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Biomedical subjects

S S Smith

Publications and source records attributed to S S Smith.

At least 145 records · Page 8Linked to original sources

Progesterone alters GABA and glutamate responsiveness: a possible mechanism for its anxiolytic action.

In this study, the neuromodulatory effects of progesterone were tested in an intact neuronal circuit of a model extrahypothalamic CNS area. Spontaneous discharge and responses of single cerebellar Purkinje neurons to microiontophoretically applied gamma-aminobutyric acid (GABA) and glutamate were monitored before, during and after either systemic injection, at physiologic doses, or local application of the steroid. By both means of administration, progesterone significantly enhanced inhibitory responses of Purkinje cells to GABA and suppressed glutamate excitation within 3-10 min post-steroid. These results are consistent with the anxiolytic actions of the steroid.

Animals↗

A paradigm for determination of direct drug-induced modulatory alterations in Purkinje cell activity during treadmill locomotion.

This paper describes a paradigm employing chronic single unit recording techniques and videotape analysis of treadmill locomotion in order to determine drug-induced modulation of sensorimotor neuronal activity. Animals implanted with a chronic headstage microdrive unit and an indwelling jugular cannula are trained to walk on a treadmill (10 s on, 10 s off). Characteristically, cerebellar Purkinje cells recorded 1-1.5 mm from midline, exhibit increased rates of discharge in phase with movement of specific limbs during a particular stage of the step-swing cycle, as assessed by video analysis of locomotor patterns. Drug-induced alterations in this movement-correlated discharge relative to changes in the spontaneous firing rate can then be determined to assess drug-induced neuromodulatory effects beyond general non-specific excitatory or inhibitory actions.

Action Potentials↗

Locally applied progesterone metabolites alter neuronal responsiveness in the cerebellum.

Ongoing studies in this laboratory have demonstrated that both systemically and locally administered sex steroids 17 beta estradiol (E2) and progesterone (P) alter cerebellar Purkinje cell responses to microiontophoretically applied amino acid neurotransmitters GABA and glutamate (GLUT) in the urethane-anesthetized, ovariectomized adult rat. In the present study, we have examined the effects of several locally pressure ejected P metabolites on Purkinje cell responsiveness to GABA and GLUT: 5 alpha-pregnane-20-one (5 alpha DHP), 5 alpha-pregnane-3 alpha-ol-20-one (3 alpha OH-DHP) and 5 alpha-pregnane-3 beta-ol-20-one (3 beta OH-DHP). GABA-induced inhibition was markedly enhanced immediately after onset of local application of 3 alpha OH-DHP or 5 alpha DHP, unaccompanied by alterations in background discharge. Both metabolites also attenuated excitatory responses to GLUT by 0-3 min after initiation of steroid application. In both cases, recovery to control levels of response was observed 6-9 min after termination of pressure application. These results are similar to those seen after local or systemic injection of P. In contrast, 3 beta OH-DHP did not produce any alteration in Purkinje cell responses to either amino acid. As 5 alpha DHP and 3 alpha OH-DHP can be localized in cerebellar tissue after P administration, the results presented here suggest that the neuronal effects of systemic P may be mediated by local membrane actions of P or its metabolites.

Animals↗

Computerized system for quantitative measurement of sensorimotor aspects of human performance.

The purpose of this article is to describe an integrated system for measuring selected aspects of human sensorimotor performance. The system consists of a computerized test battery, a database, and multiple software packages to present results for different applications. The system includes measures classified into major functional categories including sensation, range of motion, isometric muscle strength, anthropometric features, speed, reactions, muscle tone, coordination, body stability, and manual dexterity. A microcomputer is used to coordinate basic measurements obtained from a series of short-duration tests. Raw data are recorded in physical units (eg, degrees, milliseconds). A database currently consisting of over 2,000 data records of normal sensorimotor performance has been collected, permitting immediate comparison of patient data to a group of age- and sex-matched norms. This system permits an objective, reliable, and standardized method for measuring selected aspects of sensorimotor performance essential for physical therapists to quantify individual patient performance, document disability, justify reimbursement, screen employees and athletes, and demonstrate efficacy of treatment.

Activities of Daily Living↗

Selective phosphorylation of human DNA methyltransferase by protein kinase C.

Human DNA methyltransferase, the enzyme thought to be responsible for the somatic inheritance of patterns of DNA methylation, is an effective substrate for phosphorylation by protein kinase C. This provides a plausible mechanistic link between the action of tumor promoting phorbol esters, which stimulate protein kinase C, and abnormal patterns of DNA methylation often observed in transformed cells.

