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Biomedical subjects

R Schultz

Publications and source records attributed to R Schultz.

At least 109 records · Page 6Linked to original sources

Establishment and characterization of a cell line derived from a spontaneous murine lung carcinoma (M109).

The Madison lung (M109) tumor cell line, initiated from a "spontaneous", anaplastic murine lung carcinoma, has been propagated continuously in vitro for more than 300 cell generations. Cytogenetic analysis revealed a mouse karyotype with a mode of 78 chromosomes (2n = 40). Three distinct marker chromosomes were identified by trypsin-giemsa banding. The cells piled up in culture and had a short generation time and high plating efficiency. Electron microscopy revealed highly undifferentiated cells with little rough endoplasmic reticulum, an abundance of free polysomes, the presence of few and often odd-shaped mitochondria, lipid bodies and phagocytic vacuoles. Virus particles of the C-type were found frequently. The subcutaneous transplantation of M109 cultured cells at a relatively low cell inoculum produced highly metastatic tumors in syngeneic BALG/c mice.

Adenocarcinoma, Bronchiolo-Alveolar↗

Dependence liability of enkephalin in the myenteric plexus of the guinea pig.

The endogenous ligands of opiate receptors, methionine-eukephalin and leucine-enkephalin, were tested for their ability to maintain or to reinduce dependence in myenteric plexus-longitudinal muscle strips taken from tolerant/dependent guinea pigs. Both peptides fully substituted for the function morphine exerts in this preparation. It is concluded that the enkephalins posses a high degree of dependence liability.

Animals↗

Mode of stimulation by adenosine 3':5'-cyclic monophosphate of the sodium efflux in barnacle muscle fibres.

1. Giant fibres of the barnacle Balanus nubilus have been used as a preparation for studying the mode of action of cAMP on sodium transport. 2. It is shown that a concentration of cAMP as low as 10(-6)M, when micro-injected, causes a sharp rise in the radio-Na efflux. Ouabain fails to reverse the cAMP effect. 3. The magnitude of the response of the Na efflux to cAMP is markedly reduced by pre-injecting 100 or 500 mM-EGTA solutions or by omitting Ca2+ from the bathing medium. Both together fail to bring about a greater reduction in the response. 4. The response to cAMP is greatly reduced by pre-injecting the protein inhibitor of Walsh and practically abolished by pre-injecting 500 mM-EGTA and soaking in Ca-free artificial sea water, ASW. 5. The Ca2+-independent component of the Na efflux which is also stimulated by cAMP is shown to involve Na for H exchange. The magnitude of this exchange is governed by external pH. 6. The Na efflux into Ca2+-free, Li+-ASW is shown to be markedly stimulated by injecting cAMP, an effect which is enhanced by reducing external pH. 7. The Na efflux at 0 degrees C is stimulated by injecting cAMP. This is shown to be related to activation of the protein kinase by cAMP and to depend on the presence of external Ca2+. 8 (i) Ethacrynic acid when injected reduces the ouabain-insensitive Na efflux into HEPES-Ca2+-free ASW at pH 6-3. These same fibres show a marked response to cAMP. (II) The ouabain-insensitive Na efflux into HCO3-, Ca2+-free ASW from fibres pre-treated with ethacrynic acid fails to respond to external acidification. This is interpreted as indicating that ethacrynic acid inactivates the CO2-sensitive adenyl cyclase system. These same fibres when injected with cAMP show a marked response. (iii) Stimulation of the ouabain-insensitive Na efflux into HCO-3, Ca2+-free ASW by external acidification is reversed by injecting ethacrynic acid. These fibres when injected with cAMP show a reduced response. 9. It is concluded that: (i) stimulation of the Na efflux by injected cAMP is mainly due to activation of cAMP-dependent protein kinase; (ii) the underlying exchange mechanism consists of Na:Ca and Na:H exchange. Interaction of Ca2+ with a phosphorylated membrane, thereby modifying permeability remains as a real possibility; (iii) the site of action of CO2 and ethacrynic acid is the adenyl cyclase system. 10. The implications of activation of the adenyl cyclase system by CO2 and Na:H exchange are briefly touched upon.

Animals↗

Pharmacokinetics of gentamicin and kanamycin during hemodialysis.

The pharmacokinetics of gentamicin, kanamycin, and creatinine were studied in patients undergoing hemodialysis. After intravenous injection of single doses of the drugs, 50 to 60% of the doses of both antibiotics were cleared from the body during a 6-h period; this occurred almost entirely by the hemodialysis process. No correlation was found between the dialysance of the aminoglycosides and creatinine. The pharmacokinetic data were used to make dosage regimen recommendations for treatment of hemodialysis patients with these antibiotics.

Adult↗

Determinants of well-being in primary caregivers of spinal cord injured persons.

