Search PubMed⌕ Search

Biomedical subjects

S Franklin

Publications and source records attributed to S Franklin.

At least 37 records · Page 2Linked to original sources
PubMed1995

Mice deficient in IL-1 beta-converting enzyme are defective in production of mature IL-1 beta and resistant to endotoxic shock.

IL-1 beta-converting enzyme (ICE) cleaves pro-IL-1 beta to generate mature IL-1 beta. ICE is homologous to other proteins that have been implicated in apoptosis, including CED-3 and Nedd-2/lch-1. We generated ICE-deficient mice and observed that they are overtly normal but have a major defect in the production of mature IL-1 beta after stimulation with lipopolysaccharide. IL-1 alpha production is also impaired. ICE-deficient mice are resistant to endotoxic shock. Thymocytes and macrophages from the ICE-deficient animals undergo apoptosis normally. ICE therefore plays a dominant role in the generation of mature IL-1 beta, a previously unsuspected role in production of IL-1 alpha, but has no autonomous function in apoptosis.

Animals↗
PubMed1994

Crystal structure of the cysteine protease interleukin-1 beta-converting enzyme: a (p20/p10)2 homodimer.

Interleukin-1 beta-converting enzyme (ICE) proteolytically cleaves pro-IL-1 beta to its mature, active form. The crystal structure at 2.5 A resolution of a recombinant human ICE-tetrapeptide chloromethylketone complex reveals that the holoenzyme is a homodimer of catalytic domains, each of which contains a p20 and a p10 subunit. The spatial separation of the C-terminus of p20 and the N-terminus of p10 in each domain suggests two alternative pathways of assembly and activation in vivo. ICE is homologous to the C. elegans cell death gene product, CED-3, and these may represent a novel class of cytoplasmic cysteine proteases that are important in programmed cell death (apoptosis). Conservation among members of the ICE/CED-3 family of the amino acids that form the active site region of ICE supports the hypothesis that they share functional similarities.

Amino Acid Chloromethyl Ketones↗
PubMed1993

Essentialism, which essentialism? Some implications of reproductive and genetic techno-science.

New technologies, such as genetic screening, artificial insemination, in vitro fertilization, and pre-natal diagnosis, have given new meaning to human reproduction. Such innovations make clear that marriage, procreation, and the biological family are not the sole "natural" means of perpetuating the human race. One would have hoped that these inventions would eventually have raised in public regard the gay/lesbian family to the same level as heterosexuality and the biological family. Franklin shows, however, that the old heterosexual essentialism is preserved by government restricting the use of the new technologies to two-parent families consisting of both mother and father. What should have resulted in the erosion of heterosexual privilege has, instead, led to its reinforcement. Franklin draws a parallel with the AIDS epidemic which could have been the opportunity to spread knowledge and acceptance of varied forms of sexuality but has instead been used to shore up a traditional sexual morality and a renewed vilification of homosexuality.

Female↗
PubMed1992

The caregiver reaction assessment (CRA) for caregivers to persons with chronic physical and mental impairments.

The development and testing of a multidimensional instrument to assess the reactions of family members caring for elderly persons with physical impairments, Alzheimer's disease, and cancer is reported. Forty items were administered to a sample of 377 caregivers of persons with physical impairments and Alzheimer's disease. Five dimensions of caregivers' reactions were identified through exploratory factor analysis. Using confirmatory factor analysis on an independent sample (N = 377), these dimensions were tested for factorial invariance across spouse and nonspouse caregivers and between caregivers of persons with cancer and those caring for persons with Alzheimer's disease. The subscales also had a high level of factorial invariance across a three-wave panel study (N = 185). The subscales appeared consistent with first order tests of construct validity.

Aged↗
PubMed1992

Construction and expression of nonsense suppressor tRNAs which function in plant cells.

An Arabidopsis thaliana L. DNA containing the tRNA(TrpUGG) gene was isolated and altered to encode the amber suppressor tRNA(TrpUAG) or the ochre suppressor tRNA(TrpUAA). These DNAs were electroporated into carrot protoplasts and tRNA expression was demonstrated by the translational suppression of amber and ochre nonsense mutations in the chloramphenicol acetyltransferase (CAT) reporter gene. DNAs encoding tRNA(TrpUAG) and tRNA(TrpUAA) nonsense suppressor tRNAs caused suppression of their cognate nonsense codons in CAT mRNAs, with the tRNA(TrpUAG) gene exhibiting the greater suppression under optimal conditions for expression of CAT. The development of these translational suppressors which function in plant cells facilitates the study of plant tRNA gene expression and will make possible the manipulation of plant protein structure and function.

