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PubMed1995

Evaluation of atopy through an expert system: description of the database.

BACKGROUND: In order to understand the medical decisions taken during the initial visit of a new asthmatic patient, a group of experts designed an expert system which provides conclusions about severity, precipitating factors and treatment. Rules for atopy and the assessment of allergic factors have been discussed and implemented in the expert system. Conclusions about severity have been yet validated using an appropriate methodology. OBJECTIVE: The aim of this study was to investigate a sample of 471 patients according to conclusions regarding atopy. METHODS: A total of 471 cases report forms (CRF) was filled in for adult asthmatic outpatients, seen for the first time in our clinic without emergency situations. Data of each CRF were used by the expert system to draw conclusions. The expert system discerns three patterns for atopy, yes, possible or no. The variables known to reflect different features according to the classification of asthma as atopic or not have been studied. The variables used in the rules for atopy, obviously linked to the conclusion, were not compared. For many medical problems no unique objective solution exists and this is why a group of patients with possible atopy was introduced. RESULTS: Patients with atopy had less severe asthma (P = 0.01), a better FEV1 value (P = 0.0007) and showed their first symptoms of asthma earlier (P = 0.00001) than patients without atopy. CONCLUSIONS: The characteristics of the group studied here are consistent with the literature. This could be considered as an indirect validation of the expert system. Moreover, patients with possible atopy show intermediate findings for these variables and it is possible to suggest a 'dose-effect' relationship.

Adolescent↗
PubMed1986

Arthroscopic landmarks of the equine carpus.

The radiocarpal and middle carpal joints of 4 clinically normal horses and 24 necropsy specimens were examined with an arthroscope to describe the topographic anatomy of these joints. The carpal bones of the radiocarpal joint had congruent articular surfaces in extension, but carpal flexion resulted in a stairstep between the radial and intermediate carpal bones. The variable surface anatomy, as well as the restricted synovial space and the technical limitations of the arthroscope, contributed to the need for more than one arthroscopic approach to the radiocarpal joint to ensure a thorough examination. The middle carpal joint's hinge-like biomechanics resulted in a spacious synovial cavity that was more amenable to arthroscopic examination. Careful planning was necessary to ensure that areas of interest were distant from the arthroscope-insertion site to allow the best perspective possible. The lateral approach to the middle carpal joint provided the best viewing of both facets of the intermediate and third carpal bones as well as the dorsal rim of the radial carpal bone. The medial approach did not allow complete inspection of these areas.

Animals↗
PubMed1988

Neuroendocrine carcinomas of the colon and rectum: a clinicopathologic evaluation.

Neuroendocrine carcinomas were diagnosed in 13 of 683 patients who had colon cancers removed from January 1980 to June 1987 for an incidence of 1.9%. The patients were 28 to 89 years of age (median, 72 years). There were seven male and six female patients. The treatment was as follows: right hemicolectomy, 5; transverse colectomy, 1; left hemicolectomy, 1; low anterior resection, 2; abdominal-perineal resection, 1; and in 3 patients with rectal tumors, biopsy examination only was performed. Microscopic stages were as follows: Dukes' stage B, 1; stage C, 6; stage D, 5; and stage indeterminate, 1. By light microscopy, the tumors showed solid clusters or ribbons of round to fusiform, small to intermediate-sized cells with variably abundant mitoses. Eight tumors had foci of glandular and/or squamous differentiation. By immunohistochemistry, all tumors showed one or more neuroendocrine markers, including neuron-specific enolase, chromogranin, synaptophysin, serotonin, and various neuropeptides. By electron microscopy, single membrane-bound neurosecretory granules were noted. The sites of metastases included regional nodes, 8; liver, 5; bone, 1. Four patients were treated with a combination of chemotherapy and radiation therapy. These tumors were, as a group, aggressive, with eight patients dead within 12 months of diagnosis. Median survival was 7 months, with three patients alive at 2, 38, and 68 months, respectively. Specifically, small- and intermediate-cell neuroendocrine carcinomas of the colon and rectum behaved very aggressively and displayed numerous structural and functional similarities with their bronchopulmonary counterparts.

