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Biomedical subjects

R S Phillips

Publications and source records attributed to R S Phillips.

At least 199 records · Page 11Linked to original sources
PubMed1988

Mechanistic deductions from multiple kinetic and solvent deuterium isotope effects and pH studies of pyridoxal phosphate dependent carbon-carbon lyases: Escherichia coli tryptophan indole-lyase.

Analysis of the pH dependence of the kinetic parameters and competitive inhibitor Ki values for tryptophan indole-lyase suggests two enzymic groups must be unprotonated in order to facilitate binding and catalysis of tryptophan. The V/K for tryptophan and the pKi for oxindolyl-L-alanine, a putative transition state analogue and competitive inhibitor, decrease below two pK values of 7.6 and 6.0, while the Ki for L-alanine, also a competitive inhibitor, is 3300-fold larger (20 mM) than that for oxindolyl-L-alanine and increases below a single pK of 7.6. A single pK of 7.6 is also observed in the V/K profile for the alternate substrate, S-methyl-L-cysteine. Therefore, the enzymic group with a pK of 7.6 is responsible for proton abstraction at the 2-position of tryptophan, while the enzymic group with a pK of 6.0 interacts with the indole portion of tryptophan and probably catalyzes formation of the indolenine tautomer of tryptophan (in concert with proton transfer to C-3 of indole from the group with pK 7.6) to facilitate carbon-carbon bond cleavage and elimination of indole. The pH variation of the primary deuterium isotope effects for proton abstraction at the 2-position of tryptophan (DV = 2.5 and D(V/Ktrp) = 2.8) are pH independent, while the Vmax for tryptophan or S-methyl-L-cysteine is the same and also pH independent. Thus, substrates bind only to the correctly protonated form of the enzyme. Further, tryptophan is not sticky, and the pK values observed in both V/K profiles are the correct ones.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1988

6-Nitro-L-tryptophan: a novel spectroscopic probe of trp aporepressor and human serum albumin.

The binding of 6-nitro-L-tryptophan to trp aporepressor and human serum albumin has been examined by visible difference spectroscopy and circular dichroism. 6-Nitro-L-tryptophan, prepared by nitration of L-tryptophan with nitric acid in glacial acetic acid, exhibits a visible and near-uv absorption spectrum with lambda max at about 330 nm (epsilon = 7 X 10(3) M-1 cm-1) and a shoulder near 380 nm in H2O. In the presence of trp aporepressor, the visible absorption intensity is sharply diminished. Visible difference spectral titration data give KD = 1.27 X 10(-4) M and n = 0.95 per subunit at 25 degrees C. While 6-nitro-L-tryptophan exhibits no significant circular dichroism between 300 and 500 nm, the complex with trp aporepressor exhibits strong circular dichroism signals, with a negative maximum at 386 nm (delta epsilon = -7.5 M-1 cm-1) and a positive maximum at 310 nm (delta epsilon = +6 M-1 cm-1). Circular dichroism titration data give KD = 1.69 X 10(-4) M and n = 0.90 per subunit at 25 degrees C. The KD values determined spectroscopically are in excellent agreement with that determined by equilibrium dialysis, KD = 1.5 X 10(-4) M at 25 degrees C. In the presence of human serum albumin, the spectrum of 6-nitro-L-tryptophan exhibits a blue shift and an increase in absorption intensity; similar changes are observed in solvents of low dielectric contrast such as 80% aqueous dioxane. Visible difference spectral titration data give KD = 8.0 X 10(-5) M and n = 0.95 for human serum albumin. The complex of 6-nitro-L-tryptophan with human serum albumin exhibits a strong positive circular dichroism maximum at 380 nm (delta epsilon = +9.8 M-1 cm-1) with a shoulder at 310-320 nm. Circular dichroism titration data give KD = 6.4 X 10(-5) M and n = 0.83, in good agreement with the visible difference spectral results. Taken together, our results demonstrate the utility of 6-nitro-L-tryptophan as a spectroscopic probe for tryptophan-binding proteins.

Algorithms↗
PubMed1988

Gonorrhea in women seen for routine gynecologic care: criteria for testing.

PURPOSE: This study was initiated to determine risk factors for Neisseria gonorrhoeae infection of the cervix in women seen for routine care in a hospital-based obstetrics and gynecology practice. PATIENTS AND METHODS: Extensive clinical data and cervical culture specimens for N. gonorrhoeae were obtained prospectively from 1,441 women between the ages of 18 and 50. Fifty clinical factors were evaluated by multivariate analysis. RESULTS: Of the 1,441 patients tested, 25 (1.7 percent) had a positive culture result. The majority of infected women were asymptomatic. The following five factors were found to be associated independently with gonococcal infection: (1) sex with a partner who may have had gonorrhea or a urethral discharge within the prior three months, (2) endocervical bleeding induced by the initial swab, (3) age at first intercourse less than or equal to 16, (4) method of payment (Medicaid), and (5) low abdominal or pelvic pain. Race, a univariate risk factor, was not associated with gonorrhea when these other factors were considered. The risk of infection for women with none, one, two, or three or more of these multivariate risk factors was 0.2, 0.8, 2.9, and 9.8 percent, respectively. CONCLUSION: Clinical data are helpful in identifying women at risk for gonorrhea. If resources are insufficient to evaluate all sexually active women, we suggest routine testing based on the presence of the multivariate risk factors identified.

