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PubMedDate not supplied

Cytogenetic changes induced in human diploid fibroblasts by tsA58 SV40 at permissive and restrictive temperatures.

Human diploid fibroblasts have been transformed by ts A58 SV40. At the permissive temperature, apparent chromosome and chromatic rearrangements were observed in a high percentage of cells and the frequency of SCE increased. If the transformed phenotype returned to normal at the restrictive temperature these alterations also returned to normal levels. Chromosome banding demonstrated many apparent chromosomal rearrangements in which diffuse staining material was joining intact chromosomes end-to-end and forming pseudostructural abnormalities. Homogeneously staining regions associated with gene amplification or virus-induced alterations in the coiling and stickiness of telomeric regions are possible mechanisms.

Cell Transformation, Viral↗
PubMed1988

Metabolism of mutagenic polycyclic aromatic hydrocarbons by photosynthetic algal species.

Polycyclic aromatic hydrocarbons (PAH) known to produce carcinogenic and mutagenic effects have been shown to contaminate waters, sediments and soils. While it is accepted that metabolites of these compounds are responsible for most of their biological effects in mammals, their metabolism, and to a large extent their bioactivity, in aquatic plants have not been explored. Cultures of photosynthetic algal species were assayed for their ability to metabolize benzo[a]pyrene (BaP), a carcinogenic PAH under conditions which either permitted (white light) or disallowed (gold light) photooxidation of the compound. Growth of Selenastrum capricornutum, a fresh-water green alga, was completely inhibited when incubated in white light with 160 micrograms BaP/l medium. By contrast concentrations at the upper limit of BaP solubility in aqueous medium had no effect on algal growth when gold light was used. BaP quinones and phenol derivatives were found to inhibit growth of Selenastrum under white light incubation. BaP phototoxicity and metabolism were observed to be species-specific. All 3 tested species of the order Chlorococcales were growth-inhibited by BaP in white light whereas neither the green alga Chlamydomonas reinhardtii nor a blue-green, a yellow-green or an euglenoid alga responded in this fashion. Assays of radiolabeled BaP metabolism in Selenastrum showed that the majority of radioactivity associated with BaP was found in media as opposed to algal cell pellets, that the extent of metabolism was BaP concentration dependent, and that the proportion of various metabolites detected was a function of the light source. After gold light incubation, BaP diols predominated while after white light treatment at equal BaP concentrations, the 3,6-quinone was found in the highest concentration. Extracted material from algal cell pellets and from media was tested for mutagenicity in a forward mutation suspension assay in Salmonella typhimurium using resistance to 8-azaguanine for selection. Direct-acting mutagens were detected in extracted media from incubation of Selenastrum with 400 micrograms BaP/l for 1 day in gold light. Extracts of media from algae incubated in gold light from 1 to 4 days with 1200 micrograms BaP/l were found to have direct-acting mutagens as well as those requiring further metabolism. Media extracts from white light incubations of BaP were mutagenic upon addition of rat liver homogenates. Activity of these materials from white light treatment are largely attributable to unmetabolized BaP.

Benzo(a)pyrene↗
PubMed1977

Steroid structure and function:I. Conformational transmission in 17alpha-acetoxy progesterone.

The molecular conformation of 17alpha-acetoxy progesterone has been determined crystallographically and is compared with that of progesterone. The 17alpha-acetate substituent restricts the flexibility of the progesterone side chain, strains bond lengths in the C- and D-rings, and has long range effects on the A-ring conformation. The A-ring adopts a perfect sofa conformation similar to that observed in one conformational isomer of progesterone. Consequently this progesterone isomer is proposed to be that best suited to binding in the rabbit and human uterus.

Chemical Phenomena↗
PubMed1994

Application of quantitative computed tomography to Paget's disease of bone.

Serial evaluation of pagetic lesions is handicapped by the inability of conventional methods to reproduce precisely the positioning of the area of interest. A computed tomography method that provides visual and quantitative comparisons between data sets acquired at different times has been developed. The utility of this method is illustrated with an example of serial examinations that demonstrate the effect of treatment on small lytic lesions in the lumbar spine. A further demonstration is made of the ability of this method to identify and quantify lytic changes within the cochlear capsule.

Aged↗
PubMed1985

Primary muscle disease: definition of a 25-kDa polypeptide myopathic specific chagas antigen.