Adult↗
PubMed1989

Lifetime calcium intake and physical activity habits: independent and combined effects on the radial bone of healthy premenopausal Caucasian women.

Lifetime calcium intake and lifetime physical activity (PA) habits of 181 healthy premenopausal Caucasian women (aged 20-50) were studied. Nondominant arm was measured by single-photon absorptiometry at the distal (Dis) or 5-mm site and the midshaft (Mid) or two-thirds site of the radius. Values of bone mineral content (BMC), bone width (BW), and bone mineral density (BMD) were obtained. An intermediate or high lifetime Ca (greater than 500 mg/d) was significantly associated with a greater DisBMC (p = 0.0031), DisBMD (p = 0.0031), MidBMC (p = 0.0015), and MidBMD (p = 0.0015) when adjusted for PA. Similarly, with Ca adjusted for, a high lifetime PA (greater than or equal to 45 min of moderate to strenuous activity four times a week) was significantly associated with greater DisBMC (p = 0.0032), DisBMD (p = 0.0022), MidBMC (p = 0.0012), MidBW (p = 0.0173), and MidBMD (p = 0.0546). These findings suggest important roles for both adequate Ca intake and PA habits in enhancing peak adult skeletal mass and a trade-off between these two variables, when each was intermediate or higher.

Adult↗
PubMedDate not supplied

[Comparative value of temperature marker and neutralization test for subtyping of herpes simplex viruses (author's transl)].

Two methods for the differentiation of herpes simplex virus (HSV)--rct and neutralization by specific antisera--have been applied to 8 prototype strains and 105 strains isolated from various clinical cases. The evaluation of the II/I index allows to choose the most specific rabbit antisera. The rct 40 degrees 3 C marker test gives comparable results for HSV grown in RK13 and human fibroblasts as well; it is in agreement with the immunological test in 48% of the cases. The delta tc values used to express the immunological typing allow to differentiate 76% of the strains (types 1 and 2). The others (24%) are equally neutralized by both specific antisera; they represent "intermediate" strains. The infection of man and animal by HSV (type 1, 2 or "intermediate") also produces heterospecific antibodies in variable amount. From clinical and immunological data rises the hypothesis that "intermediate" strains derive from HSV1 strains by antigenic variation during a persistent infection.

Animals↗
PubMed1999

Performance and physiological variables in broiler chicken lines differing in susceptibility to the ascites syndrome: 1. Changes in blood gases as a function of ambient temperature.

1. Male broilers of 5 genetic stocks (A, B, C, D, E) selected in different ways for fast growth and low food conversion ratio (FCR) and differing in ascites sensitivity were subjected to 2 different ambient temperature step down regimens: high temperature (HT: 33 to 20 degrees C over 33 d) and low temperature (LT: 30 to 15 degrees C over 17 d). 2. Ascites incidence was recorded daily. Food intake and body weight gain were measured weekly and FCR was calculated. Heat production (Hp) was calculated using the comparative slaughter method. At 28 d venous samples were taken for blood gas analysis and haematocrit and relative heart, lung and liver weights were recorded. 3. Populations A and C showed the highest growth rates combined with a low FCR and a higher ascites incidence. A low FCR in these stocks was attributable to low values for Hp. These stocks also had low PO2 and high pCO2 in venous blood at low ambient temperature compared with other stocks. Stock B, which exhibited the slowest growth rate and the highest FCR, was not susceptible to ascites and showed higher Hp and PO2 and pCO2 at low ambient temperature. Populations D and E were intermediate for almost all variables. Heart and lung weights were both increased at LT, while liver weight did not differ between temperature regimes. 4. Our results show that a high haematocrit is not necessarily linked with an increased susceptibility to ascites.

Animals↗
PubMed1992

IgG subclass responses to Theiler's murine encephalomyelitis virus infection and immunization suggest a dominant role for Th1 cells in susceptible mouse strains.

