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Biomedical subjects

J Kaufman

Publications and source records attributed to J Kaufman.

At least 73 records · Page 4Linked to original sources
PubMed1998

Evidence for a subsurface ocean on Europa.

Ground-based spectroscopy of Jupiter's moon Europa, combined with gravity data, suggests that the satellite has an icy crust roughly 150 km thick and a rocky interior. In addition, images obtained by the Voyager spacecraft revealed that Europa's surface is crossed by numerous intersecting ridges and dark bands (called lineae) and is sparsely cratered, indicating that the terrain is probably significantly younger than that of Ganymede and Callisto. It has been suggested that Europa's thin outer ice shell might be separated from the moon's silicate interior by a liquid water layer, delayed or prevented from freezing by tidal heating; in this model, the lineae could be explained by repetitive tidal deformation of the outer ice shell. However, observational confirmation of a subsurface ocean was largely frustrated by the low resolution (>2 km per pixel) of the Voyager images. Here we present high-resolution (54 m per pixel) Galileo spacecraft images of Europa, in which we find evidence for mobile 'icebergs'. The detailed morphology of the terrain strongly supports the presence of liquid water at shallow depths below the surface, either today or at some time in the past. Moreover, lower-resolution observations of much larger regions suggest that the phenomena reported here are widespread.

Extraterrestrial Environment↗
PubMed1998

Occupational dermatitis causing days away from work in U.S. private industry, 1993.

BACKGROUND: Occupational skin disease is an important cause of disability in the workplace. The aim of this report is to estimate the incidence of occupational dermatitis cases that causes days away from work and to characterize the cases. METHODS: The Annual Survey of Occupational Injuries and Illnesses from the Bureau of Labor Statistics collects employer reports on work-related dermatitis. Descriptive data are collected on a sample of the cases that result in days away from work. Estimates of the number of cases and days away from work were calculated by industry, occupation, and exposure source. RESULTS: In 1993, there were an estimated 8,835 cases of occupational dermatitis, a rate of 1.12/10,000 workers. The largest number of cases was in health services, while the highest rate was in agricultural crops. The occupation with the largest number of cases was non-construction laborers. Cleaning/polishing agents caused the largest number of cases. Calcium hydroxide and oxides caused a median of nine days away from work. DISCUSSION/CONCLUSIONS: The survey data show that the effect of occupational dermatitis is substantial in the lives of workers. These descriptive data should be used to target interventions.

Absenteeism↗
PubMed1998

3D NMR experiments for measuring 15N relaxation data of large proteins: application to the 44 kDa ectodomain of SIV gp41.

A suite of 3D NMR experiments for measuring 15N-¿1H¿ NOE, 15N T1, and 15N T1rho values in large proteins, uniformly labeled with 15N and 13C, is presented. These experiments are designed for proteins that exhibit extensive spectral overlap in the 2D 1H-15N HSQC spectrum. The pulse sequences are readily applicable to perdeuterated samples, which increases the spectral resolution and signal-to-noise ratio, thereby permitting the characterization of protein dynamics to be extended to larger protein systems. Application of the pulse sequences is demonstrated on a perdeuterated 13C/15N-labeled sample of the 44 kDa ectodomain of SIV gp41.

Carbon Isotopes↗
PubMed1998

Basic fibroblast growth factor stimulates angiogenesis in the hindlimb of hyperglycemic rats.

Angiogenic growth factors including basic fibroblast growth factor (bFGF) have therapeutic value for chronic ischemia in nondiabetic animals. However, angiogenic therapy for chronic ischemia in a background of diabetes remains unexplored. In the present study, we evaluated the effects of exogenous bFGF on angiogenesis in streptozotocin-induced diabetic rats with ischemic and nonischemic limbs. We produced ischemia of the left lower limb by excising the superficial femoral artery. At 2 weeks, the rats received an intramuscular injection of vehicle (group A), 0.3 microg bFGF/day (group B), or 1 microg bFGF/day (group C), daily for 2 weeks. At 4 weeks, we assessed limb angiogenesis by skeletal muscle capillary density (cap/mm2) and capillary per muscle fiber ratio (cap/F) counts. Group C had significantly higher mean levels compared to group A for calf capillary density (P < 0.0024) and capillary per muscle fiber ratio in both thigh (P < 0.0015) and calf (P < 0.0001). There was a trend toward increased mean capillary per muscle fiber ratio with increasing dose. This trend was significant in the calf (P < 0.0015) and just missed statistical significance in the thigh. There was a similar trend in calf capillary density. We conclude that exogenous bFGF enhances angiogenesis and, possibly, collateral circulation in ischemic limbs of diabetic rats.

