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Biomedical subjects

J Frankel

Publications and source records attributed to J Frankel.

At least 19 recordsLinked to original sources
PubMed2001

A witness breaks his silence: the meaning of a therapist's response to an adolescent's self-destruction.

I describe the case of a self-mutilating adolescent girl and my dilemma, as her therapist, about telling her parents about her self-abuse. I use two complementary, mutually enhancing relational theories of trauma--Ferenczi's (1933) and Davies and Frawley's (1994)--to help understand the minefield I was in. Davies and Frawley describe certain relational configurations that are typical of trauma victims. I believe that it is not only unavoidable but therapeutically vital for therapists to participate in these configurations so they can know the patient's experience in a personal way. It is also crucial that they be witnesses who provide recognition for the patient's pain and, in so doing, relieve the intolerable feeling of isolation that Ferenczi proposed was the most basic trauma. In addition, I discuss the observation that some people who have not been previously traumatized in any gross way manifest characteristics of trauma.

Adolescent↗
PubMed2001

Anti-Yo antibody-positive cerebellar degeneration associated with endometrial carcinoma: case report and review of the literature.

Paraneoplastic cerebellar degeneration (PCD) is a rare, severely debilitating disease, often with a rapid onset and progression, which predate the diagnosis of malignancy. Despite characteristic features, diagnosis is commonly difficult and successful therapy, which relies on early instigation of treatment, is rare. Here we present a patient in whom anti-Yo antibody-positive PCD was associated with endometrial carcinoma and an extensive review of the literature outlining the clinical features, pathogenesis and treatment of PCD.

Aged↗
PubMed1999

Cellular events and the pattern of p53 protein expression following cyclophosphamide-initiated cell death in various organs of developing embryo.

This study was aimed at characterizing the temporal patterns of cell responses and p53 protein expression in the limbs, head, and liver of embryos responding to cyclophosphamide (CP)-induced teratogenic insult. ICR murine embryos were examined 24, 48, or 72 h after injection of 40 mg/kg CP on day 12 of pregnancy. The cellular events and temporal pattern of p53 protein expression were determined by FACS analysis and by TUNEL (apoptosis) in the head, limbs, and liver of the embryos. All tested organs showed apoptosis and a significantly decreased proportion of live cells after 24 h. Subsequent events were organ-dependent. In the liver, there were no dysmorphic events at any time and excessive cell death had been almost compensated for by 48 h. Compensation was preceded by G(1) arrest and accompanied by an increased level of p53 protein in surviving cells. Excessive cell death in the head and the limbs resulted in structural anomalies. In the head, there was an increased level of p53 protein and G(1) arrest after 24 h and the number of live cells at 48 h was equal to that seen in earlier samples, despite apoptosis. In the limbs, however, only isolated viable cells were seen by 48 h, but there was no increased level of p53 protein or G(1) arrest. Results of this study suggest that the differential sensitivity of tested organ systems to CP may be associated with differences in cellular events following CP-initiated cell death. They also suggest that the input of p53 in determining the response of these organ systems to CP-induced teratogenic insult may be different. Teratogenesis Carcinog. Mutagen. 19:353-367, 1999.

Animals↗
PubMed1998

Structural requirements for outside-in and inside-out signaling by Drosophila neuroglian, a member of the L1 family of cell adhesion molecules.

Expression of the Drosophila cell adhesion molecule neuroglian in S2 cells leads to cell aggregation and the intracellular recruitment of ankyrin to cell contact sites. We localized the region of neuroglian that interacts with ankyrin and investigated the mechanism that limits this interaction to cell contact sites. Yeast two-hybrid analysis and expression of neuroglian deletion constructs in S2 cells identified a conserved 36-amino acid sequence that is required for ankyrin binding. Mutation of a conserved tyrosine residue within this region reduced ankyrin binding and extracellular adhesion. However, residual recruitment of ankyrin by this mutant neuroglian molecule was still limited to cell contacts, indicating that the lack of ankyrin binding at noncontact sites is not caused by tyrosine phosphorylation. A chimeric molecule, in which the extracellular domain of neuroglian was replaced with the corresponding domain from the adhesion molecule fasciclin II, also selectively recruited ankyrin to cell contacts. Thus, outside-in signaling by neuroglian in S2 cells depends on extracellular adhesion, but does not depend on any unique property of its extracellular domain. We propose that the recruitment of ankyrin to cell contact sites depends on a physical rearrangement of neuroglian in response to cell adhesion, and that ankyrin binding plays a reciprocal role in stabilizing the adhesive interaction.

Amino Acid Sequence↗
PubMed1998

Mutations of alpha spectrin and labial block cuprophilic cell differentiation and acid secretion in the middle midgut of Drosophila larvae.

Mutations in Drosophila alpha spectrin cause larval lethality and defects in cell shape and adhesion (J. Lee et al., 1993, J. Cell Biol. 123, 1797-1809). Here we examined the effects of two lethal alpha spectrin alleles (alpha-specrg41 and alpha-specrg35) on development and function of the larval midgut. Homozygous null alpha-specrg41-mutant larvae exhibited a striking defect in middle midgut acidification. In contrast, many homozygous alpha-specrg35 mutants were capable of acidification, indicating partial function of the truncated alpha-specrg35 product. Acidification was also blocked by a mutation in the labial gene, which is required for differentiation of cuprophilic cells in the midgut, suggesting that these cells secrete acid. We found that two isoforms of spectrin (alphabeta and alphabetaH) are segregated within the basolateral and apical domains of cuprophilic cells, respectively. The most conspicuous defect in cuprophilic cells from labial and alpha spectrin mutants was in morphogenesis of the invaginated apical domain, although basolateral defects may also contribute to the acidification phenotype. Acid secretion in vertebrate systems is thought to involve the polarized activities of apical proton pumps and basolateral anion exchangers, both of which interact with spectrin. We propose that the alpha-specrg41 mutation in Drosophila interferes with the polarized activities of homologous molecules that drive acid secretion in cuprophilic cells.