Inbred mouse strains differ in susceptibility to Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease. A strong correlation between disease susceptibility and delayed-type hypersensitivity (DTH) has been previously demonstrated, but no strong correlation between disease susceptibility and total anti-TMEV ELISA titres was shown. Since both DTH and IgG2a antibody production are regulated by CD4+ Th1 cells, we investigated three strains of mice to determine whether antivirus IgG2a antibody levels, like DTH in previous studies, correlated with disease susceptibility. Susceptible SJL/J, intermediately susceptible C3H/HeJ, and resistant C57BL/6 mice were infected intracerebrally (i.c.) with the BeAn strain of TMEV and monitored for clinical signs of demyelination and for levels of TMEV-specific antibody of different IgG subclasses using a particle concentration fluorescence immunoassay (PCFIA). Resistant C57BL/6 mice were found to have significantly lower concentrations of total anti-TMEV antibody than susceptible SJL/J mice and intermediately susceptible C3H/HeJ mice show variable antibody responses. A predominance of anti-TMEV IgG2a (Th1 regulated) antibody was seen in susceptible and intermediately susceptible mice, whereas resistant mice displayed a predominant anti-TMEV IgG1 (Th2 regulated) response accompanied by a marked deficiency of IgG2a. In contrast, immunization of C57BL/6 mice with UV-inactivated TMEV in adjuvant revealed that this strain was not defective either in its ability to generate high levels of anti-TMEV antibody or in its ability to produce IgG2a antibody. These results suggest that the antivirus IgG subclass profile is dependent upon the immunization route, virus viability and/or the use of adjuvant and that the levels of antivirus subclasses may be predictive of disease susceptibility.

Animals↗
PubMed2002

Variable K(+) channel subunit dysfunction in inherited mutations of KCNA1.

Mutations of KCNA1, which codes for the K(+) channel subunit hKv1.1, are associated with the human autosomal dominant disease episodic ataxia type 1 (EA1). Five recently described mutations are associated with a broad range of phenotypes: neuromyotonia alone or with seizures, EA1 with seizures, or very drug-resistant EA1. Here we investigated the consequences of each mutation for channel assembly, trafficking, gating and permeation. We related data obtained from co-expression of mutant and wild-type hKv1.1 to the results of expressing mutant-wild-type fusion proteins, and combined electrophysiological recordings in Xenopus oocytes with a pharmacological discrimination of the contribution of mutant and wild-type subunits to channels expressed at the membrane. We also applied confocal laser scanning microscopy to measure the level of expression of either wild-type or mutant subunits tagged with green fluorescent protein (GFP). R417stop truncates most of the C-terminus and is associated with severe drug-resistant EA1. Electrophysiological and pharmacological measurements indicated that the mutation impairs both tetramerisation of R417stop with wild-type subunits, and membrane targeting of heterotetramers. This conclusion was supported by confocal laser scanning imaging of enhanced GFP (EGFP)-tagged hKv1.1 subunits. Co-expression of R417stop with wild-type hKv1.2 subunits yielded similar results to co-expression with wild-type hKv1.1. Mutations associated with typical EA1 (V404I) or with neuromyotonia alone (P244H) significantly affected neither tetramerisation nor trafficking, and only altered channel kinetics. Two other mutations associated with a severe phenotype (T226R, A242P) yielded an intermediate result. The phenotypic variability of KCNA1 mutations is reflected in a wide range of disorders of channel assembly, trafficking and kinetics.

Animals↗
PubMed2001

Beta-carotene redox reactions in photosystem II: electron transfer pathway.

