Search PubMed⌕ Search

Biomedical subjects

M Kaufman

Publications and source records attributed to M Kaufman.

At least 127 records · Page 7Linked to original sources
PubMed1987

Partial androgen resistance due to a distinctive qualitative defect of the androgen receptor.

Using whole genital skin fibroblasts, we have characterized a novel androgen receptor mutation in a family with partial androgen resistance. The proposita was born with bilateral labioscrotal folds and a single perineal urogenital orifice. Her similarly affected maternal aunt was raised as a female with the support of gonadectomy and vaginoplasty. The mutant androgen receptor has a normal maximum binding capacity (Bmax), but an increased apparent equilibrium dissociation constant (Kd) with 5 alpha-dihydrotestosterone (DHT) and 2 synthetic androgens, methyltrienolone (MT) and mibolerone (MB). Preformed mutant DHT-receptor complexes dissociate (k) at a near-normal rate, but their MT and MB counterparts dissociate twice as quickly as normal. The native free mutant receptor is not more thermolabile than normal, but its recently dissociated counterpart is. Prolonged incubation of the cells with each of the 3 androgens causes the mutant receptor to acquire a normal increment of increased androgen-receptor activity. This androgen-sensitive pattern of misbehavior of the present mutant receptor distinguishes it from those responsible for 3 other families with partial androgen resistance studied previously. These differences will help to identify structure-function domains on the androgen receptor protein, particularly in conjunction with the use of DNA probes to analyze mutations at the X-linked androgen receptor locus.

Androgen-Insensitivity Syndrome↗
PubMed1987

Biological activity, binding, and metabolic fate of Ac-[Nle4, D-Phe7]alpha-MSH4-11NH2 with the F1 variant of B16 melanoma cells.

The alpha-MSH (alpha-melanocyte-stimulating hormone) agonist, Ac-[Nle4, D-Phe7]alpha-MSH4-11NH2 (hereafter called ND4-11 alpha-MSH), is at least 10-fold more potent than alpha-MSH as a stimulus of tyrosinase activity in F1 variant cells of B16 melanoma. The binding to these cells during an incubation with 5 nM (3H)ND4-11 alpha-MSH at 37 degrees C is maximal at 0-30 min, 22 fmol/10(6) cells, but declines to 40% of this value at 4 hr. in the presence of 5 nM (3H)ND4-11 alpha-MSH at 37 degrees C, the acid soluble (cell surface) radioactivity decreased rapidly from 11.4 fmol/10(6) cells at 5 min to 4.6 fmol/10(6) cells at 4 hr. Chromatographic analysis of media and cellular samples revealed that there was no evidence of degradation of (3H)ND4-11 alpha-MSH in the medium but there was evidence of intracellular degradation of (3H)ND4-11 alpha-MSH. Ammonium chloride (10mM) resulted in an increase in acid resistant radioactivity (internalized hormone) at 4 hr. The binding to F1 variant cells during an incubation with 0.155 nM or 5 nM (3H)ND4-11 alpha-MSH at 4 degrees C was constant from 4 hr to 24 hr. Under these conditions, there was no time-dependent change in the acid soluble radioactivity from 4 to 24 hr. Scatchard analysis of (3H)ND4-11 alpha-MSH binding to F1 variant cells at 4 degrees C demonstrated that there were approximately 4500 receptors per cell and an association constant of 17.1 nM-1. These results are consistent with a process of (3H)ND4-11 alpha-MSH binding to its receptor followed by internalization of the receptor-hormone complex and then intracellular degradation of the hormone.

Ammonium Chloride↗
PubMed1987

Extracellular correction of the androgen-receptor transformation defect in two families with complete androgen resistance.

