The Consumer Price Index (CPI).
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Economics↗
Biomedical subjects
P Stein
Publications and source records attributed to P Stein.
Serpin tertiary structure transformation.
Previous crystallographic analyses have demonstrated that proteolytic cleavage of the serpins can result in a dramatic transformation of their tertiary structure. Some 16 residues on the amino terminal side of the cleavage site are inserted into a large beta-sheet to become a central strand, separating the two cleaved residues by about 70 A. We have determined, in outline, the nature of the conformational change responsible for this transformation. After cleavage, a fragment of the protein, consisting of an alpha-helix and three strands of beta-sheet, moves away from the rest of the structure to make the space for the new strand. This movement involves a new type of structural change: sheet residues in the small fragment slide along grooves in an alpha-helix that belongs to the rest of the protein. The general conservation of residues in the regions between the small fragment and the rest of the protein imply that the same mechanism will be found in all serpins that undergo this tertiary structure transformation.
Amino Acid Sequence↗
Breast cancer. Risks, treatment, perioperative patient care.
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Breast Neoplasms↗
Progesterone production in cultured human granulosa cells: correlation with follicular fluid hormone levels.
STUDY OBJECTIVE: To examine the progesterone (P) production by cultured granulosa cells and the hormonal content in the follicular fluid (FF) of ovarian-hyperstimulated women. DESIGN: Retrospective. SETTING: Private Fertility Clinic and National Research Institute. PATIENTS: Eighteen patients undergoing in vitro fertilization or gamete intrafallopian transfer programs. RESULTS: Progesterone levels Measured in the culture medium of granulosa cells decreased sixfold with culture time. Human luteinizing hormone (LH) increased P production only when basal P production was less than 1 microgram/mL. Granulosa cell P production in culture was negatively correlated with FF LH-human chorionic gonadotropin (hCG) levels. Follicular fluid follicle-stimulating hormone (FSH) levels were positively correlated with FF P and 17 beta-estradiol (E2) concentrations. Similar results were found between FF LH (hCG) and E2 levels, but there was no relationship between FF LH (hCG) and FF P values. CONCLUSION: The high dose of hCG administered during gonadotropin treatment could induce a decrease in the in vitro granulosa cell P production.
Cells, Cultured↗
Epithelial dysfunction in nonbacterial cystitis (interstitial cystitis).
Traditional concepts of impermeability of the bladder have centered around unique cellular tight junctions and ion pumps. However, recent data from our laboratory have shown that the bladder epithelium in animals and humans relies primarily on its surface glycosaminoglycans to maintain its impermeability. This study demonstrates the first disease associated with an epithelial dysfunction of the bladder, that is a leaky epithelium. The study consisted of 31 normal subjects and 56 individuals with interstitial cystitis. Interstitial cystitis patients were shown to have a leaky epithelium by placing a solution of concentrated urea into the bladder and measuring the absorption. The normal subjects absorbed 4.3% in 45 minutes, while the interstitial cystitis patients absorbed 25% (difference is highly significant, p less than 0.005). Interstitial cystitis patients with Hunner's ulcers (10) had a 34.5% absorption rate, while those without ulcers absorbed 22.8% (46). This difference also was highly significant (p = 0.002) and supports the concept that patients with ulcers have clinically worse disease.
Absorption↗
Vitamins and trace metals status in non insulin dependent diabetes mellitus.
The status of various vitamins and trace metals in plasma of 100 Non Insulin Dependent Diabetes Mellitus subjects was compared to those of 112 age and sex matched healthy subjects. The plasma concentration of riboflavin, pyridoxine and folic acid were found to be decreased in the diabetic patients while retinol and ascorbic acid were relatively increased, in comparison to the healthy subjects. However in the Non Insulin Dependent Diabetes Mellitus subjects the mean plasma concentration of all the metals and vitamins except for riboflavin were within the range of normal values. In spite of these findings, the percent of diabetic patients with various vitamin or metal deficiencies, e.g. riboflavin, carotene, thiamin, retinol, zinc and iron were significantly higher than those in the healthy population. We conclude that vitamin and metal deficiency is common in Non Insulin Dependent Diabetes Mellitus subjects.
Adult↗
Perceptual responses and blood lactate concentration: effect of training state.
