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Biomedical subjects

M Parker

Publications and source records attributed to M Parker.

At least 217 records · Page 12Linked to original sources

Organization and expression of prostatic steroid binding protein genes.

The function of regulatory regions of DNA, which flank the genes for prostatic steroid binding protein, is being analysed by introducing the cloned genes into heterologous cells. Two non-allelic genes for the C3 polypeptide, C3(1) and C3(2) have been transfected into androgen-responsive S115 cells using SV2-gpt vectors. The genes have been introduced either intact or as so-called fusion genes consisting of putative C3 promoters plus human beta-interferon cDNA. Both genes for C3 were accurately transcribed and their expression was stimulated 5-10-fold with 10(-8) M testosterone. Thus we should be able to define at least one region of DNA which confers androgen sensitivity to the genes. Although both genes were expressed similarly in S115 cells only C3(1) is responsible for C3 in vivo and C3(2) is transcribed poorly, if at all. The most likely explanation for the difference is that in vivo the C3(2) gene remains hypermethylated whereas the DNA which was introduced into S115 cells was unmethylated. This result supports the notion that the state of DNA methylation is important for controlling the transcription of genes.

Androgen-Binding Protein↗

Organization and expression of genes encoding prostatic steroid binding protein.

We have cloned the genes for prostatic steroid binding protein to study the mechanism whereby their expression is regulated by testosterone. The genes for the C1 and C2 polypeptides are probably unique whereas there are two genes C3(1) and C3(2) for the C3 polypeptide of which only the former is transcribed in vivo. The state of DNA methylation associated with the two genes for C3 also differ, insofar as C3(1) is demethylated in ventral prostate from 14-28 days of age, whereas the C3(2) gene remains hypermethylated. The organization of all four genes is similar and appreciable DNA sequence homologies suggest that they may have arisen from a single ancestral gene. To study C3 expression and its hormonal regulation we have introduced the cloned genes into mouse S115 cells, an androgen-responsive cell line. Both genes were accurately transcribed and their expression was stimulated up to fivefold by 10(-8) M testosterone in approximately one third of the clones tested. To delineate the site of action of the hormone we have constructed chimeric genes consisting of putative C3 promoters and regulatory sequences together with a marker gene, interferon. This chimeric gene resulted in interferon production but its expression was stimulated by less than twofold in all clones tested. Therefore, these results indicate that, in mouse cells, testosterone does not interact directly with the rat C3 promoter but, in certain clones, may act post-transcriptionally.

Androgen-Binding Protein↗

Pediatric cardiopulmonary resuscitation. A review of 130 cases.

Cardiopulmonary resuscitation (CPR) records of 130 pediatric patients with cardiac arrest were reviewed. Ninety-six resuscitations were performed on patients hospitalized on the Medical and Surgical units of the Children's Hospital of Philadelphia (HP) and 34 on Emergency Department patients (EDPs). In HP, initial survival was 90%. In 27% of HPs, airway and breathing techniques alone were life saving. A mean of 2.45 drugs per patient were used for HP. In EDP, initial survival was 56%. There had been advanced CPR during the prehospital transport phase for the EDPs. All but two EDPs required drug management. The mean was 4.25 drugs per patient. Lidocaine and direct current defibrillation were used only rarely. Glucose was used frequently (33%) and should be considered in the list of essential resuscitation drugs. The necessity for resuscitation was most commonly associated with pulmonary diseases. These findings reflect differences between pediatric CPR and adult CPR, and suggest limitations in applying adult standards to infants and children. It is suggested that the medical community develop separate pediatric CPR courses as independent modules for those who assume responsibility for resuscitating children.

Adolescent↗

Control of a rubella outbreak in a dental school population.

This study traces the development of a rubella outbreak; 16 clinical and one sub-clinical case were detected. Overall, the incidence of infection was higher for males than females. Susceptibility rates determined by the absence of primarily IgG antibodies indicated that class association, social contact, and preexisting susceptibility patterns influenced the differences in attack rates seen among the classes. In spite of a higher susceptibility caused in part by the number of foreign students enrolled, no infections occurred in the graduate student population. Concern for the spread of rubella to susceptible students and personnel within the dental school, among adjunct dental assistant and hygiene programs and others at the adjacent medical school and hospitals, led to a comprehensive immunization policy. All dental and medical personnel, regardless of clinical contact, must present proof of immunity or be immunized.

Disease Outbreaks↗

Developmental changes in DNA methylation around prostatic steroid-binding protein genes.

The state of DNA methylation around prostatic steroid-binding protein genes has been investigated at CCGG sites by using the restriction enzymes MspI and HpaII. In the ventral prostate, these sites change from being completely methylated around the C1, C2, and one of two C3 genes in 10-day-old animals to being unmethylated in 28-day-old animals. The second C3 gene is always methylated and probably transcriptionally inactive, and all four genes are hypermethylated in other tissues. Hormone withdrawal from mature animals results in methylation of approximately 50% of CCGG sites in the ventral prostate which correlates with an increase in the number of stromal cells relative to epithelial cells. This suggests that the state of DNA methylation in epithelial cells, where prostatic steroid-binding protein is expressed, is unchanged. Thus, the inverse correlation between gene expression and DNA methylation is valid during development but probably not during subsequent hormone withdrawal.

Aging↗

Intravenous nitroglycerin for the treatment of angina at rest unresponsive to standard nitrate therapy.