Calcium↗

Patient education financing under Medicare.

This paper traces the history of Medicare policies and practices with respect to reimbursement for preventive health care services and examines future propositions and trends for such reimbursement to hospitals and physicians. The discussion focuses on fee-for-service reimbursement under Medicare Part B (Supplementary Medical Insurance). Reimbursement under Part A (Hospital Insurance) for outpatient diabetes education is also described. The types of services and circumstances for which Medicare Part B provides reimbursement are explained. The paper describes a variety of outpatient preventive clinical and educational services that are reimbursable when ordered by a physician for diagnosis of a suspected illness or pathology or for treatment of same. The importance of the manner of claim presentation to Medicare carriers or intermediaries is emphasized. The concluding sections examine reimbursement for inpatient hospital education under Medicare Part A in light of the growing impact of the prospective pricing system's diagnosis-related groups (DRGs). The influence of the Tax Equity and Fiscal Responsibility Act on Medicare beneficiaries' enrollment in health maintenance organizations is recognized, and implications of the prospective payment system for health education practitioners are outlined.

Insurance, Physician Services↗

Neonatal release of gonadotropins is essential for development of ovarian follicle-stimulating hormone receptors.

In the rat, ovarian follicle-stimulating hormone (FSH) receptors increase markedly during the first two postnatal weeks, when serum gonadotropin levels are most elevated. This study was conducted to evaluate the hypothesis that these high gonadotropin levels, and in particular FSH, are involved in the acquisition of FSH receptors by the developing ovary. Gonadotropin release was suppressed by administration of several non-aromatizable androgens, among which dihydrotestosterone propionate (DHTP) was the most effective. In one series of experiments the steroids were administered from Days 5 to 11, and serum FSH and luteinizing hormone (LH) were measured on Day 12. Surprisingly, FSH receptor content was greater in rats with suppressed serum gonadotropins than in controls. The greatest increase in available receptors was observed in DHTP-treated rats in which serum FSH was reduced to 20% of control values and LH suppressed to undetectable values. DHTP failed to directly increase available FSH receptors in hypophysectomized immature rats. Magnesium chloride (MgCl2) treatment of ovarian membranes removed bound 125I-hFSH by 87% without affecting receptor viability. Exposure of control 12-day-old ovaries to MgCl2 increased available FSH receptors to a level similar to that of ovaries from DHTP-treated rats not exposed to MgCl2, suggesting that more receptors were available in DHTP-treated rats because serum FSH was suppressed. Earlier initation of DHTP treatment (postnatal Day 1) suppressed serum FSH and LH to undetectable values by Day 5 and decreased FSH receptor content below control values by Day 12. MgCl2 treatment only slightly increased available receptors in these DHTP-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗

Evaluation of a blood-free, charcoal-based, selective medium for the isolation of Campylobacter organisms from feces.

A blood-free, charcoal-based selective medium (CSM) consisting of a Columbia agar base, activated charcoal (4 g/liter), hematin (0.032 g/liter), sodium pyruvate (0.1 g/liter), cefoperazone (32 mg/liter), vancomycin (20 mg/liter), and cycloheximide (100 mg/liter) supported the growth of Campylobacter jejuni and C. coli with colony counts equivalent to those obtained on antibiotic-free horse blood agar. CSM was compared to Skirrow medium (SKM) for the recovery of C. jejuni and C. coli from stools of patients with diarrhea, the media being incubated for 2 days under reduced oxygen tension at 43 degrees C. These campylobacters were isolated from 35 (2.9%) of 1,227 stools tested (29 on both media, 5 on CSM alone, and one on SKM alone). Whenever C. jejuni and C. coli were recovered, growth was pure on 29 CSM cultures (85%), but on only 11 SKM cultures (37%). Complete suppression of "contaminating" flora occurred in 704 CSM cultures (57%) compared with 426 SKM cultures (35%). CSM more effectively suppressed contaminating pseudomonads, gram-positive organisms, and yeasts than did SKM; both media failed to suppress members of the family Enterobacteriaceae in about a quarter of the samples. Studies on 20 representative Enterobacteriaceae contaminants showed that susceptibility to cefoperazone and growth on CSM were markedly dependent on inoculum size; 12 strains were inhibited by cefoperazone (32 mg/liter) at inoculum sizes of 5 X 10(2) and 5 X 10(4) but not 5 X 10(6) organisms, indicating that the frequency of contaminants on CSM could probably be reduced further by ensuring that stools were not inoculated too heavily on CSM. Our findings confirm that charcoal is an effective substitute for blood in media for growing campylobacters, and that CSM is a highly effective blood-free selective medium for isolating C. jejuni and C. coli from stools.

