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Biomedical subjects

K A Parker

Publications and source records attributed to K A Parker.

At least 19 recordsLinked to original sources

Electrocyclic ring closure of the enols of vinyl quinones. A 2H-chromene synthesis.

Thermolysis of enolizable vinyl quinones in polar, aprotic media provides 2H-chromenes. Experimental evidence supports a two-step mechanism in which enolization is followed by a thermal 6pi-electrocyclic reaction of an intermediate quinone methide. Application of this method led to the total synthesis of the reputed structure of an Ageratum juvenile hormone. When enolizable vinyl quinones are the products of Stille coupling, the chromene annulation product is obtained directly. [reaction: see text]

Benzopyrans↗

Effect of the universal base 3-nitropyrrole on the selectivity of neighboring natural bases.

[structure: see text] The effect of the universal base 3-nitropyrrole on the pairing selectivity of neighboring nucleosides has been determined for every combination of complementary and neighboring nucleosides. In a subset of cases the discriminatory ability of the neighboring nucleoside for its Watson-Crick complement is compromised. The results have implications for the hybridization of oligonucleotides that contain 3-nitropyrrole and suggest caution in the use of oligonucleotides that contain other universal bases.

Base Pair Mismatch↗

Providing low-cost sexually transmitted diseases services in two semi-urban health centers in Central African Republic (CAR): characteristics of patients and patterns of health care-seeking behavior.

BACKGROUND: While treatment of symptomatic sexually transmitted diseases (STDs) has been shown to reduce the incidence of HIV infection, there are few published reports describing the delivery of high quality STD care in Africa. GOAL: To test the feasibility of providing comprehensive, affordable STD services through the existing primary care infrastructure. DESIGN: STD treatment services using a syndromic' approach were established in two semi-urban hospital outpatient departments (OPD) in Central African Republic (CAR). A dedicated paramedical provider took a clinical history, performed an examination, explained the diagnosis and the importance of referring partners, dispensed drugs, and offered partner referral vouchers. A fee-for-service system was used to resupply drugs initially purchased with project funds. RESULTS: Of 9,552 visits by index patients and partners over a 28-month period starting in October 1993, 60% were made by women; of these women, 90% were symptomatic, 77% had "vaginal discharge," 70% "lower abdominal pain," and 7% "genital ulcer." Among men, 64 % were symptomatic, 38 % had "urethral discharge," and 14% "genital ulcer." Half of all symptomatic patients presented within 1 week of the onset of symptoms; 44% of men compared to 18% of women had sought care elsewhere before the clinic visit. The average cost per STD treated with recommended drugs was $3.90. Etiologic data from subpopulations in both sites suggest that a high proportion of patients was infected with an STD. CONCLUSIONS: Comprehensive yet affordable care for STDs in persons (and their partners) who recognize symptoms is feasible and should be widely implemented in primary care systems to prevent the spread and complications of STDs and HIV in Africa.

Adolescent↗

Patient-led partner referral enhances sexually transmitted disease service delivery in two towns in the Central African Republic.

In Bambari and Bria, 2 towns in the Central African Republic (CAR), we analysed a patient-led partner referral programme within enhanced sexually transmitted disease (STD) services. New (index) patients received syndromic management, counselling about notifying and treating contacts, and vouchers for distribution. From October 1993 to February 1996, 5232 and 4320 patient visits, of which 1814 (35%) and 4320 (30%) were contact referral visits, were logged in Bambari and Bria, respectively. Vouchers were distributed for at least 90% of contacts. Index and contact patients had similar age and sex distributions. In both towns, having a spouse (Bambari: odds ratio [OR] 1.5, 95% confidence interval [CI] 1.4-1.7; Bria: OR 1.9, 95% CI 1.5-2.3) was a factor associated with successful referral of a partner. Successful referral was accomplished by both male and female patients. Appropriate counselling techniques and vouchers facilitated partner referral. Further research on how to reach casual partners would enhance STD control efforts using patient-led partner referral.

Adolescent↗

Diet and athletic performance.

Inadequate diet inhibits optimal performance in otherwise well-trained athletes. Controversy exists regarding specific dietary requirements, particularly in the areas of protein and vitamin/mineral supplementation. This article reviews energy substrate utilization, provides an overview of nutrient requirements during exercise, discusses ergogenic aids, and where possible, makes specific dietary recommendations for athletes.

Diet↗

Liquid flow across the epithelium of the artificially perfused lung of fetal and postnatal sheep.