The present study investigated the effect of training state on ratings of perceived exertion obtained at the lactate threshold (LT) and fixed blood lactate concentrations (FBLC) of 2.0, 2.5, and 4.0 mM. Runners (N = 20) and nonrunners (N = 29) completed a progressive horizontal treadmill (TM) running test which allowed identification of the TM velocities associated with the LT and FBLC. Runners attained significantly higher TM velocities, greater VO2, greater VE, greater heart rate, and a lower ventilatory equivalent for oxygen (VE/VO2) at each exercise intensity, with the exceptions of heart rate at 4.0 mM and VE/VO2 at the LT. Compared to nonrunners, runners also attained higher VO2, VE, and heart rate relative to peak values at LT and 2.0, 2.5, and 4.0 mM. Despite these relative and absolute physiological differences, there were no differences between groups in local, central, or overall ratings of perceived exertion (RPE) (Borg scale) at any condition. The data from both groups were combined to give the following means and SD for overall RPE during horizontal running: at the LT-11.0 +/- 2.0, and at FBLC of 2.0 mM-13.7 +/- 2.1, 2.5 mM-14.5 +/- 1.8, and 4.0 mM-16.5 +/- 2.3.
Adult↗
Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy.
To examine the extent to which the defect in insulin action in subjects with non-insulin-dependent diabetes mellitus (NIDDM) can be accounted for by impairment of muscle glycogen synthesis, we performed combined hyperglycemic-hyperinsulinemic clamp studies with [13C]glucose in five subjects with NIDDM and in six age- and weight-matched healthy subjects. The rate of incorporation of intravenously infused [1-13C]glucose into muscle glycogen was measured directly in the gastrocnemius muscle by means of a nuclear magnetic resonance (NMR) spectrometer with a 15.5-minute time resolution and a 13C surface coil. The steady-state plasma concentrations of insulin (approximately 400 pmol per liter) and glucose (approximately 10 mmol per liter) were similar in both study groups. The mean (+/- SE) rate of glycogen synthesis, as determined by 13C NMR, was 78 +/- 28 and 183 +/- 39 mumol-glucosyl units per kilogram of muscle tissue (wet weight) per minute in the diabetic and normal subjects, respectively (P less than 0.05). The mean glucose uptake was markedly reduced in the diabetic (30 +/- 4 mumol per kilogram per minute) as compared with the normal subjects (51 +/- 3 mumol per kilogram per minute; P less than 0.005). The mean rate of nonoxidative glucose metabolism was 22 +/- 4 mumol per kilogram per minute in the diabetic subjects and 42 +/- 4 mumol per kilogram per minute in the normal subjects (P less than 0.005). When these rates are extrapolated to apply to the whole body, the synthesis of muscle glycogen would account for most of the total-body glucose uptake and all of the nonoxidative glucose metabolism in both normal and diabetic subjects. We conclude that muscle glycogen synthesis is the principal pathway of glucose disposal in both normal and diabetic subjects and that defects in muscle glycogen synthesis have a dominant role in the insulin resistance that occurs in persons with NIDDM.
Blood Glucose↗
Stature loss among an older United States population and its relation to bone mineral status.
Age-related statural loss has been recorded but incompletely assessed in modern populations. In this study, data collected on stature during annual bone mineral assessments are analyzed for 1,024 Caucasian individuals from southern Arizona. Continued stabilization in reported maximum heights is seen in this population. With advancing age there is a gradual decrease in height apparently beginning in the mid-40s. Thereafter, there is a relatively rapid decrease in measured height. This contrasts to the much slower rates predicted from earlier populations (Trotter and Gleser: American Journal of Physical Anthropology 9:311-324, 1951). The rate of stature loss is associated with diminution of bone mineral density as well as with maximum height. Since there are suggestions of a secular trend toward greater reductions in bone mineral density, this study suggests there may be a secular trend toward an increase in statural loss with age.
Age Factors↗
Effect of metformin treatment on insulin action in diabetic rats: in vivo and in vitro correlations.