Animals↗
PubMed1998

Wide tissue distribution of axolotl class II molecules occurs independently of thyroxin.

Unlike most salamanders, the Mexican axolotl (Ambystoma mexicanum) fails to produce enough thyroxin to undergo anatomical metamorphosis, although a "cryptic metamorphosis" involving a change from fetal to adult hemoglobins has been described. To understand to what extent the development of the axolotl hemopoietic system is linked to anatomical metamorphosis, we examined the appearance and thyroxin dependence of class II molecules on thymus, blood, and spleen cells, using both flow cytometry and biosynthetic labeling followed by immunoprecipitation. Class II molecules are present on B cells as early as 7 weeks after hatching, the first time analyzed. At this time, most thymocytes, all T cells, and all erythrocytes lack class II molecules, but first thymocytes at 17 weeks, then T cells at 22 weeks, and finally erythrocytes at 26-27 weeks virtually all bear class II molecules. Class II molecules and adult hemoglobin appear at roughly the same time in erythrocytes. These data are most easily explained by populations of class II-negative cells being replaced by populations of class II-positive cells, and they show that the hemopoietic system matures at a variety of times unrelated to the increase of thyroxin that drives anatomical metamorphosis. We found that administration of thyroxin during axolotl ontogeny does not accelerate or otherwise affect the acquisition of class II molecules, nor does administration of drugs that inhibit thyroxin (sodium perchlorate, thiourea, methimazole, and 1-methyl imidazole) retard or abolish this acquisition, suggesting that the programs for anatomical metamorphosis and some aspects of hemopoietic development are entirely separate.

Ambystoma↗
PubMed1998

Psychopathology in the relatives of depressed-abused children.

OBJECTIVE: To determine if the type of symptomatology abused children manifest is related to family history of psychopathology. METHOD: Lifetime history of psychopathology was assessed in the relatives of 26 preadolescents--13 depressed abused (MDD-AB) and 13 depressed nonabused (MDD-NA) children. Rates of disorder in the relatives of these children were compared to published rates of psychopathology in relatives of 27 normal control (NC) children. Data were obtained on 104 first-degree relatives (MDD-AB = 25, MDD-NA = 29, NC = 50) and 503 second-degree relatives (MDD-AB = 127, MDD-NA = 117, NC = 259). The Schedule for Affective Disorders and Schizophrenia was used to assess psychopathology in parents, and Family History method was used to obtain lifetime psychiatric data for all other relatives. RESULTS: When compared to first-degree relatives of NC children, first-degree relatives of MDD-AB children had approximately a nine-fold increased risk for major depression, and a three- to nine-fold increased risk for other disorders associated with the familial subtype of affective illness known as Depression Spectrum Disease (e.g., antisocial personality, alcohol and substance dependence). Similar findings were reported in second-degree relatives, and comparisons between the relatives of MDD-NA and NC children. CONCLUSION: The findings extend results of prior research and (1) suggest familial vulnerability factors influence the symptom profile of abused children; and (2) highlight the value of incorporating psychiatric formulations into multidisciplinary models of child abuse research and treatment programs.

Adolescent↗
PubMed1998

Males and females use different distal cues in a virtual environment navigation task.

The study of navigational ability in humans is often limited by the restricted availability and inconvenience of using large novel environments. In the present study we use a computer-generated virtual environment to study sex differences in human spatial navigation. Adult male and female participants navigated through a virtual water maze where both landmarks and room geometry were available as distal cues. Manipulation of environmental characteristics revealed that females rely predominantly on landmark information, while males more readily use both landmark and geometric information. We discuss these results as a possible link between recent human research reporting hippocampal activation in spatial tasks and animal work showing sex differences in both spatial ability and hippocampal development.