Anticodon↗
PubMed1992

Outcome of renal transplantation in children aged 1-5 and 6-18 years.

Results of renal transplantation in younger children have not been very encouraging in the past. We therefore studied the effect of newer immunosuppressive regimens on the outcome of renal transplantation of 5 children aged 2.9 +/- 1.3 years (range 1.6-5.0), and compared it to 10 children of an older pediatric patient group aged 11.4 +/- 4.4 years (range 6.0-18.5). All patients with the exception of 1 underwent dialysis. The percentage of cadaveric and live-related transplants was similar in both groups. Recipients of a cadaveric transplant had at least 3 blood transfusions; recipients of live-related transplants had donor-specific transfusions with azathioprine. Posttransplantation immunosuppression consisted of prednisone and azathioprine; recipients of cadaveric transplants received also ciclosporin. Rejection episodes and side effects (hypertension, hirsutism) were comparable in both groups. In the younger patient group, 1 patient died of a congenital lung abnormality but had a functioning graft. In the older patient group, 1 patient lost his graft 16 months posttransplantation due to reduction of his immunosuppressives, necessitated by a severe CMV infection. Growth and development improved in the younger patient group, but was stable in older patients. Renal transplantation is a suitable option in younger pediatric patients. Graft survival rates are comparable to those of older patients.

Adolescent↗
PubMed1991

Purification and biochemical characterization of recombinant simian immunodeficiency virus protease and comparison to human immunodeficiency virus type 1 protease.

Simian immunodeficiency virus protease (SIV-PR) was produced in Escherichia coli with a recombinant expression system in which the mature enzyme autoprocessed from a precursor form. Recombinant SIV and HIV-1 (human immunodeficiency virus, type 1) proteases were purified from bacterial cell lysates by use of sequential steps of ammonium sulfate precipitation and size-exclusion and ion-exchange chromatography. The amino acid composition, amino-terminal sequence, and molecular weight (monomer) of the recombinant SIV-PR were in accord with that of the 99 amino acid polypeptide predicted from the SIVMac-PR nucleotide sequence. The active form of SIV-PR was shown to be dimeric by gel filtration chromatography. Inhibition by pepstatin A, time-dependent inactivation by 1,2-epoxy-3-(4-nitrophenoxy)propane, and pH rate profiles using oligopeptide substrates demonstrated that SIV-PR behaves as an aspartic protease. Recombinant HIV-1 Pr55gag precursor was processed in vitro by SIV-PR and HIV-1 PR with indistinguishable proteolytic patterns upon NaDodSO4-polyacrylamide gel electrophoresis. Oligopeptide substrates for HIV-1 PR were found to be suitable substrates for recombinant SIV-PR with the exception of a peptide containing the site identified for p66/p51 cleavage (Phe*Tyr) within HIV-1 reverse transcriptase (RT). Several synthetic peptide analogue inhibitors of HIV-1 PR were also potent inhibitors of SIV-PR, indicating that SIV infection in macaques and rhesus monkeys should be useful models for the preclinical evaluation of acquired immunodeficiency syndrome (AIDS) therapeutics targeted towards the virally encoded HIV-1 protease.

Amino Acid Sequence↗
PubMed1991

Role of combination drug therapy with a class IC antiarrhythmic agent and mexiletine for ventricular tachycardia.

The combination of mexiletine and a class IC antiarrhythmic agent (encainide, propafenone or flecainide) was evaluated by electrophysiologic testing in 14 patients with a history of sustained ventricular tachycardia whose tachycardia remained inducible during therapy with the class IC drug alone. During the control drug-free state, all patients had inducible ventricular tachycardia, with a mean cycle length of 260 ms (range 190 to 400). During monotherapy with the IC agent the tachycardia remained inducible in each patient, but there was a significant increase in the cycle length to 340 ms (240 to 500) (p less than 0.001). The effective refractory period of the ventricle was not altered. Treatment with mexiletine (oral in 13 and intravenous in 1) was begun and electrophysiologic testing was repeated. Ventricular tachycardia in one patient was rendered noninducible and one patient had arrhythmia aggravation. The tachycardia in the remaining 12 patients remained inducible but its average cycle length increased further to 392 ms (340 to 460) (p = NS). Nine patients had rate slowing and the average cycle length of the ventricular tachycardia in this group was significantly increased (302 to 388 ms, p less than 0.05). The average effective refractory period was significantly increased during combination therapy (267 ms) compared with no drug therapy (235 ms) and therapy with the class IC drug alone (247 ms) (p less than 0.05). After a mean follow-up interval of 22 months, seven patients continue on the combined treatment and have no ventricular tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Neuropsychological studies of auditory-visual fusion illusions. Four case studies and their implications.