Agar↗

Presence of luteinizing hormone releasing hormone (LHRH) in milk.

Evidence is presented a luteinizing hormone-releasing hormone (LHRH)-like substance exists in milk of the rat and that this substance is transferred to the offspring during suckling. This milk "LHRH" generates an inhibition curve parallel to authentic LHRH in the LHRH radioimmunoassay (RIA) and coelutes, to a significant extent, with LHRH upon Sephadex G-25 chromatography. An increase in LHRH-like immunoreactivity (LHRH-LI) can be detected in both the stomach and plasma of infantile rats during suckling. Available ovarian LHRH receptors increase in the pups after separation of the mother and return to basal values following suckling. This change is prevented by i. v. administration of an LHRH antiserum. Milk LHRH stimulates gonadotropin release in vitro and inhibits both gonadotropin-induced steroid secretion from granulosa cells in culture and the binding of LHRH to ovarian membranes.

Animals↗

Purification of human DNA (cytosine-5-)-methyltransferase.

We have developed a facile procedure for the purification of DNA methyltransferase activity from human placenta. The procedure avoids the isolation of nuclei and the dialysis and chromatography of large volumes. A purification of 38,000-fold from the whole cell extract has been achieved. The procedure employs ion exchange, affinity, and hydrophobic interaction chromatography coupled with preparative glycerol gradient centrifugation. A protein of 126,000 daltons was found to copurify with the activity and was the major band seen in the most highly purified material after SDS gel electrophoresis. This observation, coupled with an observed sedimentation coefficient of 6.3S, suggests that the enzyme is composed of a single polypeptide chain of this molecular weight. Hemimethylated DNA was found to be the preferred substrate for the enzyme at each stage in the purification. The ratio of the activity of the purified product on hemimethylated to that on unmethylated M13 duplex DNA was about 12 to 1. Thus, the purified activity has the properties postulated for a maintenance methyltransferase. The availability of highly purified human DNA methyltransferase should facilitate many studies on the structure, function, and expression of these activities in both normal and transformed cells.

Adsorption↗

Estradiol-induced LH release in juvenile female rats: nembutal blocks both the decline and the exposure of nonavailable pituitary LHRH receptor sites.

We have previously shown that, as seen in the adult rat, pituitary LHRH receptor content declines during the hours encompassing the first preovulatory LH surge. This decrease in receptor number was prevented, however, when pituitary membranes were treated with MgCl2 to dissociate endogenously bound ligand(s). The present study investigates: whether the first proestrous reduction in available LHRH receptors can be reversed by subjecting the pituitary membranes to a less drastic, dilution-washing procedure previously reported to be highly effective in dissociating bound LHRH, and whether Nembutal blockade of the proestrous decline in LHRH receptors also prevents the dissociation-induced exposure of additional LHRH binding sites. A premature LH surge was induced by exposing juvenile female rats to proestrous-type levels of plasma estradiol (E2) via Silastic capsules. A decline in available LHRH receptors was found around the time of this steroid-induced LH surge. A marked increase in receptor number was, however, observed upon dilution-washing of the membranes. The increase in receptor number was not accompanied by any changes in receptor affinity (ka). Nembutal administration blocked both the LH surge and the decline in available LHRH receptors. Moreover, dilution-washing of pituitary membranes from Nembutal-treated rats failed to uncover additional LHRH binding sites. The results suggest that a significant portion of the proestrous decline in pituitary LHRH receptors is due to a reduced availability of the receptor to binding. Whether such a phenomenon is due to true occupancy by endogenous ligand(s) or to binding-dependent localization of the receptor within the cell membrane is unclear.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Quantification of lumbar function. Part 2: Sagittal plane trunk strength in chronic low-back pain patients.

A prototype sagittal plane trunk strength tester was used to measure trunk strength in 286 chronic low-back pain patients. Initial data for this patient group are compared with data acquired previously from a group of controls, adjusted for age, sex, and body weight. Distinct patterns characterize the patient sample as opposed to the controls: Patient values for both flexors and extensors were markedly decreased, with greater variability; Extensor strength was affected more significantly than flexor strength; Discrepancies between patients and controls were greater for females than for males; High-speed dropoff ratios were much lower for patients, both in flexion and extension. These results demonstrate that strength deficits are a major factor in the deconditioning syndrome associated with chronic low-back pain.