Adolescent↗
PubMed1988

Identification of factors associated with the diagnosis of delirium in elderly hospitalized patients.

We analyzed factors associated with the discharge diagnosis of delirium among 1,285 patients admitted to a major teaching hospital during a 2-year period, developed a model to classify the risk of developing delirium on the basis of clinical and diagnostic data, and tested the model on 471 patients admitted during the subsequent year. Using the multivariate technique of recursive partitioning, we identified four factors that distinguished 80% of all cases of delirium: 1) a urinary tract infection at any time during the hospital stay (odds ratio = 3.1; 95% confidence interval = 2.02-4.58); 2) no urinary tract infection, but low serum albumin on admission (odds ratio = 2.4; 95% confidence interval = 1.43-3.99); 3) neither urinary tract infection nor low serum albumin, but elevated white blood cell count on admission (odds ratio = 1.99; 95% confidence interval = 1.18-3.37); 4) none of these risk factors, but proteinuria on admission (odds ratio = 1.82; 95% confidence interval = 1.25-2.66). Patients without any of these four risk factors had the lowest probability of developing delirium during their hospital stay. Among individuals with delirium, in-hospital mortality and hospital charges were higher. The model developed accurately characterized the risk of delirium when it was tested on patients admitted to the same hospital during the subsequent year.

Aged↗
PubMed1988

The effects of morbid obesity and the Garren-Edwards gastric bubble on solid phase gastric emptying.

Rapid solid phase gastric emptying (SPGE) resulting in decreased satiety is postulated to be a contributing factor to obesity. Twenty-six morbidly obese patients with a weight range of 189-523 lb were entered into the Garren-Edwards gastric bubble program. SPGE studies were performed pre-bubble implantation and repeated within 2 wk after bubble implant. There was no significant difference between study patients pre-bubble insertion emptying time and the normal population curve. Emptying time was found to be significantly increased, post-bubble implant, compared with pre-bubble implant over five time periods of testing. The Garren-Edwards gastric bubble has been used as a method for inducing early satiety for the morbidly obese patient. It has been postulated that delay of SPGE would be associated with satiety. Our patients experienced satiety despite their more rapid SPGE. Thus, the satiety which was experienced by our subjects was not on the basis of delayed SPGE, as previously thought.

Adolescent↗
PubMed1988

Age as a risk factor in colonoscopy: fact versus fiction.

Age has been assumed to be an independent risk factor in patients undergoing colonoscopy. However, this has never been specifically studied. We evaluated 302 patients 65 yr old or older, to determine the incidence of complications. We found that the risk is comparable to that of the heterogeneous patient population previously reported, except for a slightly increased incidence of delayed bleeding subsequent to polypectomy. In addition, the presence of cardiac, pulmonary, liver, or kidney disease was not found to be associated with an increased incidence of complications. Neither was there an increased risk of complications in patients undergoing colonoscopy, who had previously undergone abdominal or pelvic surgery. In summary, older patients experience the same risks as younger patients, except for post-polypectomy delayed bleeding, which may be related to atherosclerosis of the blood vessels, and appears to be more common in elderly patients.

Age Factors↗
PubMed1988

Effects of gastric bubble implant on weight change with and without compliance with a behavior modification program.

The purpose of this prospective study was to evaluate the effect of compliance versus noncompliance with a behavior modification program (BMP) for 35 patients who underwent implantation of 51 Garren-Edwards gastric bubbles (GEGB). Criteria for morbid obesity was met by every patient. Two patient groups were formed by self-selection. Compliant patients (group I) attended 75% or more of the BMP. Group II consisted of noncompliant patients, and was divided further into partially complaint and totally noncompliant. A significant difference was found in both loss of weight and loss of body mass index (BMI) between the complaint and noncompliant groups, with no significant difference in weight loss between the partially and totally noncompliant groups. Patients' compliant or noncompliant behavior had a significant effect on changes in weight (p = 0.007) and body mass index (p = 0.005). Sixteen patients had two consecutive bubble implants. The rate of compliance was significantly higher during the first implant program, with a significantly greater loss in both weight and BMI for compliant patients. Follow-up data for 28 of 35 patients revealed a continued, albeit small, average weight decrease. In summary, weight loss does not result from the gastric bubble alone. Our study demonstrates that the key factor is compliance with a behavior modification program.

Adolescent↗
PubMed1987

Purine-metabolizing enzymes in Babesia divergens.