A heard speech sound which is not the same as the synchronized speech sound can sometimes give rise to an illusory phonological percept. Typically, a heard /ba/ combines with a seen /ga/ to give the impression that /da/ has been heard (McGurk, H. and MacDonald, J. Nature Lond. 264, 746-748, 1976). We report the susceptibility to this illusion of four individuals with localized brain lesions affecting perceptual function. We compare their performance to that of ten control subjects and relate these findings to the efficiency of processing seen and heard speech in separate and combined modalities. The pattern of performance strongly suggests LH specialization for the phonological integration of seen and heard speech. The putative site of such integration can be effectively isolated from unilateral and from bilateral inputs and may be driven by either modality.

Adult↗
PubMed1990

Prognosis in infiltrating lobular carcinoma. An analysis of "classical" and variant tumors.

A precise histologic and clinical delineation of infiltrating lobular carcinoma, including its variant forms, has been elusive. We studied 230 patients with stage I and II infiltrating lobular carcinoma treated by mastectomy and axillary lymph node dissection. Included were 176 patients with the "classical" or "Indian-file" pattern (IFL) of infiltrating lobular carcinoma, and 54 patients with variant (VAR) histology [solid (SOL), alveolar (ALV), and mixed (MIX) patterns]. IFL patients were younger than VAR patients (52 versus 57 years; p = 0.004), and IFL patients were more likely to be premenopausal (p = 0.013). Microscopic multifocality and intraepithelial ductular extension of LCIS were both more frequent in the IFL group (p = 0.008 and 0.03, respectively). There was no significant difference in tumor size (T1 versus T2), axillary lymph node status, or TNM stage at presentation. Median survival time and time to recurrence was similar in the two groups. Although it was not statistically significant, median survival for stage I and low-axillary lymph node positive stage II IFL patients was better than that of VAR patients. One hundred forty of our 176 IFL patients (80%) could be matched with infiltrating duct carcinoma (IFDC) patients of similar age at diagnosis, menstrual status, tumor size, and axillary lymph node involvement. When stratified by stage, stage I IFL patients had a significantly higher disease-free survival (p = 0.02) than comparable patients with IFDC. There was not a significant difference in disease-free survival when stage II IFL and IFDC patients were compared. The unmodified term "infiltrating lobular carcinoma" should be restricted to lesions exhibiting the classical or Indian-file (IFL) microscopic architectural pattern in approximately 85% of the tumor. Patients with VAR forms of IFL may have a less favorable prognosis and should be distinguished from those with classical IFL for further characterization.

Breast Neoplasms↗
PubMed1989

The evolution of a simplified method for interpretation of EEG in the preterm neonate.

We describe the evolution of a simplified method for the interpretation of serial EEG in preterm neonates which was tested in a first sample and revised and improved in a second sample of preterm neonates. There were 185 EEGs in the first sample and 206 EEGs in the second sample. The interpretation of the EEGs was related to mental, motor and neurological outcome in late infancy. Serial EEG is an excellent indicator of brain function in the preterm neonate.

Brain↗
PubMed1989

Development of a confirmatory enzyme-linked immunosorbent assay for HIV-1 antibodies.

We subcloned six discrete protein-coding regions representing the gag (Kp24 and Kp55), env (Kp41, Kp120N, and Kp120CC), and pol (Kp66/31) gene products of the human immunodeficiency virus type 1 (HIV-1) and expressed them in Escherichia coli as fusion proteins with the first 56 residues of galactokinase. An enzyme-linked immunosorbent assay for confirming the presence of HIV-1 antibodies was developed by coating the six purified antigens on individual wells of a microtiter plate (the HIVAGEN assay). This assay yielded no false-negative results and fewer indeterminate results than the Western blot assay for 143 specimens from patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). Analysis of 1016 specimens from seronegative donors by the HIVAGEN assay yielded no false-positive results, and the rate of indeterminate results was substantially lower than for the Western blot assay. The HIVAGEN assay is well suited for routine confirmation of the presence of HIV-1 antibodies because it is objective, quantitative, rapid, precise, and readily automatable.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Targeted antagonism of galactosamine toxicity in normal rat hepatocytes in vitro.