A carotenoid (Car), a chlorophyll (Chl(Z)), and cytochrome b(559) (Cyt b(559)) are able to donate electrons with a low quantum yield to the photooxidized chlorophyll, P680(+), when photosystem II (PSII) is illuminated at low temperatures. Three pathways for electron transfer from Cyt b(559) to P680(+) are considered: (a) the "linear pathway" in which Cyt b(559) donates via Chl(Z) to Car, (b) the "branched pathway" in which Cyt b(559) donates via Car and where Chl(Z) is also able to donate to Car, and (c) the "parallel pathway" where Cyt b(559) donates to P680 without intermediate electron carriers and electron donation from Chl(Z) and Car occurs by a competing pathway. Experiments were performed using EPR and spectrophotometry in an attempt to distinguish among these pathways, and the following observations were made. (1) Using PSII with an intact Mn cluster in which Cyt b(559) was preoxidized, Car oxidation was dominant upon illumination at < or =20 K, while electron donation from Chl dominated at >120 K. (2) When Cyt b(559) was prereduced, its light-induced oxidation occurred at < or =20 K in what appeared to be all of the centers and without the formation of a detectable Car(+) intermediate. The small and variable quantity of Car(+) photoinduced in these experiments can be attributed to the residual centers in which Cyt b(559) remained oxidized prior to illumination. (3) The relative rates for irreversible electron donation from Cyt b(559) and Car were determined indirectly at 20 K by monitoring the flash-induced loss of charge separation (i.e., the accumulation of Cyt b(559)(+)Q(A)(-) or Car(+)Q(A)(-)). Similar yields per flash were observed (13% for Cyt b(559) and 8% for Car), indicating similar donation rates. The slightly lower yield with Car as a donor is attributed at least in part to slow charge recombination occurring from the Car(+)Q(A)(-) radical pair in a fraction of centers. (4) Light-induced oxidation of Cyt b(559) and Car at 20 K was monitored directly by EPR, and the rates were found to be indistinguishable. The parallel pathway predicts that when both Cyt b(559) and Car are prereduced, the relative amounts of Cyt b(559)(+) and Car(+) produced upon illumination at 20 K should depend directly on their relative electron donation rates. The measured similarity in the donation rates thus predicts comparable yields of oxidation for both donors. However, what is observed experimentally is that Cyt b(559) oxidation occurs almost exclusively, and this argues strongly against the parallel pathway. The lack of Car(+) as a detectable intermediate is attributed to rapid electron transfer from Cyt b(559) to Car(+). The trapping of Car(+) at low temperature when Cyt b(559) is preoxidized but its absence when Cyt b(559) is prereduced is taken as an argument against the simple linear pathway. Overall, the data reported here and previously favor the branched pathway over the linear pathway, while the parallel pathway is thought to be unlikely. Structural considerations provide further arguments in favor of the branched model.

Carotenoids↗
PubMedDate not supplied

Variability in the enzyme properties of Pseudomonas aeruginosa strain 2x oxidizing p-xylene.

A culture of Pseudomonas aeruginosa 2x was observed for its spontaneous variability for growth on p-xylene and the intermediate products of its metabolism. The highest variability was found for ability to grow on p-xylene and pyrocatechol, and a variability an order of magnitude lower was found for ability to grow on protocatechuate and p-toluate. No variability was found for the character "ability to grow on p-hydroxybenzoate." The activity of the key enzymes for the oxidation of p-xylene was studied in p-xylene-negative strains. The difference between the p-xylene-positive wild type strain and the spontaneous p-xylene-negative strains was found to be linked to changes in the regulatory mechanisms for several enzymes: p-xylene methylhydroxylase and the enzymes involved in the breakdown of the aromatic ring. In addition, the appearance of p-xylene-negative strains was linked with a significant fall in the specific activity of all enzymes, except pyrocatechuase, which was replaced by metapyrocatechuase on a number of substrates.

4-Hydroxybenzoate-3-Monooxygenase↗
PubMedDate not supplied

Proliferation and maturation indices in nephrogenic rests and Wilms tumor; the emergence of heterogeneity from dormant nodular renal blastema.