A study of well-being in middle-aged and elderly spinal cord injured persons (Decker & Schulz, 1985) found that long-term coping was facilitated by the presence of a primary support person or caregiver. The purpose of this study was to identify the determinants of life satisfaction and depression in 67 primary caregivers of middle-aged and elderly spinal cord injured persons. The study revealed that the availability of social support and feelings of control over one's life were important determinants of caregivers' well-being. In addition, those caregivers spending more time each day assisting the disabled person and feeling burdened by these responsibilities experienced more depression and less life satisfaction. In working with spinal cord injured persons, rehabilitation nurses must consider the well-being of the spinal cord injured person/primary caregiver dyad as an important focus of nursing assessment and intervention.

Aged↗

Cyclin-dependent kinases: initial approaches to exploit a novel therapeutic target.

Cyclin-dependent kinases (CDKs) have been recognized as key regulators of cell cycle progression. Alteration and deregulation of CDK activity are pathogenic hallmarks of neoplasia. Therefore, inhibitors or modulators would be of interest to explore as novel therapeutic agents in cancer, as well as other hyperproliferative disorders. Flavopiridol is a semisynthetic flavonoid that emerged from an empirical screening program as a potent antiproliferative agent that mechanistic studies demonstrated to directly inhibit CDKs 1, 2, and 4 as a competitive ATP site antagonist. Initial clinical trials have shown that concentrations that inhibit cell proliferation and CDK activity in vitro can be safely achieved in humans, and additional clinical trials will establish its clinical potential. To address the need for additional chemotypes that may serve as lead structures for drugs that would not have the toxicities associated with flavopiridol, compounds with a similar pattern of cell growth inhibitory activity in the National Cancer Institute's in vitro anticancer drug screen have been recognized by the computer-assisted pattern recognition algorithm COMPARE and then screened for anti-CDK activity in a biochemical screen. The benzodiazepine derivative NSC 664704 (7,12-dihydro-indolo[3,2-d][1]benzazepin-6(5H)-one) was revealed by that approach as a moderately potent (IC50 0.4 microM) inhibitor of CDK2, which in initial experiments shows evidence of causing cell cycle redistribution in living cells. NSC 664704 is, therefore, a candidate for further structural optimization, guided in part by understanding of the ATP-binding site in CDK2. This approach represents one way of combining empirical screening information with structure-based design to derive novel candidate therapeutic agents directed against an important cellular target.

Animals↗

Intrathecal low-dose bupivacaine versus lidocaine for in vitro fertilization procedures.

BACKGROUND AND OBJECTIVES: Recent controversy with the use of intrathecal lidocaine has prompted the search for suitable ambulatory surgery alternatives. The purpose of our study was to evaluate the clinical utility of intrathecal low-dose bupivacaine for outpatient transvaginal oocyte retrieval. METHODS: Forty women enrolled and completed our prospective, randomized, double-blinded study of intrathecal hyperbaric bupivacaine 3.75 mg (0.5 mL of 0.75%) with fentanyl 25 microg versus hyperbaric lidocaine 30 mg (2.0 mL of 1.5%) with fentanyl 25 microg. Onset and level of sensory and motor block; time to ambulation, urination, and discharge; and intra- and postoperative complications (hypotension, pruritus, nausea, emesis, postdural puncture headache, post spinal pain syndrome [PSPS]) were recorded. Data were evaluated using analysis of variance, chi-squared, and Mann-Whitney U tests, with P <.05 considered significant. RESULTS: In demographically similar groups, no differences were noted in times to onset and recovery of sensory and motor function, or complications; however, times to voiding and discharge were significantly longer in the bupivacaine group. Four and 2 patients in the bupivacaine and lidocaine groups, respectively, required intravenous analgesic supplementation. One patient in the lidocaine group experienced PSPS. CONCLUSIONS: Although prolongation to voiding and discharge was observed, intrathecal hyperbaric bupivacaine 3.75 mg with fentanyl 25 microg is a viable anesthetic for oocyte retrieval.

Adjuvants, Anesthesia↗

Telomerase inhibitors--oligonucleotide phosphoramidates as potential therapeutic agents.

We have designed, synthesized, and evaluated using physical, chemical and biochemical assays various oligonucleotide N3'-->P5' phosphoramidates, as potential telomerase inhibitors. Among the prepared compounds were 2'-deoxy, 2'-hydroxy, 2'-methoxy, 2'-ribo-fluoro, and 2'-arabino-fluoro oligonucleotide phosphoramidates, as well as novel N3'-->P5' thio-phosphoramidates. The compounds demonstrated sequence specific and dose dependent activity with IC50 values in the sub-nM to pM concentration range.

Amides↗

[Congenital infection due to herpes simplex virus].

Five cases of probably intrauterine herpesvirus infection are discussed. Four of them had clinical evidence of neonatal herpes, which was disseminated in two patients, localized to skin in one case and with SNC compromised in other. Natal or post natal infections were not considered to be possible in these infants due to the presence of symptoms in the first 24 hours of life, which made ascending transcervical or transplacental the most probable route for viral transmission. All cases were treated with a ten days course of intravenous acyclovir during 10 days. There of them had satisfactory evolution and the other two died at 9 days and at 2 months of life.

Acyclovir↗