We present evidence that normal hepatocytes can be specifically protected from galactosamine toxicity in vitro by targeting an antagonist to these cells via receptor-mediated endocytosis. The strategy is based upon the following principles: 1) galactosamine is a highly selective hepatotoxin that causes a dose-dependent depletion of uridine intermediates; 2) galactosamine toxicity can be antagonized by supplemental administration of uridine; 3) normal hepatocytes possess unique cell-surface receptors that can internalize galactose terminal (asialo-)glycoproteins with subsequent degradation of the glycoprotein ligand. Based on these facts, we hypothesized that chemical coupling of a galactosamine antagonist to an asialoglycoprotein could result in cell-specific delivery and protection of normal hepatocytes by targeting the antagonist via asialoglycoprotein receptors. Using a model system consisting of freshly isolated rat hepatocytes (receptor (+)) and Morris 7777 rat hepatoma (receptor (-)) cells, sensitivity to galactosamine in vitro was determined and found to be similar for both types of cells. A targetable antagonist was synthesized by coupling uridine monophosphate to asialoorosomucoid in a molar ratio of 5 to 1. Exposure of Morris 7777 cells to the targetable antagonist in the presence of a toxic concentration of galactosamine did not protect these cells as evidenced by a steady decline in the number of viable cells in a fashion identical to cells treated with galactosamine alone. However, normal hepatocytes that received the conjugate in the presence of galactosamine were protected as their viable cell number remained the same as control (untreated) cells. Competition by an excess of asialoglycoprotein inhibited the protective effect of the conjugate, supporting the concept that the asialoglycoprotein component of the conjugate was responsible for the specific delivery of the antagonist to the target cells.

Animals↗
PubMed1988

High hydrostatic pressure effects in vivo: changes in cell morphology, microtubule assembly, and actin organization.

We present the first study of the changes in the assembly and organization of actin filaments and microtubules that occur in epithelial cells subjected to the hydrostatic pressures of the deep sea. Interphase BSC-1 epithelial cells were pressurized at physiological temperature and fixed while under pressure. Changes in cell morphology and cytoskeletal organization were followed over a range of pressures from 1 to 610 atm. At atmospheric pressure, cells were flat and well attached. Exposure of cells to pressures of 290 atm or greater caused cell rounding and retraction from the substrate. This response became more pronounced with increased pressure, but the degree of response varied within the cell population in the pressure range of 290-400 atm. Microtubule assembly was not noticeably affected by pressures up to 290 atm, but by 320 atm, few microtubules remained. Most actin stress fibers completely disappeared by 290 atm. High pressure did not simply induce the overall depolymerization of actin filaments for, concurrent with cell rounding, the number of visible microvilli present on the cell surface increased dramatically. These effects of high pressure were reversible. Cells re-established their typical morphology, microtubule arrays appeared normal, and stress fibers reformed after approximately 1 hour at atmospheric pressure. High pressure may disrupt the normal assembly of microtubules and actin filaments by affecting the cellular regulatory mechanisms that control cytological changes during the transition from interphase into mitosis.

Actins↗
PubMed1988

DHFR coamplification of t-PA in DHFR+ bovine endothelial cells: in vitro characterization of the purified serine protease.

High-level expression of human tissue-type plasminogen activator was accomplished in endothelial cells by a novel approach to dihydrofolate reductase (DHFR) coamplification in DHFR+ cells. A tripartite mammalian expression vector coding for DHFR, neomycin phosphotransferase, and the t-PA gene was introduced into bovine endothelial cells by transfection and selection for G418 resistance. Upon methotrexate selection of these transformants, we obtained endothelial cells that had amplified the plasmid-encoded DHFR and t-PA genes. As a result, cell lines were isolated that efficiently produced t-PA (greater than 4 pg/cell.day). This t-PA was purified and compared with recombinant t-PA produced in Chinese hamster ovary cells. These two t-PA samples differed in carbohydrate composition, and amounts of 530 and 527 amino acid forms but had similar in vitro activity.

Animals↗
PubMed1988

Adrenal enkephalin biosynthesis regulated by glucocorticoid.

Denervation of the rat adrenal results in a 10 to 20-fold increase in enkephalin-containing EC peptides 4 days after surgery. This denervation-induced rise in medullary EC peptides is blocked by hypophysectomy (hypox) and partially reinstated by dexamethasone or ACTH treatment. Culture of adrenal medullary explants (glands) for 4 days in serum-free medium without dexamethasone resulted in a 6-fold increase in EC peptides in glands from hypox rats while the addition of dexamethasone (10-5M) produced a 29 fold increase. These results indicate that a loss of depolarizing stimuli produced by denervation in vivo or explanation in vitro initiates a pretranslational event which requires glucocorticoid for the full expression of EC peptide biosynthesis.

Adrenal Medulla↗