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Biomedical subjects

M Kaufman

Publications and source records attributed to M Kaufman.

At least 91 records · Page 5Linked to original sources
PubMed1991

Strain differences in mouse brain weight gain and spatial-location scores during postnatal development.

Brain weight and performance on a spatial-location test were measured from birth to weaning on mouse strains CD1, Balb/c, and their F1 cross. For CD1, onsets of both the last rapid-brain-growth stage and nonzero scores on the spatial-location test were around age 17 days; asymptotes of both were reached about age 23 days. Balb/c and F1 had at least 5- to 6-day delays of both onsets and asymptotes. For the strains studied, onset of nonzero performance on the spatial-location test may be a provisional indicator of onset of significant and rapid brain growth after age 15 days. The delayed F1 brain growth stage could indicate that control of brain growth about age 20 days resides in an inhibitory factor present in Balb/c but not in CD1.

Animals↗
PubMed1991

Substitution of aspartic acid-686 by histidine or asparagine in the human androgen receptor leads to a functionally inactive protein with altered hormone-binding characteristics.

We have identified two different single nucleotide alterations in codon 686 (GAC; aspartic acid) in exon 4 of the human androgen receptor gene in three unrelated families with the complete form of androgen insensitivity. One mutation (G----C) results in an aspartic acid----histidine substitution (with 15-20% of wild-type androgen-binding capacity), whereas the other mutation (G----A) leads to an aspartic acid----asparagine substitution (with normal androgen-binding capacity, but a rapidly dissociating ligand-receptor complex). The mutations eliminate a Hinfl restriction site. Screening for the loss of the Hinfl site in both families with the Asp----Asn mutation resulted in the recognition of heterozygous carriers in successive generations of each. Both mutant androgen receptors were generated in vitro and transiently expressed in COS and HeLa cells. The receptor proteins produced had the same altered binding characteristics as those measured in fibroblasts from the affected subjects. R1881-activated transcription of a GRE-tk-CAT reporter gene construct was strongly diminished by both mutant receptors and was only partially restored using a 100-fold higher concentration of ligand compared with wild-type receptor. Thus, aspartic acid-686 appears essential for normal androgen receptor function. Substitution of this amino acid residue, by either histidine or asparagine, results in androgen insensitivity and lack of androgen-dependent male sexual differentiation.

Adult↗
PubMed1991

Post-Tarasoff legal developments and the mental health literature.

Since Tarasoff first established the duty of psychotherapists to warn or otherwise protect third parties when a patient is considered dangerous, the mental health literature has continued to address the two most controversial issues in that case: the questionable ability of clinicians to predict violent behavior, and the role of confidentiality in psychotherapy. The author examines recent trends in the law in light of this research and concludes that so-called anti-Tarasoff statutes recently passed by some states appropriately take into account the mental health literature and effectively balance competing public policy concerns.

Confidentiality↗
PubMed1991

Acute pseudo-obstruction of the colon.

Fourteen patients with acute pseudo-obstruction of the colon (Ogilvie's syndrome) were treated over a 16-year period. Ten patients (71.4%) had a recent history of mental illness and were treated with hypnotic and sedative drugs uninterruptedly for many months. The clinical picture and abdominal radiographs on admission to hospital were typical of acute mechanical obstruction of the colon; 1 patient had a perforation of the transverse colon. Obstruction was ruled out by barium enema in 9 patients, by colonoscopy in 3 and by immediate laparotomy in 2. Twelve patients were treated conservatively by nasogastric tube, correction of fluid and electrolyte imbalance, enemas, cessation of all hypnotic and sedative drugs, and decompression of the colon using a rigid rectoscope and rectal tube. There were no complications and no deaths. Ogilvie's syndrome should be suspected in patients with symptoms of large-bowel obstruction whose history discloses intake of hypnotic and sedative drugs. After mechanical obstruction is ruled out, conservative management is indicated. It should include cessation of all psychopharmacological agents and decompression of the colon by rectal intubation or colonoscopy. If conservative measures fail and the caecum increases in size, operative decompression by transverse colostomy rather than cecostomy is indicated.

Acute Disease↗
PubMed1990

The state transitions of normal and mutant androgen-receptor complexes in human genital skin fibroblasts.