The sera from patients with primary heart and skeletal muscle diseases, hospitalized patients without intrinsic muscle disease from an area endemic for Trypanosoma cruzi infections, and normal subjects (N = 693) were studied for the presence of immunoglobulin G (IgG) antisarcolemma activity using serologic methods. The prevalence of elevated serum IgG antisarcolemma activity from patients with chronic Chagas' cardiomyopathy, idiopathic cardiomyopathy, polymyositis, and Duchenne muscular dystrophy was 58.9 +/- 10.4% (N = 101) (P less than 0.001 when compared to normal subjects). Two of twelve (16.7%) patients with acute T. cruzi infection and parasitemia developed elevated antisarcolemma titers, and 9/46 (19.6%) patients with chronic T. cruzi infection without evidence of cardiomyopathy yielded high antisarcolemma titers. On the other hand, patients with chronic T. cruzi infection with advanced cardiomyopathy yielded high antisarcolemma titers in 35/74 (47.3%) (P less than 0.001 when compared to normal subjects). Radioimmunoprecipitation showed a circulating antibody to a 25-kDa T. cruzi polypeptide (P25) in 16/17 (94.1%) patients with advanced cardiomyopathy and T. cruzi infection. No such antibody was shown in 12 asymptomatic subjects with chronic T. cruzi infection.

Antibodies↗
PubMed1990

Confocal imaging of ionised calcium in living plant cells.

Laser-scanning confocal microscopy has been used in conjunction with Fluo-3, a highly fluorescent visible wavelength probe for Ca2+, to visualize Ca2(+)-dynamics in the function of living plant cells. This combination has overcome many of the problems that have limited the use of fluorescence imaging techniques in the study of the role of cations (Ca2+ and H+) in plant cell physiology and enables these processes to be studied in single cells within intact plant tissue preparations. Maize coleoptiles respond to application of ionophores and plant growth hormones with elevations in cytosolic Ca2+ that can be resolved with a high degree of spatial resolution and can be interpreted quantitatively.

Aniline Compounds↗
PubMedDate not supplied

Measuring of impact of patient counseling in the outpatient pharmacy setting: development and implementation of the counseling models for the Kaiser Permanente/USC Patient Consultation Study.

The Southern California region Kaiser Permanente Medical Care Program, which serves 2.2 million patients, and the University of Southern California School of Pharmacy have designed and implemented a patient consultation study to determine the cost-effectiveness of three different approaches to providing pharmacist consultation to outpatients. This paper describes the development and implementation of these three models. A total of 107 pharmacies (approximately 600 pharmacists) participated in the study and were assigned to provide one of the models of patient consultation, designated the Kaiser Permanente (KP) model, the state model, and the control model. The KP model (20 pharmacies) provided targeted pharmaceutical care services to high-risk patients based on drug use. The state model (67 pharmacies) provided California-mandated patient consultation to patients with new or changed prescriptions, instructions for use, relevant warnings and precautions, storage requirements, and the importance of compliance. The control model (20 pharmacies) provided consultation when deemed necessary by the pharmacist and provided care similar to that provided before mandatory consultation in California. The KP and state models used the same pharmacist/technician/clerk resources, but the control pharmacies limited personnel resources to those existing before the mandatory consultation law was passed in California. The paper describes the KP model in detail and provides a literature-based rationale for targeting particular high-risk patients for expanded services. The paper also describes the training process, gives an example of a high-risk patient intervention, provides information on documenting pharmacist interventions in all models, and explains the method used for monitoring implementation of the models.

Ambulatory Care↗
PubMedDate not supplied

Measuring the impact of patient counseling in the outpatient pharmacy setting: the research design of the Kaiser Permanente/USC patient consultation study.

This article describes the research method used to measure the impact of three alternative models of patient counseling in the outpatient pharmacy setting. The study was conducted in pharmacies operated by the Southern California region Kaiser Permanente Medical Care Program. Both random assignment and large-scale geographic area research designs were used. The presentation of the research design includes discussions of data collection and patient sampling methods; the measurement of patient outcomes, including measures of health care costs and utilization, patient functional status, and quality of life. Demographic data are presented for the study population, including an analysis of potential biased selection of patients electing to participate in random assignment. Data are also presented documenting potential selection bias across geographically determined treatment groups in the geographic area design arm. Finally, the article presents the analysis plan for the study and discusses study limitations.

Ambulatory Care↗
PubMed1986

DNA-repair studies with sodium fluoride: comparative evaluation using density gradient ultracentrifugation and autoradiography.

Sodium fluoride (NaF) was assayed for the induction of DNA-repair synthesis in WI-38 human diploid fibroblasts and in primary cultures of rat hepatocytes. DNA-repair synthesis in non-replicating DNA was measured by ultracentrifugation of density-labeled DNA in CsCl gradients. When this method was used, NaF did not induce DNA-repair synthesis in either of these cell types. However, when NaF was assayed for induction of unscheduled DNA synthesis (UDS) in rat hepatocytes by autoradiography, an increased net nuclear grain count was observed. Because the autoradiographic results were not confirmed by density-gradient ultracentrifugation of hepatocyte DNA, which is a more definitive technique, it is doubtful whether the autoradiographic results actually represent DNA-repair synthesis. Modifications of the UDS/autoradiography protocol to include more extensive washing resulted in no UDS response. Published reports (Hellung-Larsen and Klenow, 1969; Srivastava et al., 1981) describe the formation of precipitable complexes of Mg2+, F-, and [3H]thymidine triphosphate which suggests that autoradiographic measurement of UDS may lead to artifacts when testing NaF unless extensive washing of the cultures is employed.

