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Biomedical subjects

M Frankel

Publications and source records attributed to M Frankel.

At least 37 records · Page 2Linked to original sources
PubMed1997

Epidermal growth factor and betacellulin mediate signal transduction through co-expressed ErbB2 and ErbB3 receptors.

Interleukin-3 (IL-3)-dependent murine 32D cells do not detectably express epidermal growth factor receptors (EGFRs) and do not proliferate in response to EGF, heregulin (HRG) or other known EGF-like ligands. Here, we report that EGF specifically binds to and can be crosslinked to 32D transfectants co-expressing ErbB2 and ErbB3 (32D.E2/E3), but not to transfectants expressing either ErbB2 or ErbB3 individually. [125I]EGF-crosslinked species detected in 32D. E2/E3 cells were displaced by HRG and betacellulin (BTC) but not by other EGF-like ligands that were analyzed. EGF, BTC and HRG also induced receptor tyrosine phosphorylation, activation of downstream signaling molecules and proliferation of 32D.E2/E3 cells. 32D transfectants were also generated which expressed an ErbB3-EGFR chimera alone (32D.E3-E1) or in combination with ErbB2 (32D. E2/E3-E1). While HRG stimulation of 32D.E3-E1 cells resulted in DNA synthesis and receptor phosphorylation, EGF and BTC were inactive. However, EGF and BTC were as effective as HRG in mediating signaling when ErbB2 was co-expressed with the chimera in the 32D.E2/E3-E1 transfectant. These results provide evidence that ErbB2/ErbB3 binding sites for EGF and BTC are formed by a previously undescribed mechanism that requires co-expression of two distinct receptors. Additional data utilizing MDA MB134 human breast carcinoma cells, which naturally express ErbB2 and ErbB3 in the absence of EGFRs, supported the results obtained employing 32D cells and suggest that EGF and BTC may contribute to the progression of carcinomas that co-express ErbB2 and ErbB3.

Animals↗
PubMed1997

Jak1 expression is required for mediating interleukin-4-induced tyrosine phosphorylation of insulin receptor substrate and Stat6 signaling molecules.

The Jak1, Jak2, Jak3, and Fes tyrosine kinases have been demonstrated to undergo tyrosine phosphorylation in response to interleukin (IL)-4 stimulation in different cell systems. However, it is not clear which, if any, of these kinases are responsible for initiating IL-4-induced tyrosine phosphorylation of intracellular substrates in vivo. In the present study, we have utilized a mutant Jak1-deficient HeLa cell line, E1C3, and its parental Jak1-expressing counterpart, 1D4, to analyze the role of Jak1 in mediating IL-4-induced tyrosine phosphorylation events. IL-4 treatment rapidly induced tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and IRS-2 in 1D4 but not in E1C3 cells. IL-4-mediated tyrosine phosphorylation of Stat6 was pronounced in 1D4 cells, while no IL-4-induced Stat6 phosphorylation was detected in E1C3 cells. IL-4 also induced Stat6 DNA binding activity from lysates of 1D4 but not E1C3 cells utilizing a radiolabeled immunoglobulin heavy chain germline epsilon promotor sequence (Iepsilon) in an electrophoretic mobility shift assay. Reconstitution of Jak1 expression in E1C3 cells restored the ability of IL-4 to induce IRS and Stat6 tyrosine phosphorylation. These results provide evidence that Jak1 expression is required for mediating tyrosine phosphorylation and activation of crucial molecules involved in IL-4 signal transduction.

HeLa Cells↗
PubMed1995

Signal transduction through the IL-4 and insulin receptor families.

Activation of tyrosine kinase-containing receptors and intracellular tyrosine kinases by ligand stimulation is known to be crucial for mediating initial and subsequent events involved in mitogenic signal transduction. Receptors for insulin and insulin-like growth factor 1 (IGF-1) contain cytoplasmic tyrosine kinase domains that undergo autophosphorylation upon ligand stimulation. Activation of these receptors also leads to pronounced and rapid tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) in cells of connective tissue origin. A related substrate, designated 4PS, is similarly phosphorylated by insulin and IGF-1 stimulation in many hematopoietic cell types. IRS-1 and 4PS possess a number of tyrosine phosphorylation sites that are within motifs that bind specific SH2-containing molecules known to be involved in mitogenic signaling such as PI-3 kinase, SHPTP-2 (Syp) and Grb-2. Thus, they appear to act as docking substrates for a variety of signaling molecules. The majority of hematopoietic cytokines bind to receptors that do not possess intrinsic kinase activity, and these receptors have been collectively termed as members of the hematopoietin receptor superfamily. Despite their lack of tyrosine kinase domains, stimulation of these receptors has been demonstrated to activate intracellular kinases leading to tyrosine phosphorylation of multiple substrates. Recent evidence has demonstrated that activation of different members of the Janus family of tyrosine kinases is involved in mediating tyrosine phosphorylation events by specific cytokines. Stimulation of the interleukin 4 (IL-4) receptor, a member of the hematopoietin receptor superfamily, is thought to result in activation of Jak1, Jak3, and/or Fes tyrosine kinases.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

The effect of trauma and confinement on functional health and mental health status of Cambodians living in Thailand-Cambodia border camps.