We have incubated cells from controls and subjects with receptor-defective androgen resistance with 3H-labelled testosterone (T), methyltrienolone (MT), dihydrotestosterone (DHT) or mibolerone (MB) and studied the temperature dependence of the dissociation rate constants of these various androgen-receptor (A-R) complexes both within cells and after they were extracted from them. In control cells, Arrhenius plots for T-, MT-, DHT- and MB-R complexes were linear and formed a hierarchy of dissociation states with energies of state IV greater than III greater than II, greater than I, respectively. Relative to this hierarchy, the dissociation states of the MB-, DHT- and MT-R complexes in mutant cells were displaced to higher, androgen-inappropriate energies in a mutant-distinctive pattern. When extracted from cells control or mutant T- or MT-R complexes, and mutant (but not control) DHT- or MB-R complexes lowered their respective dissociation rates by undergoing state transitions in conformity with the hierarchy. Hence we propose that different A-R complexes reach different dissociative states by undergoing sequential transitions along a common pathway, and that these transitions are co-regulated both by the chemical characteristics of the bound androgen and by other cellular non-receptor factors.

Cells, Cultured↗
PubMed1990

The 56 kDa androgen-binding protein in human genital skin fibroblasts: its relation to the human androgen receptor.

We have recently described in genital skin fibroblasts (GSF) a relatively abundant 56 kDa protein with androgen-binding activity. This protein is missing in GSF of most patients with complete androgen insensitivity syndrome (CAI). The protein has many characteristics compatible with the androgen receptor; it has in fact been tentatively considered as a precursor or degradation form of the prototypic (approximately 100 kDa) human androgen receptor. We have prepared an antiserum to this protein, which allowed us to detect it as a direct product by in vitro translation of mRNA from GSF. It is thus very unlikely to be a degradation product of a larger precursor. Furthermore, covalent photolytic labeling of this protein with the androgen analogue [3H]mibolerone revealed a much lower affinity for this protein than is known for the androgen receptor. Finally, the GSF of two exceptional patients with complete androgen insensitivity syndrome due to negligible androgen receptor-binding activity express this protein normally, as determined on two-dimensional gels by Western blot analysis with the antiserum and by photolytic covalent labeling with androgen analogues. These data indicate that the protein is not a precursor or a degradation product of the receptor; nor is it androgen-induced. They are more compatible with the idea that the protein is another member of the steroid/thyroid/retinoic acid receptor supergene family, perhaps as an unorthodox product of the human androgen receptor gene.

Androgen-Binding Protein↗
PubMed1990

Diagnosis of delayed cerebral radiation necrosis following proton beam therapy.

A 27-year-old man developed delayed cerebral radiation necrosis following proton beam therapy to an arteriovenous malformation. Neuroimaging with technetium 99m diethylenetriamine penta-acetic acid and positron emission tomographic scanning with fludeoxyglucose F 18 aided in his evaluation. Significant improvement of his neurologic deficits resulted from corticosteroid therapy. Clinical resolution was corroborated by serial computed tomographic scans demonstrating regression of the abnormality (a mass lesion). Various facets of radiation injury are discussed, including pathogenesis, risk factors, diagnosis, and therapy.

Adult↗
PubMed1990

Androgen receptor defects in patients with minimal and partial androgen resistance classified according to a model of androgen-receptor complex energy states.

We have characterized intracellularly the androgen-receptor (A-R) complexes formed by genital skin fibroblasts from 2 unrelated males with qualitative defects of the androgen receptor: one has a small nonhypospadic penis as part of a syndrome of mild androgen resistance; the other was born with ambiguous external genitalia. The dissociation rate constants of testosterone, methyltrienolone (MT), dihydrotestosterone (DHT) and mibolerone (MB) from normal androgen receptors were determined at various temperatures: when plotted by the method of Arrhenius, they yielded a linear hierarchy of dissociation states with energies of state IV greater than III greater than II greater than I, respectively. Relative to this hierarchy, patient A-R complexes were displaced to higher, androgen-inappropriate energies in a mutant-distinctive pattern. MB- or MT-R complexes of both patients were thermolabile; however, both up-regulated normally in response to prolonged incubation with either hormone. Apparent equilibrium affinity constants (Kd) of the DHT- and MB-R complexes formed by both patients were normal; however, the binding capacity (Bmax) for MB in 1 case was subnormal. The distinctive biochemical phenotypes of A-R complexes in these 2 patients with androgen resistance will facilitate the definition of structure-function relations in the androgen receptor, a classical DNA-binding, transcription-regulating protein.

