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Biomedical subjects

M Kaufman

Publications and source records attributed to M Kaufman.

At least 109 records · Page 6Linked to original sources
PubMed1989

Impaired spermatogenesis is not an obligate expression of receptor-defective androgen resistance.

We are studying a man who presented at age 21 years with severe extragenital subvirilization despite high-normal to above-normal levels of plasma testosterone for at least 5 years. At puberty, his penis, scrotum, and testes matured normally, and he did not develop gynecomastia; however, his voice, muscularity, and facial, sexual, and body hair remained immature. A 2.5-ml ejaculate yielded normal results for sperm density, morphology, and motility. Because persistent undervirilization was emotionally disabling, he has received pharmacologic doses of testosterone enanthate intramuscularly for 3.5 years. The treatment has improved his virilization and masculine self-image substantially, and his semen analysis has remained well within the normal range. The androgen receptor in his genital skin fibroblasts has a distinctively mutant phenotype: it has a low affinity (increased apparent equilibrium dissociation constant, Kd) for 5 alpha-dihydrotestosterone and two synthetic androgens, mibolerone (MB) and methyltrienolone (MT), and its binding capacity (Bmax) is normal for the other two ligands, but questionably low for MT. In addition, it up-regulates its activity normally in response to prolonged incubation with androgen, and its androgen-receptor complexes are not thermolabile. Our study of this man permits two conclusions: impaired spermatogenesis is not the irreducible expression of receptor-defective androgen resistance in man; and androgen pharmacotherapy may be remedial for those in whom extragenital subvirilization is emotionally costly and subnormal spermatogenesis is not an inevitable side effect of such therapy.

Adult↗
PubMed1989

Ultracentrifugal analysis of the junction complexes of the red cell membrane cytoskeletal network: application to hereditary spherocytosis and metabolically depleted cells.

A method has been developed for the assessment of the number of spectrin dimer units associated with each actin protofilament junction, in the membrane cytoskeletal network (i.e. the degree of branching) of the red cell. Ghosts are first exposed to elevated temperature at low ionic strength to dissociate some 65% of the spectrin tetramers (that link the network junctions) into dimers, without causing their release from the actin filaments. Non-ionic detergent is then added to solubilize the membrane itself with its intrinsic proteins, so as to liberate the cytoskeletal material, and the mixture is immediately examined in the analytical ultracentrifuge. The predominant components observed are isolated junctions (20 S), free spectrin dimers and the residual undissociated cytoskeletal material, with very minor components, probably corresponding to multiple junctions, linked by spectrin tetramers. The junction boundary is homogeneous within the accuracy of measurement and is taken to correspond to a complex containing six spectrin dimers, known to predominate in situ. About 17% of the total network is liberated in this form and 12% as free spectrin dimers. In hereditary spherocytosis both the size of the junction complex (as reflected by its sedimentation coefficient) and the proportion of the complex and of free spectrin liberated are indistinguishable from normal values. We conclude that the reported deficit of spectrin in hereditary spherocytosis is not reflected by a lower degree of branching of the network, and, if the membrane area is not correspondingly reduced, this must mean that the junctions are more widely spaced and the spectrin tetramers therefore more extended. In metabolically depleted cells, in which the cytoskeletal proteins are known to be extensively dephosphorylated, there is no change in the sedimentation pattern and thus no detectable loss of spectrin from the junctions or weakening in the cohesion of the cytoskeletal network.

Actins↗
PubMed1989

A single-site allosteric model of intracellular androgen-receptor interaction.

We present a single-site, two-state model for analyzing the effect of time and ligand concentration on the extent and character of 5 alpha-dihydrotestosterone, methyltrienolone or mibolerone binding to the specific androgen receptor within cultured human genital skin fibroblasts. The model has three basic attributes: formation of the initial low-affinity androgen-receptor complex, and its transformation to a higher affinity state are irreversible, first-order processes; and receptors released from complexes in each state not only differ from each other and from their pre-liganded progenitor, but can also reassociate with androgen to yield complexes in their respective parental states. The rate constants of dissociation and apparent equilibrium binding constants of the two affinity states were determined for each of the three androgens within normal cells and those of a transformation-defective mutant. When these values are combined with estimates of the rate constants at which the complexes are formed and transformed, the model accurately simulates time-dependent changes in the slopes and character of experimental Scatchard plots. It can also generate Scatchard plots that are concave, convex or sigmoidal simply by making sequential changes in its formation or transformation constants. Thus, our model can explain complex ligand-receptor binding kinetics that have heretofore been interpreted according to alternate models of transformation and binding-site multiplicity with or without properties of cooperativity, and it supports the notion that receptor recycling involves intermediate receptor states.

Allosteric Regulation↗
PubMed1989

Are dietitians prepared to work with handicapped infants? PL 99-457 offers new opportunities.

