing the clearance of GH, GHBP increased the bioactivity of GH. In summary, codelivery of rhGHBP and rhGH caused a dose-dependent enhancement of the activity of rhGH in two rat models of GH deficiency. This suggests that endogenous circulating GHBP may increase the activity of blood-borne GH in a similar manner.

Animals↗

Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the U.S. EPA-sponsored workshop.

The hypothesis has been put forward that humans and wildlife species adverse suffered adverse health effects after exposure to endocrine-disrupting chemicals. Reported adverse effects include declines in populations, increases in cancers, and reduced reproductive function. The U.S. Environmental Protection Agency sponsored a workshop in April 1995 to bring together interested parties in an effort to identify research gaps related to this hypothesis and to establish priorities for future research activities. Approximately 90 invited participants were organized into work groups developed around the principal reported health effects-carcinogenesis, reproductive toxicity, neurotoxicity, and immunotoxicity-as well as along the risk assessment paradigm-hazard identification, dose-response assessment, exposure assessment, and risk characterization. Attention focused on both ecological and human health effects. In general, group felt that the hypothesis warranted a concerted research effort to evaluate its validity and that research should focus primarily on effects on development of reproductive capability, on improved exposure assessment, and on the effects of mixtures. This report summarizes the discussions of the work groups and details the recommendations for additional research.

Animals↗

Safety and immunogenicity of Staphylococcus aureus type 5 capsular polysaccharide-Pseudomonas aeruginosa recombinant exoprotein A conjugate vaccine in patients on hemodialysis.

Seventeen volunteers with ESRD on hemodialysis, negative for infection with HIV or hepatitis B and C and not receiving immunosuppressive therapy, were injected two times 6 wk apart with 25 micrograms of Staphylococcus aureus Type 5 capsular polysaccharide-Pseudomonas aeruginosa exoprotein A (rEPA) conjugate. Controls were healthy adults, 18 to 44 yr old, injected previously with the same vaccine. None of the patients had fever or significant elevations in their SGOT or SGPT attributable to the vaccine. Two vaccinees had transient induration > 1 cm in diameter at the injection site. The preimmunization geometric mean (GM) Type 5 antibody levels of the ESRD patients and controls were similar. Type 5 antibody levels of the three major immunoglobulin (lg) classes rose at 2 and 6 wk after immunization (P < 0.001 for lgG, P < 0.005 for lgM, and P = 0.0001 for lgA). Reimmunization at 6 wk did not elicit a booster response. At 6 months, the GM lgG level of the patients was approximately 50% of that of the healthy volunteers and 14 of 17 had a more than fourfold higher antibody level than the preimmune value. The GM lgM level, in contrast, declined to the preimmunization value. Vaccine-induced Type 5 antibodies had opsonophagocytic activity. There was a slight increase of lgG antibodies to the heterologous S. aureus Type 8 polysaccharide (P < 0.01) that was sustained at 6 months. The S. aureus Type 5-rEPA vaccine is safe and immunogenic in ESRD patients, and evaluation of its effectiveness against S. aureus bacteremia in this at-risk group is planned.

ADP Ribose Transferases↗

Blocking, unblocking, and overexpectation in autoshaping with pigeons.

Three experiments used pigeons in an autoshaping procedure and a single-subject design to examine compound stimulus control in classical conditioning. Experiment 1 examined the blocking effect, and Experiment 2 examined the unblocking effect. In both experiments, response-independent food was first delivered intermittently in the presence of one distinctively colored houselight but not another. Then, conventional autoshaping trials were carried out in the presence of each houselight. In Experiment 1, the keylight readily elicited responding in the presence of the houselight that had been negatively correlated with food, but not in the presence of the houselight that had been positively correlated with food. In Experiment 2, the keylight readily elicited responding in the presence of the houselight positively correlated with food, but only when the amount of food used on the autoshaping trials was either greater or less than that previously delivered in the presence of the houselight. Experiment 3 examined the overexpectation effect. Conventional autoshaping trials were first carried out by presenting each of two keylights individually. Then, additional autoshaping trials were carried out by presenting the two keylights as a compound, with either the same amount of food or a greater amount of food per trial. Finally, the keylights were retested by again presenting them individually. The number of responses per trial elicited by the keylights decreased when the amount of food used in compound trials was the same as that used in individual trials. However, the number of responses per trial remained approximately the same when the amount of food used in compound trials was greater than that used in individual trials. Taken together, the results of the three experiments demonstrate (a) the generality of the blocking, unblocking, and overexpectation effects by virtue of their extension to appetitive unconditioned stimuli; (b) the suitability of pigeons as subjects and autoshaping as a procedure for studying classical conditioning; and (c) the appropriateness of single-subject designs.

Journal Article↗