Animals↗
PubMed1997

Randomised trial of oral and intravenous methylprednisolone in acute relapses of multiple sclerosis.

BACKGROUND: An intravenous rather than oral course of methylprednisolone is often prescribed for treating acute relapses in multiple sclerosis (MS) despite the lack of evidence to support this route of administration. Our double-blind placebo-controlled randomised trial was designed to compare the efficacy of commonly used intravenous and oral steroid regimens in promoting recovery from acute relapses in MS. METHODS: 42 patients with clinically definite relapse in MS received oral, and 38 intravenous, methylprednisolone. Clinical measurements at entry and at 1 week, 4 weeks, 12 weeks, and 24 weeks included Kurtzke's expanded disability status scale (EDSS), Hauser's Ambulatory Index, and an arm-function index. The primary outcome criterion was a difference between the two treatment groups of one or more EDSS grades at 4 weeks. FINDINGS: There were no significant differences between the two groups at any stage of the study in any measurement taken: the mean difference in EDSS at 4 weeks (adjusted for baseline level) was 0.07 grades more in those taking oral steroids (95% CI -0.46 to 0.60). The most optimistic outcome for intravenous therapy is an average benefit of less than half a grade improvement on EDSS over oral treatment. INTERPRETATION: Since our study did not show any clear advantage of the intravenous regime we conclude that it is preferable to prescribe oral rather than intravenous steroids for acute relapses in MS for reasons of patient convenience, safety, and cost.

Administration, Oral↗
PubMed1995

Cellular polarity in ciliates: persistence of global polarity in a disorganized mutant of Tetrahymena thermophila that disrupts cytoskeletal organization.

Much of the cell surface on the ciliate Tetrahymena thermophila is covered by a polarized lattice of cytoskeletal structures that are associated with basal bodies of the ciliary rows. Unique structural landmarks, including an oral apparatus and contractile vacuole pores, develop before cell division in localized domains located, respectively, posterior and anterior to the transverse fission zone. All of these structures can be visualized by specific monoclonal antibodies. A single-locus recessive mutation, disorganized-A (disA), primarily affects the striated rootlets of the ciliary-row basal bodies and brings about a severe disorganization in the positioning and orientation of these basal bodies and associated cytoskeletal elements. Nonetheless, the new oral apparatus, contractile vacuole pores, and other unique structures appeared at or near their normal sites along the anteroposterior axis of disA cells, indicating that the positioning of these localized structures is not dependent on the integrity of the ciliary rows. Abnormalities were present in the details of construction of some of the localized structures and in aspects of cell shape that may be influenced by these details. In the main, however, analysis of disA mutant cells indicates that intracellular domains near the cell poles develop independently of the vectorial polarity of the ciliary rows.

Alleles↗
PubMed1995

The effects of lithium chloride on pattern formation in Tetrahymena thermophila.

Lithium ions have long been known to exert dramatic effects on the specification of cell fates in multicellular systems. We have analyzed the effects of Li+ on intracellular patterning in a complex unicellular organism, the ciliate Tetrahymena thermophila. LiCl does not affect the locations of major structural landmarks in the cortical region of wild-type cells and does not modify the phenotype of pattern-mutant cells. However, in all strains studied LiCl differentially affects early stages of oral development. It initially triggers a slow regression of oral primordia, which is followed by an excessive proliferation of basal bodies that leads to a hypertrophy of the ciliature of the cell's feeding organelle. This hypertrophy mimics the effects of the membranellar-pattern-D mutation, the phenotype of which is enhanced in the presence of LiCl. These effects were partially reversed by myo-inositol; however, neomycin failed to mimic the effects of LiCl. Thus, although lithium ions have major cellular effects on Tetrahymena, they do not influence the specification of the body plan in a manner analogous to that observed in multicellular organisms and may work in part through mechanisms other than the now-classical inositol-phosphate cycle.

Animals↗
PubMed1995

Efficacy of postoperative 5-FU, high-dose leucovorin, and sequential radiation therapy for clinically resectable rectal cancer.

We report the local control and survival in a previously reported phase I dose escalation trial of combined postoperative 5-FU, high dose leucovorin (LV), and sequential radiation therapy followed by maintenance LV/5-FU for the treatment of patients with clinically resectable rectal cancer. Following surgery for stages T3-4N0-2M0 primary (21) or recurrent (4) rectal cancer, 25 patients received 5-FU/LV x 1 cycle. Radiation therapy (5040 cGy) began on day 8. A second cycle of 5-FU/LV was given concurrent with the fourth week of radiation. Patients received an additional 10 cycles of LV/5-FU. The median follow-up was 40 months (range 18-52). The incidence of grade 3+ acute toxicity in the 9 patients who received the recommended dose of 5-FU was 44%. The local failure rate was 28%. Abdominal and distant failure rates were 24%. The 3-year actuarial disease-free survival was 74% and the overall survival was 80%. Our preliminary data reveal reasonable local control and survival rates. However, further follow-up is needed to assess our results at 5 years. Postoperative combined modality therapy with high-dose LV may be an option for the adjuvant treatment of patients with resectable rectal cancer.

Adenocarcinoma↗