1. The lungs of five fetal (133-140 days gestation) and thirty-four postnatal (2-240 days) sheep were artificially perfused in situ with warmed and oxygenated sheep blood. In postnatal animals the airspace of the lung was filled with liquid similar in composition to fetal lung liquid. In fetal and postnatal animals luminal liquid volume was measured by the impermeant tracer technique. 2. Under resting conditions the pulmonary epithelium of fetal animals secreted liquid at a mean (+/- S.E.M.) rate of 2.0 (+/- 0.4) ml (kg body weight)-1 h-1, those of postnantal animals absorbed liquid at -1.8 (+/- 0.2) ml (kg body weight)-1 h-1. 3. Addition of 2,4-dinitrophenol to achieve a concentration of 1.5 x 10(-3) M in the perfusing blood in postnatal animals caused complete cessation of liquid absorption. 4. Light and electron microscopic examination of the lung after periods of up to 6 h of artificial perfusion showed no evidence of epithelial damage. From 3 h onwards, liquid accumulation was evident in the perivascular spaces. 5. Addition of adrenaline to the perfusate in fetal animals caused absorption of liquid to occur at a mean rate of -2.9 (+/- 1.3) ml (kg body weight)-1 h-1. In postnatal animals adrenaline caused the rate of liquid absorption to increase from a mean rate of -1.4 (+/- 0.2) to -2.2 (+/- 0.3) ml (kg body weight)-1 h-1. 6. In the fetus addition of amiloride (0.8 x 10(-4) M) to the luminal fluid blocked adrenaline-induced liquid absorption and caused secretion to occur at 1.3 (+/- 0.3) ml (kg body weight)-1 h-1. 7. In postnatal animals the response to amiloride was age dependent. In newborn lambs (2-14 days) amiloride blocked liquid absorption and caused secretion of liquid to occur in seven out of eight animals at a mean rate of 0.9 (+/- 0.3) ml (kg body weight)-1 h-1 (n = 8). In older animals (15-240 days) the characteristic response to amiloride was slowing of the rate of liquid absorption (mean rate of absorption,-0.2 (+/- 0.09) ml (kg body weight)-1 h-1, n = 18) with liquid secretion being seen in only three of eighteen animals.(ABSTRACT TRUNCATED AT 400 WORDS)

2,4-Dinitrophenol↗

Physician's and dietitian's role in obese care.

In the Surgeon General's Report on Nutrition and Health, of the ten leading causes of death in the United States, five are nutrition related. Instead of nutritional deficiencies as seen in the 1940s, the national diet has shifted to dietary excesses and imbalances. Dietary excesses and imbalances are reflected in obesity, a major health problem affecting approximately 30% of the United States' population. Unfortunately, the diet industry is not regulated and, hence, patients have many avenues from which to choose. Many of these leave patients lost and confused as to why they have failed in maintaining their weight loss. It is well documented that the recidivism rate in the obese is high with only 5% maintaining their weight loss after one year. The following is a review of the physician's and dietitian's roles in long-term weight maintenance.

Dietetics↗

Community resources in obese care.

Community resources can augment care provided by physicians and dietitians for the obese. The well-distributed community resources in Florida are reviewed. They are well-established and provide emotional support, peer group dynamics, a variety of formats and prices, and information about food and life-style changes.

Humans↗

The acceptability of childhood immunization to Togolese mothers: a sociobehavioral perspective.

A study was conducted in Togo to investigate the lack of acceptance of childhood immunization from a social science perspective. In each village focus group interviews were conducted with approximately 12 mothers to discuss their beliefs and knowledge, social and cultural norms and practices, and experiences with health services that hinder or promote the acceptability of childhood immunization. The problem of failure to complete the immunization series was explained in terms of mothers' lack of knowledge of when to return or their forgetfulness rather than inadequate knowledge about the importance of returning. Other barriers included the requirement to keep and present a vaccination card, waiting time at the clinic, lack of information about available services, and laziness. Rather than endorsing strategies that target individuals, mothers suggested increasing the level of social control exerted by decision makers in their communities (the village chief could direct the town crier to announce the passing of each week to help parents keep track of time between immunizations) and increasing the level of social support by having a meeting to support the importance of completing the vaccination series and to organize mothers who go to the clinic to inform others in their neighborhoods about vaccination.

Costs and Cost Analysis↗

Synergistic action of triiodothyronine and hydrocortisone on epinephrine-induced reabsorption of fetal lung liquid.

The influence of triiodothyronine and hydrocortisone on maturation of the response to epinephrine that leads to reabsorption of lung liquid was investigated in nine chronically catheterized fetal sheep. Experiments were performed on thyroidectomized fetal sheep at 116-120 d gestation, well before the reabsorptive response to epinephrine is normally seen. After i.v. administration of either triiodothyronine (60 micrograms/d) or hydrocortisone (10 mg/d) for 3 d (three fetuses in each case), all fetuses continued to secrete lung liquid during exposure to epinephrine (secretion rate = 5.9 +/- 3.2 mL/h in triiodothyronine-treated and 4.4 +/- 1.9 mL/h in hydrocortisone-treated fetuses). However, when the two hormones were administered together in the same doses to three fetuses, a striking reabsorptive response to epinephrine was seen (absorption rate = -12.3 +/- 3.6 mL/h), similar to that observed in the mature fetus. Induction of this capacity to reabsorb lung liquid may be of importance in the management of respiratory problems of the newborn infant.

Absorption↗

Analysis of pre-rRNAs in heat-shocked HeLa cells allows identification of the upstream termination site of human polymerase I transcription.