PL 99-457 mandates nutrition as one of eight disciplines to be included on the team providing services to handicapped infants (up to age 3) and their families. A case-managed range of services is required to enable the child to benefit from early interventions. Findings from a survey of a sample of entry-level Plan IV/V Programs, Coordinated Programs in Dietetics, and dietetic internships randomly selected from The American Dietetic Association's 1988 Directory of Dietetic Programs indicate that the growth and development of handicapped infants and their nutrition care are underexposed in most didactic and experiential components of the education of entry-level dietitians. A working group of nine nutritionists with expertise in both dietetic education and nutrition care of handicapped children met at a national conference and recommended competencies that they thought would enable entry-level registered dietitians to join interdisciplinary teams working with handicapped infants and their families. Registered dietitians on the team that prepares the Individualized Family Service Plan (IFSP) can strive to ensure that infants are well nourished and therefore more responsive to the other therapies proposed in the plan.

Child, Exceptional↗
PubMed1988

An abundant 56 kD protein with low affinity androgen binding: another member of the steroid/thyroid receptor family?

We have found in genital skin fibroblasts an abundant 56 kD protein which appears related to the androgen receptor. The protein is detected in the soluble fraction by two-dimensional polyacrylamide gel electrophoresis as two spots with isoelectric points of 6.7 and 6.5 respectively. Photoaffinity labelling of GSF with 8 nM or 50 nM [3H]-methyltrienolone selectively labels the two protein spots but with an apparently lower affinity than is known for the androgen receptor. The two protein spots stem from one protein as judged from peptide patterns of partial proteolytic digests and the equal labelling of both spots with methyltrienolone. Cells from subjects with mutant androgen receptors generally lack the 56 kD protein and labelling with methyltrienolone fails, but the protein is not the androgen receptor itself. We propose the hypothesis that the 56 kD protein is synthesized from the same gene as the androgen receptor and that androgen may not be its natural ligand.

Androgens↗
PubMed1988

Clinical stages of dementia and the dexamethasone suppression test.

1. This study was undertaken to evaluate the relationship between clinical aspects of primary degenerative dementia and suppression or non-suppression in the dexamethasone suppression test. 2. We studied 34 male patients with primary degenerative dementia (as diagnosed by DSM-III criteria). Dexamethasone 1 mg p.o. was administered at 11:00 PM and blood was drawn for cortisol determination at 4:00 PM the next day. 3. CLINICAL FACTORS INCLUDED: age, age at onset, duration of dementia, history of psychiatric illness, severity as measured by Global Deterioration Scale (GDS) score, and "malignancy" of dementia (rated by years of onset to institutionalization and as a ratio of Global Deterioration Scale to duration of primary degenerative dementia). 4. RESULTS: 56% of primary degenerative dementia patients failed to suppress. The highest degree of non-suppression was seen in Global Deterioration Scale 5 and 6 subjects (Table). 5. An unexpected finding was that a large number of Global Deterioration Scale 7 patients demonstrated normal post-dexamethasone suppression of the hypothalamic-pituitary-adrenal axis. 6. Some contradictions in previously reported studies may be explained by this pattern.

Aged↗
PubMed1988

Promoting breastfeeding at a migrant health center.

A program to promote breastfeeding was introduced at a migrant health center in North Carolina. Strategies for promoting breastfeeding as a feeding method particularly suited to the migrant lifestyle were identified and implemented. Donated layettes were used to encourage attendance of prenatal patients at a class on breastfeeding. Women planning to breastfeed were given cards to alert the delivering hospital of their intention. These hospitals were provided with bilingual flipcharts to use in communicating with non-English speaking patients. Of the 158 women who came to the center for one or more prenatal visits, 101 attended a class or received individual counseling on breastfeeding; during this 13-month period, 52 per cent of 64 women who attended the class were breastfeeding at time of their hospital discharge (Mexican-Americans 60%, Black Americans 44%). In a comparison of similar ethnic distribution, the corresponding rate was 10%.

Black or African American↗
PubMed1988

Nutrition services in state and local public health agencies: how do we measure up in 1987?

In 1987, a second biennial mail survey of public health nutritionists in 54 state official public health agencies identified 2,048 budgeted positions compared with 2,931 in 1985, a 30% loss in the state and local health agencies. To achieve the recommended staffing ratio of one public health nutritionist per 50,000 population for policy, program planning, and program management, an estimated 2,812 more nutritionists are needed for a total of 4,850, or a 60% increase. The number of state personnel systems requiring graduate public health training decreased from 19 to 6, while the number requiring R.D./registration eligibility increased from 24 to 33. Fifty-five percent of positions for public health nutritionists are funded from the Special Supplemental Food Program for Women, Infants, and Children, and 10% from the Maternal and Child Health Block Grant. Positions funded from state general revenue doubled from 8% in 1985 to 15% in 1987, while local revenue stayed at about 10%. The midpoint of state salary ranges for the public health nutritionists varied from $14,310 to $38,310. Perceived constraints to expanding nutrition services were inadequate state funding, low agency visibility, and low legislative priority. At a time when consumer interest in nutrition is high and research associates dietary factors with major public health problems, the challenge is to advocate more aggressively for public health nutrition services and funding.

