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Biomedical subjects

M Mellon

Publications and source records attributed to M Mellon.

12 recordsLinked to original sources
PubMed1991

Identification of a zinc finger protein that inhibits IL-2 gene expression.

Transient activation of the interleukin-2 (IL-2) gene after antigen recognition by T lymphocytes is crucial for subsequent T cell proliferation and differentiation. Several IL-2 gene regulatory elements and binding factors necessary for activation of the IL-2 gene have been defined. However, little is known about negative regulation of IL-2 expression, which is likely to be important in the rapid shut-off of IL-2 transcription. A nucleotide sequence element (NRE-A) that negatively regulates IL-2 expression has been identified within the IL-2 gene. T cell nuclear extracts contained an NRE-A binding activity. A complementary DNA was isolated that encodes a zinc finger-containing protein that suppressed IL-2 gene expression. The observation of negative regulation of the immunoglobulin heavy chain gene enhancer by an element similar to NRE-A suggests that related proteins may regulate multiple immune response genes.

Amino Acid Sequence↗
PubMed1990

DNA sequencing in HydroLink matrices: extension of reading ability to greater than 600 nucleotides.

All the systems for optimizing DNA sequencing published so far have introduced modifications regarding: (i) linearization of band migration via ionic strength gradients or wedge-shaped gels; (ii) automatization of band reading via introduction of fluorescent probes; (iii) direct blotting analysis; (iv) pulsed electric fields and (v) discontinuous buffer systems. In all these systems, DNA sequence reading with an accuracy of ca. 98% rarely exceeds a length of 350 bases. We have chosen, in order to increase the reading ability of a single gel, to manipulate the characteristics of the gel matrix. The Seq-HydroLink gel formation here reported allows optimal reading, from a single gel run, of at least 600 bases. In order to guarantee this reading ability in a single run, the upper and lower ends of the ladder are time-resolved, i.e. the same sample is applied to the gel matrix at three different time intervals. The present system represents an increase of at least 30% in reading ability as compared with any type of polyacrylamide gel formulation so far reported.

Bacteriophages↗
PubMed1988

A multicenter evaluation of the clinical benefits of cromolyn sodium aerosol by metered-dose inhaler in the treatment of asthma.

The efficacy and safety of cromolyn sodium by metered-dose inhaler (MDI) (1 mg per actuation) was evaluated with a double-blind, placebo-controlled, parallel-study design. Subjects with asthma, aged 8 to 58 years, whose asthma was well controlled taking cromolyn sodium capsules by Spinhaler turboinhaler, plus beta 2-agonists, entered the study after being maintained with cromolyn sodium capsules for a minimum of 4 weeks. The investigation began with a 2-week control interval with cromolyn sodium capsules followed by a 4-week single-blind period with placebo capsules. Subjects whose asthma significantly worsened while they were receiving placebo therapy were then randomized to a 10-week double-blind phase in which they received either active cromolyn sodium or placebo by MDI. Efficacy variables included diary data, physician evaluation, and spirometry. Comparisons were made between baseline period scores and each assessment variable over time. Of 155 subjects entered, 93 qualified for the double-blind, randomized phase. Eighty-three subjects completed the study and were analyzed. At baseline there existed no significant differences between the active-treatment and placebo-treatment groups. Significant differences (p less than 0.05) in favor of the cromolyn sodium-treatment group, however, were noted at all time points for daily diary symptoms (cough, breathlessness, and overall asthma severity), physician's assessments at each clinic visit, physician's and patient's overall final assessments, FEV1 at each clinic visit, and FVC and peak expiratory flow rate at the final visit. Concomitant bronchodilator medication use was less in the cromolyn sodium-treatment group. Cromolyn sodium by MDI is highly effective for (1) controlling asthmatic symptoms, (2) improving lung functions, and (3) decreasing the need for concomitant bronchodilators.

Administration, Inhalation↗
PubMed1987

The effectiveness of nalbuphine and hydroxyzine for the emergency treatment of severe headache.

The present treatment for acute attacks of headache is empiric. Intramuscular nalbuphine (Nubain) and hydroxyzine (Vistaril) were assessed for pain relief in a prospective, double-blind clinical trial. Ninety-four patients were assigned randomly to treatment groups receiving nalbuphine 10 mg, nalbuphine 10 mg plus hydroxyzine 50 mg, hydroxyzine 50 mg, or placebo. The treatment groups were found to be adequately homogenous with regard to age, sex, type and duration of headaches, and history of prior narcotic use. All data were analyzed by one-way analysis of variance. Patients who had headaches diagnosed as other than classic migraine had significantly greater pain relief with nalbuphine compared to placebo (P less than .01). The combination of nalbuphine and hydroxyzine was not significantly more effective than other treatment groups. In 20 patients with classic migraine, none of the treatment regimens significantly outperformed placebo. There were no clinically significant adverse effects attributed to the study drugs. These findings are similar to others that showed a lack of efficacy of kappa receptor agonists in classic migraineurs. Nalbuphine appears to be clinically useful in other types of severe headache. This study does not support the routine addition of hydroxyzine for presumed synergistic effect.

