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Biomedical subjects

J Blount

Publications and source records attributed to J Blount.

15 recordsLinked to original sources

Activation tagging identifies a conserved MYB regulator of phenylpropanoid biosynthesis.

Plants produce a wide array of natural products, many of which are likely to be useful bioactive structures. Unfortunately, these complex natural products usually occur at very low abundance and with restricted tissue distribution, thereby hindering their evaluation. Here, we report a novel approach for enhancing the accumulation of natural products based on activation tagging by Agrobacterium-mediated transformation with a T-DNA that carries cauliflower mosaic virus 35S enhancer sequences at its right border. Among approximately 5000 Arabidopsis activation-tagged lines, we found a plant that exhibited intense purple pigmentation in many vegetative organs throughout development. This upregulation of pigmentation reflected a dominant mutation that resulted in massive activation of phenylpropanoid biosynthetic genes and enhanced accumulation of lignin, hydroxycinnamic acid esters, and flavonoids, including various anthocyanins that were responsible for the purple color. These phenotypes, caused by insertion of the viral enhancer sequences adjacent to an MYB transcription factor gene, indicate that activation tagging can overcome the stringent genetic controls regulating the accumulation of specific natural products during plant development. Our findings suggest a functional genomics approach to the biotechnological evaluation of phytochemical biodiversity through the generation of massively enriched tissue sources for drug screening and for isolating underlying regulatory and biosynthetic genes.

Amino Acid Sequence↗

Sexually transmitted diseases and communications with general practitioners.

OBJECTIVES: To devise a method of communicating with the general practitioners (GPs), overcoming the constraints imposed by patient confidentiality and the low levels of staffing in genitourinary medicine (GUM) clinics. To assess the GPs' responses to this method of communication. SETTING: GUM clinics at two centres in Kent-Maidstone and Tunbridge Wells. METHODS: Patients were recruited if they attended the clinic of their own accord without a letter of referral from their GPs; a definitive or provisional diagnosis was made and the patient was managed in the clinic; the patient's GP had received a conventional reply from the GUM clinic for other patients referred in the past. Separate GP letters were developed for male and female patients. These handwritten study letters were read by the patients who took the responsibility to deliver them to their GPs. This was followed by a questionnaire to the GPs. RESULTS: 75 patients were eligible. Seven patients refused to participate. All questionnaires were returned by the GPs for the 68 participating patients (100%). Seven GPs failed to receive the study letter. For these unreferred patients, this was an improvement in communication level from 0% to 80%. 79% (95% confidence interval: 67%-87%) preferred the study letter, 97% (89%-99%) would like to receive a similar letter for future patients. All GPs thought that the study letter was at least as good as the standard letter 52% (40%-64%) thought it was better. For 82% (70%-90%) it was the preferred format for future communication. CONCLUSION: The study has shown a way of establishing communication with GPs for patients who do not object to this. The results also suggest that in the study districts neither the GPs nor the majority of study patients had any objection to the sharing of information between the GUM clinics and GPs.

Ambulatory Care↗

Craniocephalic disproportion with increased intracranial pressure and brain herniation: a new clinical syndrome in anemic patients: report of two cases.

OBJECTIVE AND IMPORTANCE: We describe a new clinical syndrome in two patients with chronic anemia. The major manifestation of the syndrome is herniation of the brain resulting in death caused by longstanding craniocephalic disproportion. The disproportion was caused by extreme thickening of the cranium because of erythroid hyperplasia. CLINICAL PRESENTATION: Two patients with known chronic anemia presented with chronic increase in intracranial pressure with acute deterioration resulting in brain herniation. INTERVENTION: Despite maximum medical therapy, both patients died as a result of uncontrollable increase in intracranial pressure. CONCLUSION: Patients with chronic anemia presenting with progressive headaches should be monitored for this newly described clinical phenomenon.

Adult↗

Validation of PTSD measures for older combat veterans.

This study evaluated three nosologically similar older groups (Older PTSD, POW, and Older Psychiatric) and a group of Younger PTSD veterans from Vietnam. Group membership was derived from index admission diagnoses and clinical validation of status. Groups were compared on the MMPI, PTSD measures, background variables, health measures and an outcome measure. Results showed that the Older PTSD group is closer to the Younger PTSD group than to the other groups on the MMPI and PTSD measures and also that members of this group remain in the hospital longer than do members of the other older groups. Parameters of effective test classification showed the PTSD measures to be helpful in correct identification of this disorder for the older groups.