Human rRNA precursor from normal or stressed HeLa cells were studied by S1 nuclease mapping of unlabeled RNA and by antisense RNase mapping of RNA from cells that had been labeled in vivo with [32P]PO4. Heating cells to 43 degrees C decreased the amount of newly synthesized rRNA to less than 5% of the control level and led to greater than 95% inhibition of transcription termination at a region 355 to 362 nucleotides downstream of the 3' end of 28S rRNA, with readthrough continuing into the next transcription unit. Heating of cells to 42 degrees C led to 60% inhibition of termination at this site; 50% of transcripts that extended into the nontranscribed spacer ended in a region 200 to 210 nucleotides upstream of the polymerase I (Pol I) initiation site. This is presumed to be the human upstream transcription termination site because of the absence of RNAs with a 5' end corresponding to this region, the location relative to the Pol I initiation site (which is similar to the location of upstream terminators in other species), and the fact that it is 15 to 25 nucleotides upstream of the sequence GGGTTGACC, which has an 8-of-9 base identity with the sequence 3' of the downstream termination site. Surprisingly, treatment of cells with sodium arsenite, which also leads to the induction of a stress response, did not inhibit termination. Pol I initiation was decreased to the same extent as termination, which lends support to the hypothesis that termination and initiation are coupled. Although termination was almost completely inhibited at 43 degrees C, the majority of the recently synthesized rRNAs were processed to have the correct 3' end of 28S. This finding suggests that 3'-end formation can involve an endonucleolytic cut and is not solely dependent on exonucleolytic trimming of correctly terminated rRNAs.

Animals↗

An in vitro interaction between the human U3 snRNP and 28S rRNA sequences near the alpha-sarcin site.

Model transcripts containing mammalian pre-rRNA sequences were incubated with a HeLa cell extract, digested with T1 RNase, and immunoprecipitated with anti-(U3)RNP or control antibodies. Two overlapping fragments derived from the 3' domain of human 28S rRNA were specifically immunoprecipitated although transcripts which spanned the transcription initiation site, the ETS processing site, the 5' end of 18S, and both termini of 5.8S yielded no protected fragments. The sequence of these fragments was determined using a novel technique in which the [32P]-labeled fragment was co-finger-printed with [3H]-labeled total transcript serving as an internal marker. The fragments immunoprecipitated derive from nucleotides 4570-4590 and 4575-4590 of human 28S and are adjacent to the alpha-sarcin site. Protection most likely involves the U3 RNA since it is sensitive to pretreatment of the extract with micrococcal nuclease. Complementarity between U3 and this rRNA region is phylogenetically conserved in species ranging from human to S. cerevisiae. The possible significance of this finding is discussed.

Antibodies↗

High level expression of heterologous proteins in methylotrophic yeast Pichia pastoris.

Expression of human tumor necrosis factor-alpha (TNF) and four different TNF analogs has been studied in Pichia pastoris by utilizing the alcohol oxidase gene promoter. TNF expression level in certain transformants accounted for as much as 36% of the soluble protein. TNF expression was stably maintained during high cell density fermentation (100 g dry cell weight/liter) resulting in a TNF production level of 6-10 g/liter. TNF contained in P. pastoris cell lysates was biologically active as determined by its cytotoxic effect on murine L-929 fibroblast cells and the bioactivity was retained for at least 6 months in the lysates stored frozen at -20 degrees C in the presence of protease inhibitor PMSF. TNF expressed in P. pastoris was recognized by monoclonal antibodies prepared against recombinant Escherichia coli derived TNF. TNF purified from P. pastoris has the expected N-terminal amino acid sequence and specific activity of 10(7) units/mg protein. TNF analogs were also expressed at levels comparable to that of native TNF. Three of the four analogs were insoluble when produced in P. pastoris.

Densitometry↗

Structural analysis of the human U3 ribonucleoprotein particle reveal a conserved sequence available for base pairing with pre-rRNA.

The human U3 ribonucleoprotein (RNP) has been analyzed to determine its protein constituents, sites of protein-RNA interaction, and RNA secondary structure. By using anti-U3 RNP antibodies and extracts prepared from HeLa cells labeled in vivo, the RNP was found to contain four nonphosphorylated proteins of 36, 30, 13, and 12.5 kilodaltons and two phosphorylated proteins of 74 and 59 kilodaltons. U3 nucleotides 72-90, 106-121, 154-166, and 190-217 must contain sites that interact with proteins since these regions are immunoprecipitated after treatment of the RNP with RNase A or T1. The secondary structure was probed with specific nucleases and by chemical modification with single-strand-specific reagents that block subsequent reverse transcription. Regions that are single stranded (and therefore potentially able to interact with a substrate RNA) include an evolutionarily conserved sequence at nucleotides 104-112 and nonconserved sequences at nucleotides 65-74, 80-84, and 88-93. Nucleotides 159-168 do not appear to be highly accessible, thus making it unlikely that this U3 sequence base pairs with sequences near the 5.8S rRNA-internal transcribed spacer II junction, as previously proposed. Alternative functions of the U3 RNP are discussed, including the possibility that U3 may participate in a processing event near the 3' end of 28S rRNA.

Animals↗