Adult↗

Quantification of lumbar function. Part 3: Preliminary data on isokinetic torso rotation testing with myoelectric spectral analysis in normal and low-back pain subjects.

A prototype isokinetic torso rotation unit and an EMG signal processing system were utilized to obtain preliminary information on torso rotation. In Study 1, range-of-motion was found to be surprisingly uniform between low-back pain patients and normal subjects, although there was a significant strength variation between them at all isokinetic speeds tested. Both female patients and normal females showed approximately 70%-75% of the strength (torque/body weight) levels relative to their male counterparts. The decrement in trunk strength at high speeds was proportional for both patients and controls and was not nearly as dramatic as the decrement seen in the sagittal plane. In Studies 2 and 3, anatomic relationships evaluated by EMG testing of obliques and erector spinae showed that the contralateral abdominal obliques were the most consistent muscles providing a significant torsional moment to the spine.

Adult↗

Quantification of lumbar function. Part 1: Isometric and multispeed isokinetic trunk strength measures in sagittal and axial planes in normal subjects.

The goals of this study were to: evaluate the repeatability of a method of measuring trunk strength; measure isometric and isokinetic strength of trunk flexors, extensors and rotators; explore relationships among these muscle groups; and compare a torque to body weight adjustment measure versus lean body weight. One hundred twenty-five normal subjects (62 males, 63 females) were tested using a Cybex prototype trunk extension-flexion system. Sixty-seven subjects (25 males, 42 females) were tested using a prototype torso rotation unit. Fifty were tested on both devices. Results demonstrated that the strength data were reliable, with strength being greatest in extension. The following were also learned-torque output declined slightly with increased speed; extensor-flexor strength remained consistent from 18 to 44 years; extension-flexion ratios exceeded 1.1:1; left to right rotation ratios remained 1:1; there was no significant difference between torque adjusted to body weight or to lean body weight.

Adult↗

Structural organization of interspersed repetitive elements present in the DNA of Mus musculus.

Two-dimensional displays of the restriction fragments from the DNA of Mus musculus revealed a complex species-specific pattern produced from nonsatellite repetitive sequences. The patterns have been used as a guide in the direct purification of a group of broadly interspersed repeated DNA sequences (characterized by a 1350-bp Eco-Bam fragment) that have been studied by molecular cloning, restriction mapping and genomic Southern blotting. These studies show that the cloned representatives originate from an abundant group of sequences that share homology with about 2% of the mouse genome. The sequences do not appear to share homology with mouse-interspersed-family-1 (MIF-1) nor with the major AT-rich satellite sequences of mouse. They appear to be part of a group of larger repetitive elements that is both broadly interspersed and heavily methylated in normal mouse tissue.

Animals↗

Methylation of a middle repetitive DNA sequence class during differentiation in Friend erythroleukemia cells.

We have examined the methylation patterns within middle repetitive sequences in Friend erythroleukemia cells. Mouse-interspersed-family-1 (MIF-1) and a group characterized by a 1350-bp Eco-Bam fragment cloned into pBR322 as plasmid pFS-13, are both less modified in Friend cell DNA than in normal tissue DNA. The pattern of methylation present in pFS-13 homologous sequences was found to be stable during cell division, i.e., somatically inherited, and stable during differentiation induced by HMBA.

Acetamides↗

The tumorigenicity of 5-azacytidine in the male Fischer rat.

5-Azacytidine was administered to young adult male Fischer rats. Tumors were found in 31 out of 70 rats that had received 5-azacytidine and survived 18 months from the start of the experiment. Several rats had multiple primary tumors. In the rats that were tested for complete carcinogenicity a variety of tumor types was found. These included acute leukemia and malignant reticuloendotheliosis, and tumors of the testis, skin, and bronchus. No hepatic tumors were found in the group that was tested for hepatic tumor initiation. Hepatocellular carcinomas were found only in the group that was examined for hepatic tumor promotion by receiving a prior initiating dose of diethylnitrosamine. No tumors were found in the age controls. Thus, in these initial experiments, 5-azacytidine appeared to be a complete carcinogen, inducing tumors in several organs, and a tumor promoter but not a complete carcinogen for the liver.

Animals↗