The mechanism (both at the whole body and cellular level) by which metformin improves insulin sensitivity has yet to be defined. In the present study, we examined in vivo insulin-mediated whole-body glucose disposal, glycogen synthesis, hepatic glucose production, and insulin secretion, as well as in vitro muscle insulin receptor tyrosine kinase activity in eight control, eight neonatal streptozotocin diabetic rats, and eight diabetic rats before and after treatment with metformin. Ten weeks after birth diabetic rats had higher fasting (132 + 5 v 101 + 2 mg/dL) and postmeal (231 + 10 v 133 + 3) plasma glucose levels compared with controls (P less than .001). Metformin treatment was followed by a significant decrease in the growth rate and normalized glucose tolerance without enhancing the deficient insulin response. Insulin-mediated glucose uptake in diabetic versus control rats was reduced (P less than .01) during the high-dose (15.4 + 0.6 v 18.3 + 1.0 mg/kg.min) insulin clamp study and was increased to values greater (P less than .05) than controls following metformin treatment. Muscle glycogen synthetic rate in vivo, measured by incorporation of 3H-3-glucose radioactivity, was diminished by 25% (P less than .01) in diabetic rats, restored to normal values with metformin, and correlated closely (r = .82, P less than .002) with total-body glucose uptake during the insulin clamp in all three groups. Insulin receptor tyrosine kinase activity, measured in partially purified insulin receptors, was reduced in diabetic rats and increased to supernormal levels after metformin. The decrease in muscle tyrosine kinase activity in diabetic versus control animals was entirely accounted for by a reduction in maximal velocity (Vmax) (32 v 45 pmol/mg.min, P less than .01) and increased to supernormal levels following metformin (91 pmol/mg.min, P less than .001) without any change in affinity (Km). Muscle tyrosine kinase activity was closely correlated with both the muscle glycogen synthetic rate (r = .82, P less than .002) and total-body insulin-mediated glucose disposal (r = .64, P less than .01) in vivo. The close correlation between in vivo insulin action, muscle glycogen synthesis, and muscle insulin receptor tyrosine kinase activity is consistent with an important role of the enzyme in the insulin resistance of diabetes and its improvement following metformin treatment.
Animals↗
Inflammatory mediator release on conjunctival provocation of allergic subjects with allergen.
To evaluate the role of inflammatory mediators in the pathogenesis of the ocular allergic response, 23 subjects with positive histories of allergies to either cat dander or ragweed pollen and positive skin tests to the appropriate allergen extract were recruited and were subjected to conjunctival provocation. The tear duct of the left eye of each subject was blocked with a collagen plug while the right eye was left unplugged. In all cases, the eye was initially provoked with saline and subsequently with the appropriate allergen extract. Nonallergic subjects, or allergic subjects provoked with nonrelevant allergen, were used as control subjects. After each provocation, symptoms were recorded, and tears were collected with preweighed strips of filter paper (Schirmer strip). Each strip was placed into a tared tube containing fluid appropriate for the optimal preservation of the mediator to be measured. It was therefore possible to calculate the weight of tears collected and to express mediator levels per milliliter of tears. All allergic subjects demonstrated a positive symptomatic response to allergen challenge, whereas the control subjects remained asymptomatic. Blockage of the tear duct did not significantly alter the response. For allergic subjects, the levels of histamine, kinins, prostaglandin D2, albumin, and TAME-esterase activity were all significantly (p less than 0.005 in each case) greater after allergen challenge than after saline challenge. Furthermore, levels of each of these mediators after allergen challenge (expressed as increases above levels after saline provocation) were significantly greater for allergic subjects than for control subjects (p less than 0.005 in each case). Thus, the clinical response to conjunctival provocation with allergen is associated with increases in the levels of inflammatory mediators in tears.
Adolescent↗
Reliability and validity of a continuous incremental treadmill protocol for the determination of lactate threshold, fixed blood lactate concentrations, and VO2max.
Fifteen male runners were tested on two occasions to determine the reliability of a continuous incremental level running treadmill protocol (C), with 3-min stages, for lactate threshold (LT) and fixed blood lactate concentration (FBLC) (2.0 mM, 2.5 mM, 4.0 mM) assessment. Test-retest (T-RT) reliability coefficients for velocity at LT, 2.0 mM, 2.5 mM, and 4.0 mM were r = 0.89, 0.91, 0.95, and 0.95, respectively (velocity ranged from 215.3 m/min at LT to 273.6 m/min at 4.0 mM). Mean differences in T-RT velocity values ranged from 0.7 m/min (at LT) to 6.0 m/min (at 2.5 mM; 252.3 m/min vs 258.3 m/min; NS) and the standard errors of measurement were less than +/- 10.0 m/min. Similar results were observed for VO2, with T-RT r values ranging from r = 0.82 (at LT) to r = 0.88 (at 2.0 mM) (VO2 ranged from 47.2 ml/kg.min-1 at LT to 60.9 ml/kg.min-1 at 4.0 mM; VO2 peak = 65.6 ml/kg.min-1). Mean differences in T-RT VO2 values were less than 1.4 ml/kg.min-1 (NS) and the standard errors of measurement were less than +/- 2.95 ml/kg.min-1. Interinvestigator and intrainvestigator reliability coefficients were high and ranged from r = 0.91 to r = 0.99. Validity of C was assessed in an additional 16 male runners who completed C and a criterion discontinuous (D) protocol (using a series of 10-min stages) for LT and FBLC assessment. Results indicated that C and D resulted in similar VO2 and velocity values at LT and FBLC.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Laboratory valuation just how much is my laboratory worth? Establishing fair market value.