Age Factors↗

Comprehensive system Rorschach data on Vietnam combat veterans.

To better understand and, therefore, treat Vietnam combat veterans with a diagnosis of posttraumatic stress disorder (PTSD), the Rorschach was administered to 50 patients so diagnosed. The most important findings were that, on average: (a) These patients have a low level of stress tolerance and are, therefore, likely to respond impulsively to stressful situations; (b) this low stress tolerance appears to be a long-term adjustment problem; and (c) their perception of reality is unconventional and often distorted. A primary therapeutic indication from these data is that the use of structure would be important for successful therapy. Other findings and therapeutic recommendations are also discussed.

Adult↗

Acylmorphinans. A novel class of potent analgesic agents.

A series of novel 2- and 3-acylmorphinans (8-14) was synthesized in our search for a potent analgesic agent with low addiction potential. The compounds were evaluated for antinociceptive potency and receptor binding affinity. Among these compounds, the levorotatory 3-acetyl-N-(cyclopropylmethyl)morphinan (12) was found to be an orally active analgesic, comparable in potency to morphine (1), yet only weakly able to substitute for morphine (1) in morphine-dependent rats.

Analgesia↗

2-benzazepines. 6. Synthesis and pharmacological properties of the metabolites of 9-chloro-7-(2-chlorophenyl)-5H-pyrimido[5,4-d] [2]benzazepine.

The 2-benzazepine 9-chloro-7-(2-chlorophenyl)-5H-pyrimido[5,4-d] [2]benzazepine (1) has been selected for development as an anxiolytic agent. In support of this program, we have confirmed by chemical synthesis the structures of three in vitro (rat liver homogenate) metabolites of 1 and confirmed the structure of the major in vivo (dog and man) metabolite of 1, compound 2. Two of the metabolites, arising from hydroxylation of the pyrimidobenzazepine ring at the 5-position (2) and N-oxide formation at the 3-position of the pyrimidobenzazepine ring (3), were found to be as active as 1 in a series of pharmacological tests. The third metabolite, formed by hydroxylation of the 7-phenyl group in the 4-position (4), was found to be inactive in the same pharmacological screens.

Animals↗

Arteriovenous extracorporeal carbon dioxide removal: a mathematical model and experimental evaluation.

To explore the feasibility and operating limits of arteriovenous extracorporeal CO2 removal (AVCO2R) for support of acute respiratory failure, the authors developed a mathematical model to simulate (AVCO2R), evaluate the effects of several parameters used in its application, and predict the feasibility and necessary conditions for total CO2 removal. The mathematical model incorporated compartments representing blood, pulmonary alveoli, pulmonary capillaries, peripheral tissues and capillaries, and an extracorporeal gas exchange device. The model was validated against an animal model of extracorporeal CO2 removal. This model consisted of anesthetized and mechanically ventilated piglets. An extracorporeal CO2 removal device was placed by cannulation of a femoral artery and vein. Dynamic and steady state measurements of CO2 transfer were made and compared with simulations using the mathematical model. There was good agreement between experimental and simulated data, validating the mathematical model under a variety of conditions. The mathematical model was used to determine operating parameters for total CO2 removal. Relationships between extracorporeal blood flow, device diffusing capacity, and device gas sweep flow were established for CO2 removal at various levels of CO2 production. These simulations indicate that it is possible to achieve total CO2 removal using an extracorporeal shunt fraction of 10%-15% of cardiac output, a device diffusing capacity of 0.5 ml x min(-1) x torr(-1) (kg body weight)(-1), and a gas:blood flow of 5 or greater.

Animals↗

Pelvic inflammatory disease in the United States. Incidence and trends in private practice.

The National Ambulatory Care Survey, conducted by the National Center for Health Statistics (Rockville, Md.), provides national estimates for conditions diagnosed by office-based private practitioners in the United States. The Venereal Disease Control Division of the Centers for Disease Control (Atlanta, Ga.) obtained data from the National Ambulatory Care Survey for the years 1973-1976 and analyzed the epidemiology of pelvic inflammatory disease in women who sought care from private physicians. More that 7.5 million office visits for pelvic inflammatory disease were made over the four-year period (average, 1.89 million visits pe year). All races other than white bear a disproportionate burden of pelvic inflammatory disease. Since the advent of the National Gonorrhea Screening Program in 1972, the number of visits to private physicians for pelvic inflammatory disease has apparently declined.

Adolescent↗