Independent nephrogenic rests (NRs) accompany many Wilms tumors (WTs), exhibit a range of qualities suggesting dormancy, maturation, regression, and hyperplasia, and may carry the WT-1 mutation. We assessed nucleolar organizer regions, proliferating cell nuclear antigen (PCNA) activity, cytoplasmic filament expression, and nuclear morphology in 79 nephrogenic rests accompanying 20 WTs. We found a direct relationship between the size of a blastematous NR and the AgNOR number per nucleus and a close correlation with PCNA activity. The blastema of most NRs > 1 cm in diameter was indistinguishable from blastema of most WTs. The smallest NR usually had a low number of silver-reactive nucleolar organizing regions (AgNORs), low PCNA activity, and absent cytoplasmic filaments, all characteristics of a nascent dormant state in which both proliferation rate and protein synthetic activity are low. Intermediate filament expression was variable in blastema of larger NRs; cytoplasmic filaments correlated with emergence of epithelial maturation and absence of filaments with accumulation of immature cells; mature epithelial structures in NRs had low AgNOR number and PCNA activity representing a terminal dormant state. The majority of blastemal cells in most WTs and in one-third of large hyperplastic NRs lack cytoplasmic filaments. This, plus the occasional finding in large NRs of features more typical of WTs such as prevalence of apoptosis, patches of frank necrosis, multinodular architecture, and expanses of monomorphic, poorly vascularized blastema with low PCNA activity, suggest that it may be possible to distinguish NRs that are progressing toward WT from those that are merely hyperplastic. This study refines the concepts of dormancy and hyperplasia as expressed in NRs and provides a general framework for probing the relationship of molecular events to progression of a small proportion of NRs to WT. Criteria used herein to define dormancy and hyperplasia may be useful in assessing lesions other than typical WT, such as unusually large or extensive NRs or uncommon differentiated WTs where the potential for aggressive behavior may be lower than in usual WTs.

Adrenal Rest Tumor↗
PubMed1997

Natural history and clinical management of central retinal vein occlusion. The Central Vein Occlusion Study Group.

OBJECTIVE: To provide clinical management guidelines for eyes with central retinal vein occlusion. DESIGN: Prospective cohort study with randomized clinical trials of specific subgroups of patients. Three-year follow-up every 4 months. SETTING: Nine ophthalmology practices. PATIENTS: Seven hundred twenty-five patients with central vein occlusion. MAIN OUTCOME MEASURES: Iris neovascularization (INV), neovascular glaucoma, and visual acuity. RESULTS: Visual acuity outcome was largely dependent on initial acuity. Sixty-five percent of patients with initially good visual acuity (20/40 or better) maintained visual acuity in the same range at the end of the study. Patients with intermediate initial acuity (20/50-20/200) showed a variable outcome: 19% improved to better than 20/50, 44% stayed in the intermediate group, and 37% had final visual acuity worse than 20/200. Patients who had poor visual acuity at the first visit (< 20/200) had an 80% chance of having a visual acuity less than 20/200 at final visit, whether perfused or nonperfused initially. In the first 4 months of follow-up, 81 (15%) of the 547 eyes with perfusion converted to ischemia. During the next 32 months of follow-up, an additional 19% of eyes were found to have converted to ischemia for a total of 34% after 3 years. The development of nonperfusion or ischemia was most rapid in the first 4 months and progressed continuously throughout the entire duration of follow-up. Iris neovascularization of at least 2-clock hours, and/or angle neovascularization (ANV) developed in 117 (16%) of the 714 eyes. Sixty-one of the 117 eyes that had INV/ANV were initially categorized as nonperfused or indeterminate; 56 of the 117 eyes were initially categorized as perfused. When INV/ANV occurred, it was treated promptly with panretinal photocoagulation. The strongest predictors of INV/ANV were visual acuity (P < .001) and the amount of nonperfusion seen by fluorescein angiogram (P < .001). For eyes initially categorized as nonperfused or indeterminate, 35% (61/176) developed INV/ANV, compared with 10% (56/538) for eyes initially categorized as perfused. Other risk factors were venous tortuosity (P = .02), extensive retinal hemorrhage (P = .07), and duration less than 1 month (P = .08). Neovascular glaucoma that was unsuccessfully managed with medical treatment developed in only 10 eyes. No eye was enucleated. CONCLUSIONS: Visual acuity at baseline is a strong predictor of visual acuity at 3 years for eyes with good vision and eyes with poor vision, but a poor predictor for intermediate acuities. Visual acuity is also a strong predictor for the development of INV/ANV, as is nonperfusion. During the course of follow-up, one third of the eyes with perfusion converted to eyes with ischemia. Clinical management guidelines, developed from these and previously reported Central Vein Occlusion Study data, are presented.