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Humans↗
Pharmacology of calcium release from sarcoplasmic reticulum.
Calcium release from sarcoplasmic reticulum (SR) has been elicited in response to additions of many different agents. Activators of Ca2+ release are here tentatively classified as activators of a Ca2+-induced Ca2+ release channel preferentially localized in SR terminal or as likely activators of other Ca2+ efflux pathways. Some of these pathways may be associated with several different mechanisms for SR Ca2+ release that have been postulated previously. Studies of various inhibitors of excitation-contraction coupling and of certain forms of SR Ca2+ release are summarized. The sensitivity of isolated SR to certain agents is unusually affected by experimental conditions. These effects can seriously undermine attempts to anticipate effects of the same pharmacological agents in situ. Finally, mention is made of a new preparation ("sarcoballs") designed to make the pharmacological study of SR Ca2+ release more accessible to electrophysiologists, and some concluding speculations on the future of SR pharmacology are offered.
Animals↗
[Computer-assisted urodynamics].
Advantages of computer assisted urodynamics with the "Urosoft" program (Wiest KG, Munich) are: Better Display with colormonitor and enhanced graphic adapter, a more rapid quantitative data evaluation, especially with larger data volumes, a better data storage and management, the possibility of program extension for scientific purposes, and the providing of a medical report. Disadvantages are additional costs for hard- and software, an individual time for familiarizing and adjustment and an additional expenditure in cases where only a qualitative evaluation is done. Important is a data analysis in a second step, not done automatically with the measurements, to eliminate artifacts.
Female↗
Oncogenous osteomalacia: a case study.
A case of oncogenous osteomalacia due to a fibrosarcoma of the maxilla is reported, with a 19 year course before treatment. Metabolic studies of calcium and phosphorus were performed 3 and 19 years after the first symptomology. There was a negative balance for both phosphorus and calcium with low serum levels of 1,25-dihydroxyvitamin D which were corrected by resection of the tumor. Portions of the tumor were cultured and the supernatant did not affect phosphorus transport by a proximal tubule kidney cell line. Other portions were injected into athymic nude mice where they resulted in hypophosphatemia and phosphaturia, thus confirming the endocrine nature of the oncogenous osteomalacia factor.
Adult↗
The porcine bioprosthetic heart valve: experience at 15 years.
The porcine bioprosthetic valve has been in use at Henry Ford Hospital since 1971. In this review, 980 patients with 1,081 porcine bioprosthetic valves were examined from 1 month to 16.4 years after implantation with a 99% complete follow-up. Patient survival was 59% +/- 2.2% (+/- standard error of the mean) at 10 years and 38% +/- 4.0% at 15 years. Factors associated with decreased survival after hospital discharge were age greater than 35 years and New York Heart Association functional class IV. Freedom from thromboembolism was 92% +/- 1.2% at 10 years and 89% +/- 3.2% at 15 years. Freedom from endocarditis was 93% +/- 1.2% at 10 years and 92% +/- 1.3% at 15 years. Freedom from structural valve degeneration for all valves was 71% +/- 2.6% at 10 years and 31% +/- 5.6% at 15 years. Factors associated with increased risk of structural valve degeneration were age younger than 35 years, female sex, and preoperative cardiac index greater than 2 L/min/m2. Among a total of 172 patients undergoing removal of a degenerated valve, mortality was 12.5%, and significant risk factors for death at reoperation were emergency operation and functional class IV. Experience with the porcine bioprosthetic valve after 15 years suggests that its use be confined to older patients or patients with a contraindication of anticoagulation.
Adolescent↗
Cycling of Ca2+ across the plasma membrane as a mechanism for generating a Ca2+ signal for cell activation.
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Calcium↗