We have characterized the cellular and extracellular phenotype of the mutant androgen receptor (AR) from two families who have complete androgen resistance despite a normal androgen-binding capacity (Bmax) in their genital skin fibroblasts (GSF). The cellular receptors fail to up-regulate their basal AR activity in response to prolonged incubation with 5 alpha-dihydrotestosterone (DHT), or with two synthetic androgens, methyltrienolone (MT) and mibolerone (MB), and form A-R complexes with increased equilibrium (Kd) and non-equilibrium (k) dissociation constants. In addition, they are thermolabile when recently dissociated, but not in their native state. A-R complexes made in normal or mutant cytosol at 4 degrees C elute from DEAE-Sephacel at approximately 0.25 M KCl (untransformed), with or without prior passage through Sephadex G-25; when made in cells at 37 degrees C, extracted with 0.4 M KCl in a buffer containing 10 mM Na2MoO4, and desalted by G-25, they elute at less than or equal to 0.1 M KCl. Normal KCl-extracted DHT- and MB-R complexes dissociate (37 degrees C) at the same slow, linear rate as their in-cell counterparts (transformed); the mutant ones dissociated more slowly than their rapidly-dissociating in-cell counterparts and, to a variable extent, nonlinearly-an early faster phase, a later slower (transformed). Thus, as judged by two conventional criteria of steroid-R complex transformation, the mutant A-R complexes can transform, possibly in two steps, under certain cell-free conditions. This behavior differentiates a class of structural AR mutations whose molecular definition awaits application of recombinant DNA techniques to the X-linked AR locus.

Androgens↗
PubMed1987

Progress toward meeting the 1990 nutrition objectives for the nation: nutrition services and data collection in state/territorial health agencies.

Promoting Health, Preventing Disease, Objectives for the Nation, specifies nutrition as a priority area for improving the health of Americans by 1990. Eleven of the 15 nutrition objectives target adults or the public while four address pregnant and lactating women, infants, and children. To determine progress by states toward achieving the nutrition objectives, the Association of State and Territorial Public Health Nutrition Directors conducted a survey in 1985 to which 54 state and territorial nutrition directors responded. Three-fourths of the nutrition personnel focused efforts on maternal and child populations, and were supported largely by federal funds from the Special Supplemental Food Program for Women, Infants, and Children (WIC) and the Maternal and Child Health Block Grant. Only 15 per cent were funded by state and local sources. While most agencies reported using nutrition consultation in adult health programs, only 25 per cent paid for these personnel. Data to monitor progress were commonly available for only five of the 15 objectives. Achievement of the nutrition objectives by states will require a more comprehensive approach to nutrition programming with increased allocation of appropriate resources and expansion of health data systems.

Adolescent↗
PubMed1987

Fine-needle aspiration biopsy in diagnosis of pulmonary masses.

Fine-needle aspiration biopsy (FNAB) is a diagnostic method indicated in patients with pulmonary lesions that cannot be reached with a bronchoscope and when cytologic examinations of the sputum are persistently negative. Cells are aspirated under fluoroscopic control and stained using the Papanicolaou method for cytologic examination. Results are available within hours, and the material can be used for other studies. Between 1975 and 1984, the authors performed 845 FNABs in 342 patients. Diagnosis was established in 306 patients, or 89.5 per cent. Malignant neoplasm was diagnosed in 284 instances, benign disease in 22. In 176 patients with malignant tumors, the diagnosis was based on FNAB exclusively. In 108 patients who were operated on, the results of FNAB matched histology in 97 per cent. The aspiration specimen was inadequate in 36 patients, most of whom had diffuse lung disease. The incidence of complications was extremely low. FNAB is safe and reliable. It is recommended for use in clinical workup of undiagnosed pulmonary masses. FNAB enables rational planning of treatment when other diagnostic methods fail. The authors do not recommend FNAB for use in cases of diffuse pulmonary disease.

Adult↗
PubMed1986

Ligand-specific thermal misbehavior of synthetic androgen-receptor complexes in genital skin fibroblasts of subjects with familial ligand-sensitive androgen resistance.

We have used 5 alpha-dihydrotestosterone (DHT) and two synthetic, non-metabolizable androgens, methyltrienolone (MT) and mibolerone (MB), to study intact genital skin fibroblasts from four subjects with familial incomplete androgen resistance. In each, the free androgen receptor has normal binding capacity at 37 degrees C and normal half-lives at 37-43 degrees C. In three the mutant receptor misbehaves in a pattern that is ligand-specific and temperature-dependent. At 37 degrees C the equilibrium (Kd) and non-equilibrium (k) dissociation constants, and the ability to augment binding activity during prolonged exposure to androgen, are impaired with DHT, but not with MT; with MB, only the k is abnormal. Mutant MT-receptor complexes dissociate normally even at 42 degrees C; yet, in cells post-incubated at 42 degrees C with cycloheximide and a saturating concentration of ligand, their pool size decays in the rank order, MT greater than MB greater than normal. This measure of lability is nonlinear as a semilogarithmic function of time; it varies directly with temperature and the concentration of cycloheximide, but inversely with that of ligand. Thus, MT and MB evoke distinct forms of thermal dysfunction from the androgen receptor in ligand-sensitive androgen resistance. This observation will help to elucidate the combinatorial properties of normal androgen-receptor complexes that enable them to regulate gene transcription differentially in various androgen target tissues.