Animals↗
PubMed1989

Genotoxicity of zinc in 4 short-term mutagenicity assays.

The genotoxicity of zinc was examined in 4 short-term mutagenicity assays. Zinc acetate produced dose-related positive responses in the L5178Y mouse lymphoma assay and an in vitro cytogenetic assay with Chinese hamster ovary cells, but was negative in the Salmonella mutation assay and did not induce unscheduled DNA synthesis in primary cultures of rat hepatocytes. Zinc-2,4-pentanedione produced frameshift mutations in Salmonella tester strains TA1538 and TA98, but did not induce unscheduled DNA synthesis in primary cultures of rat hepatocytes. The effect of ligand binding of zinc in the in vitro test systems is discussed.

Animals↗
PubMed1993

Stretch reflexes of individual parkinsonian patients studied during changes in clinical rigidity following medication.

Stretch reflexes were elicited in flexor carpi radialis (FCR) of healthy subjects and patients with Parkinson's disease by forcible ramp and hold extensions of the wrist joint. Individual patients were studied off treatment when rigidity was detected clinically at the joint and throughout the clinical response to anti-parkinsonian medication that abolished or reduced their rigidity. In this way the possible effects of inter-subject variability upon the relationship between reflex behaviour and rigidity were eliminated. The long-latency (M2) stretch reflexes of the patient group were increased on average compared to those of healthy subjects. However, in the large majority of individual patients there were no significant correlations between the amplitudes of their M2 or total (short-latency (M1) + M2) reflex activities, recorded off and on treatment, and the accompanying changes in clinically assessed rigidity. These results suggest that parkinsonian rigidity cannot be uniquely attributed to the increased reflex responsiveness measured by the present laboratory techniques. However, the techniques used to test reflex function in our study differed in several respects (e.g., background activity, stretching wave form) from those employed during clinical assessment of rigidity so that the balance of reflex mechanisms may have varied in the two situations. Therefore, these results cannot be taken as definitive evidence against a reflex origin of rigidity.

Aged↗
PubMed1993

Increased dependence upon visual information of movement performance during visuo-motor tracking in cerebellar disorders.

The effect of temporarily suppressing the visual display of either the target (desired) trajectory or the actual movement trajectory upon the accuracy of visuo-motor tracking was studied in 6 patients with cerebellar syndromes and 6 healthy subjects. Subjects made extension and flexion movements of the wrist to superimpose a cursor displaying their actual movement (movement cursor) upon one indicating the target (target cursor) on a VDU screen. The target trajectory consisted of a sawtooth pattern of slow (4 deg/sec) ramp extension and instantaneous flexion return phases. Following practice, the tracking of cerebellar patients was significantly less accurate than that of healthy subjects for each phase (P = 0.02). Temporary suppression of the movement cursor during both the mid-section of the ramp phase (P = 0.05) and around the reversal phase (P = 0.04) caused a significant increase in tracking errors in the patients whereas suppression of the target cursor did not alter their performance. Suppression of neither cursor altered the tracking accuracy of healthy subjects during the ramp extensions whilst suppression of either caused reduced (P = 0.02) performance for the reversal phase. We interpret the increased dependence of patients upon visual information of their movements during slow trajectories as indicating an impairment of proprioceptive guidance.

Adult↗
PubMedDate not supplied

Relative stability of alpha-melanotropin and related analogues to rat brain homogenates.

alpha-Melanotropin (alpha-MSH) retains less than 1% of its original activity after a 60 min incubation with 10% rat brain homogenate. [Nle4,D-Phe7]-alpha-MSH is nonbiodegradable in rat serum (240 min incubation) and still maintains 10% of its original activity in 10% rat brain homogenate (240 min incubation). The related fragment analogue, Ac-[Nle4,D-Phe7]-alpha-MSH4-10-NH2, retains 50% of its activity after a 240 min incubation in rat brain homogenate, whereas Ac-[Nle4,D-Phe7]-alpha-MSH4-11-NH2 is totally resistant to inactivation by rat brain homogenate. Both [Nle4,D-Phe7]-fragments are resistant to degradation by rat serum, but [Nle4]-alpha-MSH, Ac-[Nle4]-alpha-MSH4-10-NH2 and Ac-[Nle4]-alpha-MSH4-11-NH2 are rapidly inactivated under both conditions. The cyclic melanotropin, [Cys4,Cys10]-alpha-MSH, is inactivated in rat brain homogenate as is the shorter Ac-[Cys4,Cys10]-alpha-MSH4-10-NH2 analogue, but neither cyclic melanotropin is inactivated upon incubation in serum from rats. Ac-[Cys4,D-Phe7,Cys10]-alpha-MSH4-10-NH2 is resistant to inactivation by either rat serum or a brain homogenate. Some of these melanotropin analogues may provide useful probes for the localization and characterization of putative melanotropin receptors in both the central nervous system and peripheral tissues.

