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Biomedical subjects

J S Peterson

Publications and source records attributed to J S Peterson.

At least 19 recordsLinked to original sources

Stage-specific regulation of caspase activity in drosophila oogenesis.

In Drosophila oogenesis, the programmed cell death of germline cells occurs predominantly at three distinct stages. These cell deaths are subject to distinct regulatory controls, as cell death during early and midoogenesis is stress-induced, whereas the cell death of nurse cells in late oogenesis is developmentally regulated. In this report, we show that the effector caspase Drice is activated during cell death in both mid- and late oogenesis, but that the level and localization of activity differ depending on the stage. Active Drice formed localized aggregates during nurse cell death in late oogenesis; however, active Drice was found more ubiquitously and at a higher level during germline cell death in midoogenesis. Because Drice activity was limited in late oogenesis, we examined whether another effector caspase, Dcp-1, could drive the unique morphological events that occur normally in late oogenesis. We found that premature activation of the effector caspase, Dcp-1, resulted in a disappearance of filamentous actin, rather than the formation of actin bundles, suggesting that Dcp-1 activity must also be restrained in late oogenesis. Overexpression of the caspase inhibitor DIAP1 suppressed cell death induced by Dcp-1 but had no effect on cell death during late oogenesis. This limited caspase activation in dying nurse cells may prevent destruction of the nurse cell cytoskeleton and the connected oocyte.

Actins↗

Drosophila bunched integrates opposing DPP and EGF signals to set the operculum boundary.

The Drosophila BMP homolog DPP can function as a morphogen, inducing multiple cell fates across a developmental field. However, it is unknown how graded levels of extracellular DPP are interpreted to organize a sharp boundary between different fates. Here we show that opposing DPP and EGF signals set the boundary for an ovarian follicle cell fate. First, DPP regulates gene expression in the follicle cells that will create the operculum of the eggshell. DPP induces expression of the enhancer trap reporter A359 and represses expression of bunched, which encodes a protein similar to the mammalian transcription factor TSC-22. Second, DPP signaling indirectly regulates A359 expression in these cells by downregulating expression of bunched. Reduced bunched function restores A359 expression in cells that lack the Smad protein MAD; ectopic expression of BUNCHED suppresses A359 expression in this region. Importantly, reduction of bunched function leads to an expansion of the operculum and loss of the collar at its boundary. Third, EGF signaling upregulates expression of bunched. We previously demonstrated that the bunched expression pattern requires the EGF receptor ligand GURKEN. Here we show that activated EGF receptor is sufficient to induce ectopic bunched expression. Thus, the balance of DPP and EGF signals sets the boundary of bunched expression. We propose that the juxtaposition of cells with high and low BUNCHED activity organizes a sharp boundary for the operculum fate.

Amino Acid Sequence↗

Comparison of health outcomes among older construction and blue-collar employees in the United States.

Using the Health and Retirement Study, we compare the health outcomes of older male construction workers with their counterparts in other occupations. We find that construction workers are more susceptible to musculoskeletal problems, chronic lung disease, and emotional/psychiatric disorders. Older construction workers were 1.4 times more likely to have a back problem and 1.3 times more likely to have a foot or leg problem than were other blue-collar workers. Nonsmoking older construction workers were 3.2 times more likely to have chronic lung disease than their nonsmoking blue-collar counterparts. When accounting for alcohol consumption, older construction workers were 1.7 times more likely to have been diagnosed with an emotional problem than other older blue-collar workers. The high rate of chronic lung disease is most likely related to on-the-job dust exposure, while the increased risk of emotional disorders might be due to the dynamics of the construction labor market.

Alcohol Drinking↗

Mini-pig urinary bladder function: comparisons of in vitro anticholinergic responses and in vivo cystometry with drugs indicated for urinary incontinence.

1. Studies of carbachol-induced contractions on mini-pig bladder tissue strips in vitro demonstrated that antagonist drugs produced a rank order of potency similar to that observed in guinea-pig tissues: propantheline approximately atropine greater than oxybutynin greater than dicyclomine greater than HHSiD greater than imipramine greater than terodiline approximately AF-DX 116. The drugs appeared to show competitive antagonism and the tissues exhibited resistance to complete cholinergic blockade. 2. Cytometry performed in vivo on awake mini-pigs also showed that i.v. cholinergic antagonists produced a dose-dependent depression of peak intravesical bladder pressure (PvesP) during slow filling of the bladder using urethral catheters, with a rank order of potency: atropine greater than oxybutynin approximately propantheline greater than HHSiD approximately dicyclomine greater than terodiline. Other parameters of the cystometrogram were unaffected by the antagonists, except for residual volume, which generally increased after drug treatment. 3. Hexahydrosiladifenidol (HHSiD), an ileal-selective competitive muscarinic antagonist, was about as effective an antagonist as the clinically useful drugs oxybutynin or dicyclomine, both in vitro and in vivo, suggesting that HHSiD may have useful therapeutic effects for the treatment of urinary incontinence. 4. Correlation of the rank order of potency for muscarinic antagonism between mini-pigs and guinea-pigs was very high in vitro (r = 0.97, P less than 0.05), as was the correlation among the drugs for their ability to depress PvesP of the cystometrogram in vivo (r = 0.89, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Smokeless tobacco: a product for the new generation of tobacco users. Dipping and chewing in the Northwest Territories, Canada, and its global relevance.