Food Services↗
PubMed1988

Recurrent intracranial hemorrhage in an adult with moyamoya disease: case report, radiographic studies and pathology.

Moyamoya disease is an unusual vascular disorder highlighted by progressive bilateral internal carotid artery occlusion and collateralization of intracranial blood flow. Recurrent multifocal cerebral ischemic events and isolated intracerebral hemorrhage are known to occur in this disorder. We report a 52 year old man who over a nine year period had four apparent intracranial hemorrhages. Serial angiograms demonstrated the evolution of moyamoya disease. Pathologic examination confirmed multiple vascular lesions, including two that were clinically silent.

Adult↗
PubMed1988

A study of androgen-resistant subjects indicates that the 6.7 pI/56 kDa protein in genital skin fibroblasts is related to the androgen receptor.

Two-dimensional gel electrophoresis of cultured human skin fibroblast lysates reveals a silver-stained "spot" of molecular mass 56 kilodaltons (kDa) and isoelectric point (pI) 6.7, occasionally as part of a doublet with a minor pI 6.5 partner. Its presence in each of 23 genital skin fibroblast strains (6 labium majus, 17 prepuce) and its absence in 30 of 32 control non-genital skin fibroblast strains accords with the 3-fold greater concentration of androgen-receptor activity in the former. However, the size and intensity of the spot do not change when cells are preincubated for 48 hours with 3 nM methyltrienolone (MT, a non-metabolizable androgen), and it is pulse-labeled with [35S]methionine to an autoradiographically equal extent, with or without incubation in 3 nM MT for 2 or 16 hours. Furthermore, the protein identified by the spot is found in the labium majus skin fibroblast strains from 2 of 12 unrelated subjects with complete androgen resistance due to negligible androgen-receptor activity, but it is absent from those of 2 others who have the same phenotype despite a normal level of qualitatively abnormal androgen-receptor activity. Hence, it is very unlikely to be an androgen-induced protein, and it cannot be a functional version of the androgen receptor itself. Its absence in 12 of 14 labium majus strains of subjects with complete androgen resistance, regardless of 5 alpha-reductase activities, indicates that it is neither a constitutive cytotypic marker of genital skin fibroblast differentiation nor a reflection of that enzyme. When intact prepuce fibroblasts are covalently labeled by photolysis with 50 nM [3H]MT, the only specific labeling detectable after two-dimensional electrophoresis is in the 6.7 and 6.5 pI doublet of the 56 kDa protein. Considering the sensitivity of silver staining and the incomplete concordance between the androgen-receptor activity of a strain and the size/intensity of its 6.7 pI/56 kDa spot on the gels, we postulate the latter to be a comparatively abundant androgen-binding protein that is causally related to the androgen receptor. The precise nature of this relation remains to be elucidated by use of novel immunologic and/or nucleic acid probes for this protein and for the mature androgen receptor. In any event, the presence or absence of the 6.7 pI/56 kDa protein in genital skin fibroblast lysates is a new marker of genetic heterogeneity within the class of complete androgen resistance.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1988

Traumatic perforations of the esophagus.

Over the past 15 years nine patients with traumatic mechanical perforations of the esophagus have been treated. Seven perforations were iatrogenic, two were accidental. One patient treated conservatively did well. Two patients were operated on without delay. Their hospitalization was short and they had no complications. Six patients were referred to surgery after a delay ranging from 5 days to 17 days from the time of perforation. Their hospitalization ranged from 9 to 113 days, averaging 62.7 days. Complications were common and two patients died. In order to assure survival of patients with esophageal perforation, early aggressive treatment is essential in nearly all instances. In an occasional patient with a small and clean perforation at the esophageal inlet, conservative treatment may be justified.

Adolescent↗
PubMed1987

Model analysis of the bases of multistationarity in the humoral immune response.

A formal analysis of the regulation of antibody production has been developed. It comprises two complementary approaches: a logical analysis in terms of discrete (boolean) variables and functions and a more classical analysis in terms of differential equations. A first paper dealt mostly with the logical description which provided global information on how complex the network needs to be in order to account for some main aspects of the immune response, without having to specify the details of the cellular interactions or to introduce a great number of parameters. Here we present the continuous approach and, in particular, a detailed study of the steady states and a discussion of their role in the dynamics of the immune response. The model subject to this analysis is a minimal one, which takes into account a small number of well-established facts concerning lymphocyte interactions and some reasonable assumptions. The core of the model is a negative feedback loop between the helper (TH) and suppressor (TS) T lymphocytes on which autocatalytic loops of the TH and TS populations on themselves are grafted. The salient feature of this minimal scheme is the prediction, for given environmental and parametrical conditions, of a multiplicity of steady states. This multistationarity occurs both in the absence of antigen or for constant antigen levels. Variations in the external constraints provoke switches among the steady states which might be related to the various modes of the humoral immune response, and depend on the doses of antigen injected and on the previous antigenic history of the system. In particular, high and low dose paralysis appear to be associated with two distinct steady state branches.

B-Lymphocytes↗