OBJECTIVE: To assess the long-term impact of trauma and confinement on the functional health and mental health status of Cambodian displaced persons living on the Thailand-Cambodia border. DESIGN: Household survey of 993 adults randomly selected from household rosters. Household sample selection by multistage area probability sample. SETTING: Site 2, the largest Cambodian displaced-persons camp on the Thailand-Cambodia border. PARTICIPANTS: Adults 18 years of age and older selected at random within households; 98% of eligible persons selected agreed to participate. RESULTS: From 1975 through 1979 (Khmer Rouge regime), more than 85% reported lack of food, water, shelter, and medical care, brainwashing, and forced labor; 54% reported murder of a family member or friend; 36% reported torture; 18% reported head injury; and 17% reported rape or sexual abuse. During the refugee period between 1980 and 1990, 56% reported lack of food or water, 44% reported lack of shelter, 28% reported lack of medical care, 24% reported brainwashing, and 8% reported torture. Since 1980, reports of murder of a family member, head injury, and rape/sexual abuse have decreased to 5%. Reports of experiencing combat situations and shelling attacks have remained consistent between the two time periods, approximately 44% and 30%, respectively. From 1989 to 1990, 25% reported experiencing lack of food or water, and 5% to 10% reported serious injury, combat, and shelling conditions. More than 80% said they were in fair or poor health, felt depressed, and had a number of somatic complaints despite good access to medical services. Fifty-five percent and 15% had symptom scores that correlate with Western criteria for depression and posttraumatic stress disorder, respectively. Fifteen percent to 20% reported health impairments limiting activity, and moderate or severe bodily pain. Despite reported high levels of trauma and symptoms, social and work functioning were well preserved in the majority of respondents. CONCLUSIONS: Reports of extensive trauma, poor health status, and depressive symptoms of this population are of concern in predicting future morbidity and mortality. The health and mental health needs of Cambodian displaced persons and their impact on social and economic behavior should be addressed now that the Cambodians have been repatriated.

Adult↗
PubMed1992

The uninsured and the debate over the repeal of the Massachusetts universal health care law.

OBJECTIVES: The debate in Massachusetts over the repeal of the first state-based "pay or play" universal health plan is discussed using data from a survey of 1066 Massachusetts households. The survey attempted to measure the problems of the uninsured, to estimate the likelihood that they would buy insurance if offered, and to calculate the proportion of the uninsured who would be covered under an employer mandate. DESIGN: A survey conducted in person and by telephone in 1066 households, with an oversample of uninsured households, using stratification, clustering, disproportionate sampling, and poststatistical weighting. PARTICIPANTS: Adults aged 18 years and older who were knowledgeable about the insurance status of persons in their household. MAIN OUTCOME MEASURES: Insurance status, employment status, access to and use of health services, and willingness to purchase health insurance. RESULTS: First, the present system of hospital-based uncompensated care in Massachusetts is inadequate by itself to meet the needs of uninsured residents. Uninsured persons are less likely than insured ones to seek medical care for chronic health problems and serious symptoms requiring evaluation. Second, 83% of uninsured families and 24% of uninsured individual respondents would purchase one of several insurance options with 30% of the cost subsidized. Last, the employer mandate provisions of the legislation would cover 43% of the uninsured in Massachusetts. CONCLUSION: In the current economic climate, the political viability of the universal health care plan and similar national initiatives is uncertain given the intractable conflict between perceptions of the financial stability of small businesses that do not offer insurance and the health care needs of uninsured individuals.

Cluster Analysis↗
PubMed1989

A pedigree primer.

Pedigree-taking skills can promote an understanding of how genetic information relates to a comprehensive family health assessment. The format of the pedigree is used to structure and organize data gathered in the assessment process. The pedigree can assist the nurse and genetics specialist to identify possible patterns of inheritance. This article outlines for the staff nurse the pertinent areas that need to be explored during the assessment process. It discusses common terms and symbols used in the pedigree. Information gathered from the health assessment of an adolescent with Usher's syndrome is used for an example of how the pedigree is constructed.

Adolescent↗
PubMed1986

Obsessions and compulsions in Gilles de la Tourette's syndrome.