Adult↗
PubMed1987

Long-term studies in prevention of food allergy: patterns of IgG anti-cow's milk antibody responses.

Over the past 7 years we have enrolled several hundred families in a study of the prophylaxis of atopic allergy. Initially, control and study patients were at different institutions, but more recently a true double-blind random assignment to control or study group has been instituted. Nevertheless, all of the infants from these highly atopic families can be utilized to obtain the data reported; that is, the rate of change of IgE levels, the appearance of food sensitization (food-specific IgE), the signs and symptoms of atopic allergy diseases and the changes in cow's milk-specific IgG antibody during the first 2 years of life. Some aspects of the first three of these parameters have been presented in the eight references to this paper, but only preliminary data on the use of IgG anti-cow's milk antibody as a measure of compliance has been available. In this paper an analysis is presented of the various patterns of IgG antibody levels in the first 60 infants of the over 200 who have been studied to date. Both the age of onset and the subsequent changes in the foregoing immunologic measurements provide fundamental data with which to measure the success rate of any prophylactic or therapeutic regimen and may improve our capacity to predict the future course of infants and children with a strong familial tendency to allergy.

Animals↗
PubMed1986

Effectiveness of dietary manipulation in the prevention of food allergy in infants.

The desire to alter the natural incidence of atopic illness has piqued physicians' imaginations for decades. Specifically, the phenotypic expression of IgE-mediated disorders, which appears regulated by multiple genetic factors and modulated by environmental experiences (allergen exposure, infection, and smoking), has been a target for preventive medicine since the 1920s when dietary intervention was espoused in infancy. To be successful, such intervention must overcome many patient factors that in concert markedly increase the risk for development of atopic disease (Table XII). During the past 60 years, much controversy has emerged from multiple clinical studies designed to evaluate the effect of dietary and other environmental exclusions on the subsequent manifestation of atopy. One may conservatively conclude, from critical evaluation of these conflicting studies, that sole breast feeding for about 6 months combined with delayed introduction of solid foods for at least 6 months may reduce atopic dermatitis and food allergy in early infancy. A randomized, prospective study of allergy prophylaxis during infancy is mandatory to determine definitely the benefits and feasibility of such a regimen and its long-term effects on the development of atopy. From our recent findings, which demonstrate the development of atopy in infants entered in a strict prophylactic protocol, it becomes apparent that monumental obstacles confront preventive efforts to overcome the strength of the allergic constitution. In the very near future, results from our prospective study of prenatally randomized allergy prophylaxis should be available for critical scrutiny of the effectiveness and feasibility of allergy prevention during infancy.

Breast Feeding↗
PubMed1976

Cyclic nucleotides, thioldisulfide status of proteins, and cellular control processes.

It is shown that cyclic nucleotides can have a variety of effects on cell division, cell shape, cell adhesion, and cell movement, depending on the cells selected and the conditions under which they are used. For example, while CHO cells elongate under the influence of exogenous dibutyryl CAMP, Y-1 adrenal tumor cells round up and polyoma-transformed 3T3 cells show no change in shape. The totality of experience with cyclic nucleotides suggests that where they have been used by cells as control elements involving the four processes listed above, they are superimposed on basic cellular processes that progress in their absence--that is, they must be acting indirectly. In attempting to understand the inhibitory action of methyl xanthines on egg development, we were forced to abandon the idea that they acted through cyclic nucleotides. We found that methyl xanthines inhibited the activation of glutathione reductase and that glutathione oxidizing agents act as mitotic inhibitors. Further, we found that tubulin polymerizability, NAD-kinase activity, and a mitotic apparatus associated Ca+2-ATP-ase were all inhibited by oxidation of some of their sulfhydryls and were activated by reduction of the resulting disulfides. These results are discussed in terms of reported cycles and activations of glutathione reductase (GR) in cells and reports that mixed disulfides of glutathione and proteins can act as substrates for GR. Using the fact that a CAMP-dependent protein kinase has been reported to be activated by glutathione, we have suggested potential sites where sulfhydryl control processes and cyclic nucleotide control processes and cyclic nucleotide control processes may interact in certain restricted cases.

Adenosine Triphosphatases↗