Thirty-five patients who had angina at rest that was unresponsive to standard therapy comprised of oral or topical nitrates and beta-blocking drugs were treated with a continuous infusion of intravenous nitroglycerin (IVNTG). The infusion was started at 10 micrograms/min and increased by 10 micrograms/min increments every 5 minutes until an infusion rate of 50 micrograms/min was reached. After each episode of rest angina, the infusion was increased by 50 micrograms/min in the same stepwise manner. Data from a 24-hour baseline control period were compared with those from a 24-hour IVNTG endpoint period at which time the highest IVNTG infusion rate was administered. The average IVNTG infusion rate was 140 +/- 15 micrograms/min. With IVNTG therapy, the number of episodes of angina at rest decreased from 3.5 +/- 0.4 to 0.3 +/- 0.1, sublingual nitroglycerin use decreased from 1.9 +/- 0.3 to 0.4 +/- 0.1 mg/day, and morphine sulfate administration decreased from 5.5 +/- 1.3 to 0.4 +/- 0.2 mg/day (all p less than 0.001). When each patient's response on the endpoint day was analyzed, 25 were defined as complete (no rest angina), 8 as partial (greater than 50% decrease in the number of episodes/day from control values), and 2 as nonresponders. No significant drug-induced adverse effects occurred. IVNTG appears to be effective therapy for angina at rest refractory to standard oral and topical medications.

Adult↗

Atrial fibrillation and flutter. Immediate control and conversion with intravenously administered verapamil.

The safety and efficacy of the intravenous (IV) calcium channel blocker, verapamil, in controlling the ventricular response or converting to sinus rhythm patients with atrial flutter or atrial fibrillation were assessed. Seventeen patients (nine with atrial flutter and eight with atrial fibrillation) with these arrhythmias that were difficult to control pharmacologically were chosen for the study. All patients at the time of study were receiving digoxin. Either verapamil or placebo was chosen randomly and a bolus of 0.075 mg/kg (up to 5 mg) was administered. Twelve patients had a marked reduction in their ventricular response after IV administration of verapamil (seven with atrial flutter and five with atrial fibrillation). None of these 12 patients converted (nonconverters). The average reduction in heart rate was from 120 +/- 6 beats per minute to a minimum of 83 +/- 13 beats per minute within 20 minutes after drug administration. Verapamil was found to convert five patients with atrial arrhythmias to sinus rhythm (two with atrial flutter and three with atrial fibrillation) (converters). In addition, three patients with atrial arrhythmias of less than one month who did not convert with parenteral drug therapy converted within 24 hours while receiving the oral drug. Converters had their supraventricular arrhythmias of significantly shorter duration (median, three hours v 30 days) and tended to have smaller left atrial size (3.8 +/- 0.7 cm v 4.3 +/- 1.3 cm) compared with the nonconverters. We conclude that verapamil is safe and effective when administered IV to patients with atrial flutter and fibrillation for control of ventricular response. In short duration atrial arrhythmias, conversion to sinus rhythm is likely once the ventricular response is controlled.

Adult↗

A simple method to improve the energy value of bank human milk.

Drip milk can be collected in large amounts, hence its potential value for human milk banks. This advantage is however offset by its low energy value. For those milk banks which depend mostly on drip milk, the energy value of its donor milk can be improved to a more acceptable level, and total volumes of donations increased, by encouraging mothers to combine collections of both drip and expressed milk.

Female↗

Pneumocystis carinii identified by gram stain of lung imprints.

The diagnosis of Pneumocystis carinii pneumonia conventionally depends on the time-consuming demonstration of the organisms in pulmonary secretions or lung tissue using toluidine blue 0, methenamine silver, or Gram Weigert stains that require special reagents. In 27 recent episodes of moderate to heavy pneumocystis infections, the cyst form and internal sporozoites of P. carinii could be readily identified on lung imprints using the conventional Gram stain. The Gram stain is unlikely to replace special stains for the diagnosis of pneumocystosis, but it does provide a rapid method to recognize moderate to heavy infections.

Female↗

Cancer in Solomon Islands 1970-82.

An analysis of the pathology reports of cancer at the Central Hospital, Honiara, Solomon Islands from 1970 to 1982 revealed that skin cancer, lymphohaemopoietic malignancy, cancer of the digestive organs and oral cancer were the most common cancers in males, and that cancer of the genito-urinary organs, skin cancer, breast cancer and lymphohaemopoietic malignancy were the most common cancers in females. Leukaemia and lymphoma were the most common cancers diagnosed in children. Although this is a selected series, there are definite similarities with cancer data reported from Papua New Guinea, and significant differences from patterns of cancer reported from Australia. Cancer of the mouth and liver appear to be more common in Solomon Islanders, and cancer of the large bowel and lung less common compared with Australians. These differences probably relate to the effect of different environmental agents. The present prospects for prevention and control of cancer in Solomon Islands is discussed.

Adult↗

Prostatic steroid binding protein: organisation of C1 and C2 genes.

Prostatic steroid binding protein, whose expression is stimulated by androgens, consists of two subunits: one containing the polypeptides C1 and C3 and the other containing C2 and C3. We have characterised genomic clones containing the C1 and C2 genes by restriction enzyme analysis and DNA sequencing. Both genes are 3.2 Kb, have similar exon/intron arrangements and share considerable DNA sequence homologies in their coding regions, intervening sequences and 5' upstream DNA sequence which suggests that they have probably arisen from the duplication of an ancestral gene. The 5' termini of C1 and C2 mRNA have been mapped; the sequence TATAAA appears 30 nucleotides upstream but a CAAT-like sequence at -60 - -80 is absent. Finally, homologous human genes have not been detected.

Androgen-Binding Protein↗