The use of smokeless tobacco appears to be a socially acceptable behavior among certain ethnic and cultural groups in developing and developed countries. Some native groups in the Northwest Territories have traditionally used smokeless tobacco. With the visits of the merchant supply ships to the Northwest Territories in the early 1950's, a wider commercial variety of smokeless tobacco began to be used. Of great concern is the generation of Canadian children and adolescents who start this habit and become addicted to smokeless tobacco during their primary and secondary school years. Smokeless tobacco is reemerging as a popular form of tobacco among children and adolescents in Canada, the United States (including Alaska), Scandinavia and Britain. Chemical analysis of samples of smokeless tobacco from six countries has revealed that moist snuff obtained in 1985, from Gjoa Haven, Northwest Territories (imported from the United States) had the highest levels of cancer causing tobacco-specific nitrosamines (TSNA) of 228,400 and 240,100 parts per billion. If these levels were found in any other consumer product today, it would be banned from the marketplace. Because of their known carcinogenicity, the United States Department of Agriculture and Federal Food and Drug Administration have set up strict tolerance levels for human exposure to these chemicals and they prohibit the sale of beer, bacon or baby bottle nipples that contain levels greater than 10 parts per billion. TSNA concentrations in snuff exceed the levels of nitrosamines in other consumer products by over one hundredfold. During snuff dipping or chewing tobacco, the nitrosation process continues within the mouth.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

In vivo cystometrogram studies in urethane-anesthetized and conscious guinea pigs.

Urinary bladder cystometry using urethral catheters is described in vivo in a urethane-anesthetized guinea pig preparation and compared to an awake-animal preparation in which surgically implanted catheters were used. Anticholinergic drugs dose-dependently inhibited the peak intravesical pressure (PvesP) to a maximum of approximately 80% but had no effect on other cystometrogram (CMG) parameters (threshold pressure, bladder capacity). Stereoselectivity was evident; dexetimide but not levetimide potently depressed PvesP. Oxybutynin was equipotent (ID50 approximately 0.15 mg/kg) in both preparations and showed a similar duration of action (t1/2 = 48-53 min). The data suggests that CMG parameters and the effects of oxybutynin were not affected by urethane anesthesia, making the in vivo urethane-anesthetized guinea pig preparation a valuable tool to evaluate both the filling and voiding phases of cystometry.

Anesthesia↗

Effects of selective cholinergic antagonists and alpha,beta-methylene ATP on guinea-pig urinary bladder contractions in vivo following pelvic nerve stimulation.

1. An in vivo preparation measuring functional detrusor muscle strength in terms of intravesical bladder pressure (Pves) following in situ pelvic nerve stimulation has been developed in urethane-anaesthetized guinea pigs. 2. The increase in bladder pressure following pelvic nerve stimulation was abolished by topical lidocaine or tetrodotoxin, suggesting a neurogenic origin for the in vivo contractile response. 3. Cholinergic antagonists (i.v.) decreased the amplitude of the peak pressure response by about 50% at both high (30 Hz) and low (5 Hz) stimulation rates, with a rank order of potency of atropine greater than propantheline greater than oxybutynin greater than hexahydrosiladifenidol greater than pirenzepine greater than methoctramine. 4. The P2 purine receptor antagonist, alpha,beta-methylene ATP (i.v.), antagonized pelvic nerve-stimulated bladder contractions differentially at 5 and 30 Hz. At low frequencies, alpha, beta-methylene ATP was both more potent (2.5-fold) and more efficacious (-77 compared to -55% delta) than at 30 Hz. Atropine and alpha,beta-methylene ATP together completely inhibited the contractile response. 5. Together, the findings indicate that in guinea pigs, urinary bladder contractions induced by pelvic nerve stimulation in vivo may be mediated by both muscarinic and purinergic receptors and that these bladder contractions may be mediated by the M2 beta subtype rather than by M1 or M2 alpha muscarinic receptors.

Adenosine Triphosphate↗

The anticholinergic activity of agents indicated for urinary incontinence is an important property for effective control of bladder dysfunction.