Animals↗
PubMedDate not supplied

Structural and conformational modifications of alpha-MSH/ACTH4-10 provide melanotropin analogues with highly potent behavioral activities.

Previous studies have identified the (4-10) heptapeptide sequence as the central core of alpha-MSH/ACTH peptides required for mediation of important biological activities. In the present study, the structure-activity relationships of Nle4-substituted and Cys4,Cys10-bridged cyclic alpha-MSH analogues, which were previously shown to exhibit a wide range of melanotropic potencies from weak agonism to super potency, were examined for grooming behavioral activity in the rat following intracerebroventricular injections. The results showed that stepwise C-terminal elongation of the linear Nle4-substituted Ac-alpha-MSH4-10-NH2 increased grooming potencies of the peptides in a manner similar to their actions on melanocytes. The most interesting finding was the observation that cyclization of the inactive linear "central (4-10) core" of alpha-MSH (Ac-alpha-MSH4-10) to form Ac-[Cys4,Cys10]-alpha-MSH4-10-NH2 resulted in a super potent agonist in the grooming assay. However, while cyclization of the (4-10) heptapeptide produced potent agonists on grooming behavior, the structure-activity relationships were different than the frog skin bioassay. These findings support the hypothesis that appropriate structural and confirmational modifications of alpha-MSH-related peptides can produce profound effects on the bioactivities of the peptides, and suggest that different structural-conformational requirements exist for alpha-MSH interactions with its various receptors.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Alpha-melanocyte stimulating hormone message and inhibitory sequences: comparative structure-activity studies on melanocytes.

We investigated the structure-activity relationships of alpha-MSH (alpha-melanocyte stimulating hormone) fragment derivatives of the generic formulae Ac-alpha-MSH(x-13)-NH2 and Ac-alpha-MSH(6-x)-NH2. The minimal C-terminal sequences required for melanotropic activity were 8-13 and 7-13, respectively, in the frog and lizard skin bioassays. The Arg8-Trp9 sequence appears to be a fundamental component of the minimal message sequences found to date such as alpha-MSH(6-9), alpha-MSH(8-13) and alpha-MSH(7-13). We discovered that Ac-alpha-MSH(7-10)-NH2 was a weak and selective alpha-MSH antagonist on the lizard skin bioassay. Analysis of alpha-MSH(7-10) analogues of the generic formula Ac-Xaa-Arg-Trp-Yaa-NH2 led to Ac-[D-Trp7,D-Phe10]alpha-MSH(7-10)-NH2, a moderately potent, specific and competitive inhibitor of alpha-MSH in both the frog and the lizard skin bioassays.

Amino Acid Sequence↗
PubMed1995

Interdialytic weight gain and nutritional parameters in chronic hemodialysis patients.

The extent of interdialytic weight gain (IDWG) in chronic hemodialysis patients is usually attributed to the level of compliance with fluid restriction. However, in view of the substantial water content of food (and caloric content of beverages), IDWG also may be a function of calorie and protein intake and may reflect the nutritional state of patients. To investigate this theory, the relationship between 2-day IDWG and body weight, normalized protein catabolic rate (nPCR), serum albumin, and delivered Kt/V urea was assessed in a prospective, randomized study of 860 chronic hemodialysis patients in 56 dialysis units. Compared with patients having < 2 kg IDWG (n = 378), patients with > 3 kg IDWG (n = 138) weighed more (dry weight, 76.8 v 61.7 kg), had higher nPCR (1.15 v 0.96 g/kg/d), and had higher serum albumin levels (3.96 vs 3.79 g/dL) (all P < 0.001) but did not have different levels of Kt/V (1.04 v 1.06). When IDWG was assessed as a function of dry weight, patients with IDWG > 4.5% of dry weight (n = 151) had higher nPCR (1.17 v 0.94 g/kg/d) but weighed less (60.1 v 70.0 kg) and had a higher Kt/V (1.14 v 1.01) than patients with IDWG < 3% of dry weight (n = 355) (all P < 0.001). Artifactual association between IDWG and nPCR attributable to an accentuated two-pool effect from differing ultrafiltration requirements was unlikely as assessed by the relationship between modeled Kt/V and prescribed Kt/V determined using an anthropometric urea volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary Proteins↗