Androgens↗
PubMed1986

The use of talc for pleurodesis in the treatment of resistant empyema.

The use of talc in the infected pleural space has not been reported previously. Five patients who had empyema of the pleura in the fibrinopurulent stage and did not respond to treatment with tube drainage and antibiotics were treated by talc insufflation to stimulate pleural adhesions. Pleurodesis was achieved in all 5 patients, with complete recovery from empyema. No untoward effects were observed. These results suggest that talc pleurodesis may be an acceptable solution to the problem of empyema resistant to other methods of treatment.

Adult↗
PubMed1986

Survey of nutritionists in state and local public health agencies.

A spring 1985 survey of 50 state and four territorial public health nutrition directors identified 2,931 budgeted positions for public health nutritionists--1,128 in state agencies and 1,803 in local health departments. To achieve the recommended staffing ratio of one public health nutritionist per 50,000 population, an estimated 1,827 more public health nutritionists are needed nationwide with more needed in some states than in others. About half of the state personnel systems require registration or registration eligibility to assure expertise of public health nutrition personnel; about one-third also require graduate training in public health for leadership, planning, and policymaking positions. Sixty-two percent of the funding for state and local health agency nutritionist positions is from the Special Supplemental Food Program for Women, Infants, and Children (WIC). When that is added to the 11% of funds from the Maternal and Child Health Block Grant, 73% of the public health nutritionist positions are federally supported to serve women of childbearing age, infants, and children. That leaves the remaining state and local funding sources and the federal Prevention Block Grant (2%) to pay salaries of nutritionists to serve the general public, including men, postmenopausal women, and the elderly.

Data Collection↗
PubMed1986

Preparing public health nutritionists to meet the future.

Public health nutrition personnel have been defined as those specialized nutrition professionals and paraprofessionals who provide nutrition services through agencies whose mandate is health protection and promotion, disease prevention, and/or primary care to people in the community. Educators preparing graduate level nutritionists for future demands of federal, state, and local public health programs must read the scientific, technological, and societal trends, including changes in demographics, health delivery systems, communications technologies, and consumer demands. As research more clearly defines the role of nutrition and diet in human health, nutritionists should be educated to monitor trends and be proactive in seeking emerging opportunities. It is nutritionists' responsibility to assure that scientific findings in nutrition, dietetics, and food science are considered in policy formulation as well as in the technical input into agency and community programs. The nutritionist who understands the changing values and life-styles of diverse populations uses acceptable techniques to motivate any necessary behavior changes. To be effective in the community, he/she uses community assessment, epidemiological, and program planning skills basic to public health practice. In the current climate of cost containment, the public health nutritionist will successfully compete for dwindling funds by managing programs with skill and documenting cost benefits and cost-effectiveness.

Dietetics↗
PubMed1985

Towards a logical analysis of the immune response.

We present a new way to conceive, formalize and analyse models of the immune network. The models proposed are minimal ones, based essentially on the well-established negative feedback loop between helper and suppressor T cells. The occurrence of T-T interactions in both helper and suppressor circuits. These T-T interactions are represented here by autocatalytic feedback loops on TH and TS. The fact that immature B cells are sensitive to negative signaling, as was originally suggested by Lederberg (1959). There is a functional inactivation of immature B cells encountering antigen or anti-idiotypic antibody. This prevents further differentiation to a stage where the B cells become fully responsive. We describe the role of a logical method in the generation and analysis of the models, and the complementarity between this logical method and the more classical description by continuous differential equations. Logical analysis and numerical simulations of the differential equations show that the emerging model accounts for, the occurrence of multiple steady states (a virgin state, a memory state and a non-responsive state) in the absence of antigen, the kinetics of primary and secondary responses, high dose paralysis, low dose of paralysis. Its fit with real situations is surprisingly good for a model of this simplicity. Nevertheless, we give it as an example of what can now be done in the field rather than as a stable model.

Antibody Formation↗