Aged↗
PubMed1990

Effects of acculturation and age on the exercise capacities of Solomon Islanders.

Submaximal exercise tests were carried out on 197 females and 290 males from five populations in the Solomon Islands to determine how acculturation affects the fitness of different age and sex groups. Males and females in the least acculturated group show the highest fitness levels, reflecting strenuous work patterns. Subjects from the most acculturated groups exhibit the lowest levels of fitness, a consequence of their more sedentary life-styles. Unexpectedly, older females in these groups show exercise capacities that are equal to those of younger women. This may be a consequence of generational differences in the practice of traditional activities, such as those associated with gardening. Groups ranked intermediate in acculturation show variable patterns. For some age and sex groups, modernization has reinforced and even intensified strenuous activity patterns, resulting in high levels of fitness. For others, modernization has promoted inactivity and/or altered dietary patterns, resulting in increased body fat and low levels of fitness.

Acculturation↗
PubMed1995

Longitudinal study on the production of and cellular response to interleukin-2 in patients with systemic lupus erythematosus.

Interleukin-2 (IL-2) has been proven to be a defective element in immune regulation in systemic lupus erythematosus (SLE). However, its course in time is unknown. We studied its production and cellular response in the peripheral blood cells of 30 SLE patients and 12 healthy subjects. In addition, we studied the spontaneous and lipopolysaccharide (LPS) induced production of IL-1, which have been found to be, respectively, increased and lowered in untreated SLE patients. Patients were studied at the outset, when still untreated, and at 1, 2, 6, 12, 18, and 24 months. At the outset, 18 had active disease and 12 were in remission. The decreased proliferative response of T cells to IL-2 and the deficient production of IL-1 upon LPS induction became normal after 6 months treatment, whereas the expression of high affinity IL-2 receptors took 18 months to become normal and the deficient production of IL-2 took 2 years. Despite clinical remission, the decreased capacity of T cells to absorb IL-2 persisted for 2 years. The effect of various prednisone dosages on the measured variables was evaluated. With intermediate doses of prednisone (20-45 mg), we observed the largest improvement in IL-2 production and in IL-1 production upon LPS stimulation. Higher doses of prednisone reduced also the spontaneous production of IL-1 and resulted in an increase in the expression of CD25+ cells. The addition of low doses of cytotoxic drugs (oral cyclophosphamide or azathioprine) resulted in an improvement in the capacity to absorb IL-2 and a reduction in spontaneous IL-1 production.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2003

Swimming ability and behaviour of post-larvae of a temperate marine fish re-entrained in the pelagic environment.

The degree to which behaviour, vertical movement and horizontal transport, in relation to local hydrodynamics, may facilitate secondary dispersal in the water column was studied in post-larval Sillaginodes punctata in Port Phillip Bay, Australia. S. punctata were captured in shallow seagrass beds and released at the surface in three depth zones (1.5, 3 and 7 m) off-shore at each of two sites to mimic the re-entrainment of fish. The behaviour, depth and position of S. punctata were recorded through time. The direction and speed of local currents were described using an S4 current meter and the movement of drogues. Regardless of site, fish immediately oriented toward the bottom, and into the current after release. In shallow water (1.5 m), 86% of fish swam to the bottom within 2 min of release. At one site, the net horizontal displacement of fish was largely unrelated to the speed and direction of local currents; at a second site, fish could not maintain their position against the current, and the net horizontal displacement was related to the speed and direction of currents. In the intermediate depth zone, wide variability in depths of individual fish through time led to an average depth reached by fish that was between the shallow and deep zones. Based on daily increments in the otoliths, however, this variability was not related significantly to the time since entry of fish into Port Phillip Bay. In the deepest depth zone, 81% of fish remained within 1 m of the surface and their horizontal displacement was significantly related to the direction and speed of currents. Secondary dispersal of post-larval fish in the water column may be facilitated by the behaviour and vertical movements of fish, but only if fish reach deeper water, where their displacement (direction and distance) closely resembles local hydrodynamic regimes. In shallow water, fish behaviour and vertical migration actually reduce the potential for secondary dispersal.