Extracts of Babesia divergens were examined for the enzymes which catalyse purine salvage. Adenosine deaminase (EC 3.5.4.4), guanine deaminase (EC 3.5.4.3), inosine phosphorylase (EC 2.4.2.1), purine phosphoribosyltransferases (EC 2.4.2.7, EC 2.4.2.8, EC 2.4.2.22) and nucleoside kinases (EC 2.7.1.15, EC 2.7.1.20, EC 2.7.1.73) were all detected at relatively high activities, whereas nucleotide interconverting enzymes were not detected. Coformycin and 4-amino-5-imidazolecarboxamide were found to be potent inhibitors of adenosine deaminase and guanine deaminase, respectively. The results suggest that B. divergens is capable of synthesizing purine nucleotides via two routes, one involving purine phosphoribosyltransferases and the other employing nucleoside kinases.

Animals↗
PubMed1987

Reactions of O-acyl-L-serines with tryptophanase, tyrosine phenol-lyase, and tryptophan synthase.

The reactions of tryptophanase, tyrosine phenol-lyase, and tryptophan synthase with a new class of substrates, the O-acyl-L-serines, have been examined. A method for preparation of O-benzoyl-L-serine in high yield from tert.-butyloxycarbonyl (tBoc)-L-serine has been developed. Reaction of the cesium salt of tBoc-L-serine with benzyl bromide in dimethylformamide gives tBoc-L-serine benzyl ester in excellent yield. Acylation with benzoyl chloride and triethylamine in acetonitrile followed by hydrogenolysis with 10% palladium on carbon in trifluoroacetic acid gives O-benzoyl-L-serine, isolated as the hydrochloride salt. O-Benzoyl-L-serine is a good substrate for beta-elimination or beta-substitution reactions catalyzed by both tryptophanase and tyrosine phenol-lyase, with Vmax values 5- to 6-fold those of the physiological substrates and comparable to that of S-(o-nitrophenyl)-L-cysteine. Unexpectedly, O-acetyl-L-serine is a very poor substrate for these enzymes, with Vmax values about 5% of those of the physiological substrates. Both O-acyl-L-serines are poor substrates for tryptophan synthase, measured either by the synthesis of 5-fluoro-L-tryptophan from 5-fluoroindole and L-serine catalyzed by the intact alpha 2 beta 2 subunit or by the beta-elimination reaction catalyzed by the isolated beta 2 subunit. With all three enzymes, the elimination of benzoate appears to be irreversible. These results suggest that the binding energy from the aromatic ring of O-benzoyl-L-serine is used to lower the transition-state barrier for the elimination reactions catalyzed by tryptophanase and tyrosine phenol-lyase. Our findings support the suggestion (M. N. Kazarinoff and E. E. Snell (1980) J. Biol. Chem. 255, 6228-6233) that tryptophanase undergoes a conformational change during catalysis and suggest that tyrosine phenol-lyase also may undergo a conformational change during catalysis.

Catalysis↗
PubMed1987

Experience with diagnostic laparoscopy in a hepatology training program.

Laparoscopy is an underutilized endoscopic procedure in the United States even though it has proven to be an important diagnostic modality. Among factors that may account for the unpopularity of this procedure are lack of experience and proper training in many gastroenterology fellowship programs, a perceived notion that there is a relatively high complication rate, and the preference for radiologic imaging techniques for establishing a diagnosis. We reviewed, over an 11-month period, our experience with laparoscopy in a large teaching center to better assess its safety when performed by trainees. The major and minor complication rates were 0.9% and 2.9%, respectively, with no fatalities. These findings compare favorably with the general experience.

Adolescent↗
PubMed1987

The effect of mosquito transmission of antigenic variants of Plasmodium chabaudi.

Plasmodium chabaudi AS strain in mice is characterized by an acute primary parasitaemia, and one or more less acute recrudescences. Previous work has shown, using a passive protection assay, that the recrudescent parasites are usually antigenically different from parasites of the parent population with which the mice were first infected. In this study the effect of mosquito transmission on the antigenic expression of recrudescent populations of P. chabaudi was examined. In the first experiments the recrudescent population which was antigenically different from the parent population was uncloned. After transmission through Anopheles stephensi the recrudescent population appeared to revert to an antigenic type similar to that of the parent population. In the second experiment clones from a recrudescent population were mosquito transmitted and again the parasites of the primary patent parasitaemia in the mice, bitten by the infected mosquitoes, had reverted to the parental type. It is suggested that antigenic variants of P. chabaudi AS strain may revert to a basic type after mosquito transmission.

Animals↗
PubMed1987

Use of a direct fluorescent antibody test for detecting Chlamydia trachomatis cervical infection in women seeking routine gynecologic care.

We determined the sensitivity, specificity, and predictive value of a direct fluorescence test for Chlamydia trachomatis infection compared with culture of the endocervix in women seeking routine gynecologic care. Of 527 patients seen in a hospital-based practice, 23 (4.4%) had a positive culture for C. trachomatis. The overall sensitivity of the direct test was 70%, and the specificity was 98%. When five or more endocervical cells were present on the direct test slide, the sensitivity increased to 92%, and the specificity decreased to 96% (P less than .05). When the presence of any columnar epithelial cells, five or more elementary bodies, or both was used as the criteria for accepting specimens, the sensitivity and specificity of the direct test were 80% and 96%, respectively. However, 44% of the specimens would be rejected if these criteria were used. The overall probability that an individual with a positive direct test would have a positive culture was 62%.

Adult↗