Adolescent↗
PubMed1990

Capacity of state health agencies to meet nutrition objectives in maternal and child health.

Public health nutritionists in 54 official state health agencies were surveyed in 1987 to determine to what extent they were prepared to implement the Model State Nutrition Objectives developed by the Association of State and Territorial Public Health Nutrition Directors. Objectives related to services to the maternal and child health (MCH) population were the focus of one part of the survey. One half of all states have plans for nutrition services integrated into their state MCH plans. More than 75% of state agencies collect data on the nutritional status of pregnant and lactating women, infants, and preschool children. Fewer than half collect data on dietary intake patterns or nutrition knowledge. Thirty-one agencies reported a formal quality assurance program for one or more subsets of the MCH population. At least 75% of all states provide dietary intake recommendations, screening and assessment protocols, and policies concerning referrals to maternal and infant health programs. State health agencies are already involved in activities that will facilitate adoption of the model state nutrition objectives.

Adult↗
PubMed1990

Age at death: a three hospital urban, suburban, and small town study.

Comparison of the ages of patients dying at three interrelated St. Louis hospitals in 1988 has been used to study the results of similar high-quality acute hospital care when provided to dissimilar populations. The data presented by the authors leads them to conclude that in this era of mounting health costs, we have not, at least as recently as 1988, realized that an ounce of prevention if worth a pound of cure.

Adult↗
PubMed1990

Technical aids in surgery. Two muscle-sparing thoracotomies--techniques and indications.

Two types of muscle-sparing thoracotomies are described. They have been used over the past 11 years in 396 patients. These incisions are ideal for wedge resections, biopsies, exploratory thoracotomies, excisions of emphysematous blebs, decortications, and a variety of other operations, including pulmonary resections in selected patients. They provide entirely adequate exposure, while minimising the trauma of thoracotomy.

Humans↗
PubMed1990

An exonic point mutation of the androgen receptor gene in a family with complete androgen insensitivity.

We have discovered in the X-linked androgen receptor gene a single exonic nucleotide substitution that causes complete androgen insensitivity (resistance) in a sibship with three affected individuals. The mutation, a guanine-to-adenine transition, occurs at nucleotide number 2682 and changes the sense of codon 717 from tryptophan to a translation stop signal. Codon 717 is in exon 4, so the mutation predicts the synthesis of a truncated receptor that lacks most of its androgen-binding domain. The substitution abolishes a recognition sequence for the restriction endonuclease HaeIII. Amplification of exon 4 by the polymerase chain reaction followed by double digestion with HinfI and HaeIII permits facile recognition of hemizygotes and heterozygous carriers of the mutation.

Amino Acid Sequence↗
PubMed1990

Cholecystostomy as a definitive operation.

Cholecystostomy for decompression and drainage of the biliary tree is indicated when the elderly, poor risk patient with destructive inflammatory process in the gallbladder is unable to tolerate a more extensive operation. Cholecystostomy is often criticized as an inferior operation, because it provides some palliation but leaves the patient with most problems unattended. To re-evaluate the role of cholecystostomy in the management of acute disease of the gallbladder, we reviewed our experience with it. During the years 1974 to 1987, 37 patients underwent a cholecystostomy. Patients ranged in age from 58 to 90 years, with an average age of 69 years. Twenty-eight patients had acute destructive cholecystitis, usually complicated by perforation, peritonitis or ascending cholangitis. Five had severe pancreatitis; three, cholelithiasis, and one patient, carcinoma of the bladder. Twenty-seven of the 37 patients had severe systemic disease and were critically ill. At the operation, calculi were extracted and the gallbladder and abscess were drained. Two patients died, yielding a mortality rate of 5.4 per cent. Tube cholangiography was done in 33 patients. Although residual stones were demonstrated in seven patients, the stones were removed electively at a later date under much more favorable conditions. None of the 35 survivors had symptoms of disease of the gallbladder during the follow-up period, which ranged from one to 12 years. Cholecystostomy is a curative operation indicated in critically ill and elderly patients for whom extensive operation is a prohibitive risk.

Acute Disease↗