Adaptation, Physiological↗
PubMed1989

Defining the structural requirements for a helix in 23 S ribosomal RNA that confers erythromycin resistance.

The helix spanning nucleotides 1198 to 1247 (helix 1200-1250) in Escherichia coli 23 S ribosomal RNA (rRNA) is functionally important in protein synthesis, and deletions in this region confer erythromycin resistance. In order to define the structural requirements for resistance, we have dissected this region using in vitro mutagenesis. Erythromycin resistance is established after a minimal deletion of three bases, CAU1231 or AUG1232. The maximum deletion observed to confer resistance is 25 bases. The level of erythromycin resistance conferred by intermediate sized deletions is variable and some deletion mutants show a sensitive phenotype. Deletions that extend into the base-pairing between GCC1208 and GGU1240 result in non-functional 23 S RNAs, which consequently do not confer resistance. A number of phylogenetically conserved nucleotides have been shown to be non-essential for 23 S RNA function. However, removal of either these or non-conserved nucleotides from helix 1200-1250 measurably reduces the efficiency of 23 S RNA in forming functional ribosomes. We have used chemical probing and a modified primer extension method to investigate erythromycin binding to wild-type and resistant ribosomes with a 12-base deletion in 23 S RNA. Erythromycin interacts as strongly with mutant 23 S RNA as with wild-type 23 S RNA. Deletions in the 1200-1250 helix do not therefore confer resistance by reducing erythromycin binding, but by suppressing the effects of the drug at the level of its mechanism of action.

Base Sequence↗
PubMed1978

Cocaine reinforced progressive ratio performance in the rhesus monkey.

A series of experiments were conducted to determine the effectiveness of a progressive ratio (PR) procedure in measuring the relative reinforcing efficacy of several intravenous doses of cocaine. In Experiment 1, utilizing much smaller increases in the ratio requirement than previously reported, the animals generally displayed increases in breaking point with increases in the cocaine unit dose up to 0.4 mg/kg/inj. The highest dose studied (0.8 mg/kg/inj.) engendered breaking points lower than the 0.4 mg/kg dose but higher than the remaining lower doses. Experiment 2 was conducted utilizing the same reinforcement schedule as in Experiment 1 but with liquid Tang as the reward. The results demonstrated that this procedure would function to discriminate reinforcing strength with a more traditional reward. Experiment 3 examined a more expedient procedure to see if results similar to those seen in Experiment 1 could be obtained in a shorter period of time. However, the shorter procedure engendered excessive intrasubject variability, suggesting that some intermediate level of baseline experience between the 5-7 days used in Experiment 1 and the 50 reinforced responses used in Experiment 3 would be necessary to obtain consistent breaking point-unit dose functions.

Animals↗
PubMed1992

Cytogenetics of multiple endocrine neoplasia syndrome. II. Chromosome abnormalities in an insulinoma and a glucagonoma from two subjects with MEN1.

Cytogenetic analysis of two pancreatic islet tumors, an insulinoma and a glucagonoma was ascertained in two subjects with multiple endocrine neoplasia type 1 (MEN1). The insulinoma had a modal peak at 84 chromosomes. Most cells were pseudotetraploid, and in all cells the normal chromosomes were represented in varied numbers, i.e., from 1 to 7 copies. The tumor had 5 characteristic and consistent marker chromosomes which were identified as deletions of chromosomes 1, 2, 7, 16, and 17. All metaphases had several double minute chromosomes (dmin) of variable size and possible intermediate structures between dmin and homogeneously staining chromosomal regions. The glucagonoma had a nearly equal proportion of normal metaphases and metaphases with structural and numerical abnormalities with no consistent trend.

Chromosome Aberrations↗