Adult↗
PubMed1997

The corticotropin-releasing hormone challenge in depressed abused, depressed nonabused, and normal control children.

Hypothalamic-pituitary-adrenal (HPA) axis disturbances in depressed children with a history of abuse were examined. Thirteen depressed abused, 13 depressed nonabused, and 13 normal control children were given 1.0 microgram/kg of human corticotropin-releasing hormone (CRH) intravenously. Blood samples for corticotropin (ACTH) and cortisol were obtained at nine intervals. When compared to depressed nonabused and normal control children, depressed abused children had significantly greater peak, total, and net ACTH secretion post-CRH. Increased ACTH secretion was only observed in depressed abused children experiencing ongoing chronic adversity (marital violence, emotional abuse, poverty, lack of supports). The pattern of findings of the depressed abused children experiencing ongoing adversity parallels the pattern of HPA axis dysregulation reported in animal studies of chronic stress. They add to a growing body of literature suggesting measures of past trauma and current adversity are important sources of variability in psychobiological correlates of major depression.

Adolescent↗
PubMed1997

Determination of the secondary structure and global topology of the 44 kDa ectodomain of gp41 of the simian immunodeficiency virus by multidimensional nuclear magnetic resonance spectroscopy.

The gp41 protein of the human (HIV) and simian (SIV) immunodeficiency viruses is part of the envelope glycoprotein complex gp41/gp120 which plays an essential role in viral infection. We present a multidimensional NMR study on the trimeric 44 kDa soluble ectodomain of SIV gp41 (e-gp41), comprising residues 27 to 149. Despite the large molecular weight and very limited spectral dispersion, complete backbone 1H, 13C, 13CO and 15N assignments have been made using a combination of triple resonance experiments on uniformly 13C/15N and 2H/13C/15N-labeled samples. The secondary structure of SIV e-gp41, derived on the basis of 13C chemical shifts, NH exchange rates, medium range nuclear Overhauser enhancements (NOE), and 3JHNalpha coupling constants, consists of a 49 residue helix at the N terminus (residues 29 to 77) and a 40 residue helix at the C terminus (residues 108 to 147), connected by a 30 residue loop which does not display any of the characteristics of regular secondary structure. The cross-peak intensities of the loop region in scalar correlation experiments suggests that it is more mobile than the core helical regions. The presence, however, of numerous long range NOEs, both intra and inter-subunit, within the loop indicates that it adopts a well-defined structure in which the loops from the three subunits interact with each other. Based on a number of long range intra and inter-subunit NOEs, a topological model is presented for the symmetric SIV e-gp41 trimer in which the N-terminal helices are packed within the protein interior in a parallel trimeric coiled-coil arrangement, while the C-terminal helices are located on the protein exterior, oriented antiparallel to the N-terminal helices.

Amino Acid Sequence↗
PubMed1997

Neuroendocrine response to 5-hydroxy-L-tryptophan in prepubertal children at high risk of major depressive disorder.

BACKGROUND: Altered serotonergic function has been observed in prepubertal children and adults with an acute episode of major depressive disorder (MDD). However, it is not known whether these alterations are present prior to the onset of MDD. METHODS: A serotonergic precursor, 5-hydroxy-L-tryptophan (L-5HTP) (oxitriptan) (0.8 mg/kg), was administered through an indwelling catheter to 36 children at high risk of MDD (with high family loading for MDD), 31 children with MDD, and 23 low-risk normal controls (with low family loading for mood disorders and no history of psychopathology). Blood samples for cortisol, prolactin (PRL), and growth hormone were obtained every 15 minutes for 180 minutes, beginning 30 minutes before L-5HTP infusion. RESULTS: Children at high risk of MDD and children with MDD had similar hormonal responses following L-5HTP infusion. After controlling for baseline values, both groups secreted significantly less cortisol and more PRL than did the low-risk normal controls, with the PRL finding being limited to girls. There were no between-group differences in baseline cortisol, PRL, or growth hormone secretion measures. CONCLUSIONS: Before the onset of affective illness, high-risk children had the same pattern of neuroendocrine response to the L-5HTP challenge as did children with MDD. These results extend earlier findings of altered serotonergic regulation in association with early-onset depression and indicate that these alterations may represent a trait marker for depression in children.