The incidence of obsessive-compulsive disorder (OCD) in patients with Gilles de la Tourette's syndrome (GTS) was assessed with a specially designed questionnaire. The Inventory was administered to patients with OCD, patients with GTS, and normal controls. Fifty-one percent of the patients with GTS had significantly elevated Inventory scores. The frequent occurrence of OCD in GTS suggests that the two disorders may share common neurobiologic mechanisms.

Adolescent↗
PubMed1985

Gilles de la Tourette syndrome and the neurological basis of obsessions and compulsions.

Gilles de la Tourette syndrome (GTS) is a chronic neurological disorder manifested by involuntary motor tics and vocalizations. Many GTS patients also suffer from obsessions and compulsions. The clinical similarities between GTS and obsessive-compulsive disorder (OCD), their occurrence among members of the same families, and the fact that both can be observed as symptoms of known basal ganglia disturbances suggest that GTS and OCD share common neurological mechanisms. It is hypothesized that the tics and vocalizations of GTS are aberrant manifestations of simple motor programs that are spontaneously generated by the basal ganglia and that obsessions and compulsions represent more complex motor plans initiated by similar anomalous activities.

Basal Ganglia↗
PubMed1985

Predictors of dentists' level of knowledge regarding the recommended prophylactic regimen for patients with rheumatic heart disease.

Maintaining knowledge of clinical practices, conforming to the latest scientific information, is a major challenge for health professionals. The study aims were to measure clinicians' knowledge and to determine what social factors could best explain and predict those dental clinicians who are most knowledgeable about current expert recommendations for the use of appropriate antibiotic regimens for patients at risk for bacterial endocarditis. Telephone interviews were conducted with 322 New York State dentists, assigned to the study by a computer-generated randomization procedure from lists of oral surgeons, urban general practitioners and rural general practitioners. Data demonstrated extraordinary differences in level of knowledge between oral surgeons and general practitioners, while the level of knowledge between urban and rural general practice groups was quite similar. General Linear Model (GLM)-based analyses indicated that practice size, rationalization of practice, and practice setting and affiliations contributed to the explanation of knowledge level among general practitioners, when adjusted for age. R2s for each of those variables and age, ranged from a low of 0.132 to a high of 0.334. Age made a significant contribution to the explanation of knowledge level in all of the models presented, while the explanatory power of the practice structure variables varied according to respondent's locale (urban vs rural) and age (younger vs older). In order to assess the impact of these structural variables, they were dichotomized (high-low) and entered into a GLM program which accounted for age and locale. Differences in excess of 20 points (on a 0-100 knowledge scale) were sometimes noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1983

The human Klüver-Bucy syndrome.

Twelve patients with the Klüver-Bucy syndrome (KBS) are described. The syndrome occurred in head trauma, Alzheimer's disease, Pick's disease, and following herpes encephalitis. KBS was transient after head trauma but was a persistent feature of the postencephalitic syndrome. In all cases KBS was combined with aphasia, amnesia, or dementia. Human KBS resembles the monkey syndrome, but in humans there is a more elaborate complex of behavioral disturbances. The behavioral manifestations are produced by bilateral temporal lobe dysfunction. Partial expression of the syndrome may have localizing validity.

Adult↗
PubMed1981

New data on lithium and haloperidol incompatibility.

The authors describe a case of combined lithium and haloperidol toxicity characterized by hyperpyrexia, severe rigidity, mutism, and development of irreversible tardive dyskinesia. This case is similar to four other cases described in the literature and to the neuroleptic malignant syndrome. The authors postulate that two types of combined lithium-neuroleptic toxicity occur: a neuroleptic malignant extrapyramidal syndrome and a lithium toxicity that occurs in combination with phenothiazines, primarily thioridazine. Possible mechanisms and preventive measures are discussed.

Antipsychotic Agents↗
PubMed1980

Otogenic pneumocephalus secondary to chronic otitis media.

Spontaneous pneumocephalus is currently a rare manifestation of chronic otitis media. Although a rarity, the diagnosis must be considered when a patient has neurologic complaints and chronic otitis media. Despite the importance of early recognition and treatment in preventing potentially fatal complications, it has been noticeably neglected in recent otolaryngologic literature. We report a case, review the literature, and discuss the related pathophysiology. This case demonstrates the need for at least skull roentgenograms in patients with positive neurologic history and chronic otitis media and the danger of neglecting the proper treatment of cholesteatoma.

Aged↗
PubMed1977

Investigation of the non-jaundiced patient by percutaneous transhepatic cholangiography.

The investigation of the non-jaundiced patient by percutaneous transhepatic cholangiography (PTC) and the indications for this examination are presented. Diagnostic examinations were obtained in all 15 patients studied despite the absence of jaundice at the time of examination. Complications were minimal. The value of this method particularly after previous biliary surgery is emphasized. It is suggested that PTC may be of great value, and safely used in non-jaundiced patients.

Adult↗