The anticholinergic, antispasmodic and local anesthetic properties of agents indicated for the treatment of neurogenic bladder disorders were compared with known reference drugs in vitro and in cystometric studies in vivo in the guinea pig. Highly significant correlations (P = .0001) were found among the potencies of drugs to inhibit carbachol-induced isolated guinea pig detrusor muscle contraction in vitro and peak intravesical bladder pressure in vivo in the guinea pig cystometrogram, a test that provides the integrated micturition response in the intact animal. In contrast, there was no significant correlation (P greater than .5) among the potencies of the drugs to depress bladder contractile responses (in vitro and in vivo in the cystometrogram) and their potencies as antispasmodic or local anesthetic agents. Based on these correlations, we suggest that the anticholinergic component of the drugs' action is important in current effective therapies of bladder dysfunction. However, the possibility that other ancillary activities may also contribute to the specific mechanism of action of these agents in the urinary bladder is not ruled out.

Anesthetics, Local↗

R and S enantiomers of oxybutynin: pharmacological effects in guinea pig bladder and intestine.

Oxybutynin (Ditropan) is widely utilized in treatment of incontinence due to neurogenic bladder dysfunction. We prepared its R and S enantiomers and evaluated their antimuscarinic, Ca++-channel antagonistic and spasmolytic effects in guinea pig detrusor strips and ileal longitudinal muscle. Ussing chambers were used to assess inhibition of carbachol-induced mucosal Cl-secretion in vitro. The enantiomers and the racemate were also tested in in vivo preparations for local anesthetic activity and for antimuscarinic activity in the slow filling cystometrogram. Stereoselective antimuscarinic effects [R)OXY:(R/S)OXY:(S)OXY) were evident for isolated ileal longitudinal (0.12:1.0:4.5) and bladder detrusor muscle (0.5:1.0:13) isolated ileal mucosa (0.2:1:8.9) and acetylcholine stimulated phosphoinositide turn-over in vitro (0.24:1.0:39). Stereoselectivity was also evident for the volume-induced contractions of the cystometrogram in vivo (0.7:1:15). In contrast, no stereoselectivity was observed for Ca++-channel antagonism, spasmolytic and local anesthetic properties of (R/S)OXY and its enantiomers.

Anesthetics, Local↗

Ocular hypertensive responses in pigmented rabbits following different methods of waterloading.

Waterloading tests are used in rabbits to screen potentially useful ocular hypotensive drugs. The present study examines the ocular hypertensive response following oral, intravenous and intraperitoneal administration of water in conscious Dutch belt pigmented rabbits. All methods of waterloading were well tolerated by rabbits. However, intraperitoneal waterloading provided an ocular hypertensive effect of longer duration than either oral or intravenous waterloading.

Animals↗

An investigation of Jellinek's phases as they apply to both men and women.

Data comparing the symptom progressions reported by a group of 115 male alcoholics and 41 female alcoholics were correlated with the symptom progression described by Jellinek in 1952. Correlations were obtained for the phase marker symptoms, the phase markers and their phases, and for the overall progression. Results did not support Jellinek's model for the phase markers as reported by the men and by the entire group. Women, however, were shown to correlate perfectly with the phase markers as described by Jellinek. Significant correlations were obtained for the phase markers and their phases, and for the overall progression. Even though the correlations were significant, their values were not very great and this was taken as an indication of only modest support for Jellinek's symptom progression.

Alcoholism↗

Anterior subcapsular cataracts: a review of potential etiologies.

Photographs of amiodarone-induced anterior subcapsular lens opacities and axial punctate lens opacities are presented and compared for the first time. The similarities and differences between these lens opacities and phenothiazine-induced lens opacities are discussed. Potential etiologies for anterior subcapsular cataracts are reviewed. The biomicroscopic techniques required to appreciate subtle lens opacities are mentioned. The importance of recognizing and recording subtle lens opacities is discussed.

Adult↗

Amiodarone keratopathy and lens opacities.

Amiodarone hydrochloride is an antiarrhythmic drug which produces a keratopathy and anterior subcapsular lens opacities that are usually asymptomatic. Serial observations for eye findings were made in 21 patients on a daily dosage of 200-600 mg for periods ranging from six months to three years. Corneal deposits developed in all 21 patients and anterior lens opacities developed in 12 of 20 phakic patients. Resolving keratopathy was present in three patients for periods of at least seven to 20 months after amiodarone was discontinued.

Adult↗

Local ocular hypotensive effect of topically applied acetazolamide.

Acetazolamide's usefulness in the treatment of the glaucomas is limited by the systemic side effects that often accompany its oral administration, and topical administration was initially thought to have no effect upon the intraocular pressures of human and rabbit eyes. Recent studies, however, have shown the usefulness of water-loading tests for screening drugs with potential antiglaucomatous activity. We found evidence that topical acetazolamide has the ability to lessen the increase in intraocular pressure after water-loading in pigmented rabbits and correlated this observation with low levels (0.0 to 0.7 microgram/ml) of plasma acetazolamide. Further, a separate study showed that 10% topical acetazolamide can enhance the ocular hypotensive effects of systemically administered acetazolamide in normal pigmented rabbits, suggesting that topically applied acetazolamide can have a local effect on intraocular pressure.

Acetazolamide↗