5-Hydroxytryptophan↗
PubMed1997

Injuries due to assaults on psychiatric hospital employees in Washington State.

In order to estimate rates and identify risk factors for assaults on employees of a state psychiatric hospital, we examined workers' compensation claims, hospital-recorded incident reports, and data collected in a survey of ward staff. Results revealed 13.8 workers' compensation claims due to assault per 100 employees per year. Assaults were responsible for 60% of total claims. Incident reports revealed 35 injuries due to assault per 100 employees per year. Survey data revealed 415 injuries due to assault per 100 employees per year. Of the respondents, 73% reported at least a minor injury during the past year. Assault management training in the past year was associated with less severe injuries. Working in isolation, the occupation of mental health technician, and working on the geriatric-medical hospital unit were associated with more severe injuries during the past year. Assaults on staff in psychiatric hospitals represent a significant and underrecognized occupational hazard.

Analysis of Variance↗
PubMed1997

Falls in construction: injury rates for OSHA-inspected employers before and after citation for violating the Washington State Fall Protection Standard.

This study examined the relationship between Washington's fall protection standard and injuries in construction workers. Workers' compensation claim rates for falls were examined for employers that were cited for violating the standard over the 1991-1992 period. Fall injury rates for the periods before and after inspections were compared. Claims for a control group of employers that had not been cited were also examined. For the 784 cited employers, the claim rate for compensable fall injuries decreased from 1.78 to 1.39 per 200,000 hours worked for the one-year periods before and after inspection. For the control group (n = 8,301), the claim rate decreased from 1.04 to 0.95 per 200,000 hours. Cited employers were 2.3 times as likely as control employers (p < 0.0001) to experience a claim rate reduction, after adjustment for employer size and type of business. Results suggested that industry-wide fall injury rates might be expected to decrease if more employers were inspected.

Accidental Falls↗
PubMed1997

Refined solution structure and backbone dynamics of HIV-1 Nef.

The tendency of HIV-1 Nef to form aggregates in solution, particularly at pH values below 8, together with its large fraction of highly mobile residues seriously complicated determination of its three-dimensional structure, both for heteronuclear solution NMR (Grzesiek et al., 1996a, Nat Struct Biol 3:340-345) and for X-ray crystallography (Lee et al., 1996, Cell 85:931-942). Methods used to determine the Nef structure by NMR at pH 8 and 0.6 mM concentration are presented, together with a detailed description of Nef's secondary and tertiary structure. The described techniques have general applicability for the NMR structure determination of proteins that are aggregating and/or have limited stability at low pH values. Extensive chemical shift assignments are reported for backbone and side chain 1H, 13C, and 15N resonances of the HIV-1 Nef deletion mutants NEF delta 2-39, NEF delta 2-39, delta 159-173, and of NEF delta 2-39, delta 159-173 in complex with the SH3 domain of the Hck tyrosine protein kinase. Besides a type II polyproline helix, Nef's structure consists of three alpha-helices, a 3(10) helix, and a five-stranded anti-parallel beta-sheet. The analysis of 15N relaxation parameters of the backbone amide sites reveals that all the secondary structure elements are non-mobile on the picosecond to nanosecond and on the millisecond time scale. A large number of slowly exchanging amide protons provides evidence for the stability of the Nef core even on the time scale of hours. Significant internal motions on the ps to ns time scale are detected for residues 60 to 71 and for residues 149 to 180, which form solvent-exposed loops. The residues of the HIV-1 protease cleavage site (W57/L58) do not exhibit large amplitude motions on the sub-nanosecond time scale, and their side chains insert themselves into a hydrophobic crevice formed between the C-terminus of helix 1 and the N-terminus of helix 2. A refined structure has been determined based on additional constraints for side-chain and backbone dihedral angles derived from a large number of three-bond J-coupling and ROE data.

Amides↗