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Biomedical subjects

B Tobias

Publications and source records attributed to B Tobias.

At least 19 recordsLinked to original sources
PubMed2001

Occupational health surveillance strategies for an ethnically diverse Asian employee population.

1. Implementation of a medical/health surveillance program can prevent the damaging effects of lead toxicity. Lead toxicity may be a result of acute or chronic exposure and can affect the hematopoietic, nervous, renal, and reproductive systems. 2. Minority groups tend to be overrepresented in lead industries. Further, an increase in high lead levels can be compounded by cultural influences. Education must be geared toward the specific employee populations. 3. Successful programs require assistance from all team members--occupational health nurse, safety engineer, industrial hygienist, and environmental engineer. Occupational health nurses play an important role in implementation of medical/health surveillance programs by scheduling regular blood testing, monitoring results, and educating employees.

Asia↗
PubMed1997

Structure-activity relationships in a series of orally active gamma-hydroxy butenolide endothelin antagonists.

The design of potent and selective non-peptide antagonists of endothelin-1 (ET-1) and its related isopeptides are important tools defining the role of ET in human diseases. In this report we will describe the detailed structure-activity relationship (SAR) studies that led to the discovery of a potent series of butenolide ETA selective antagonists. Starting from a micromolar screening hit, PD012527, use of Topliss decision tree analysis led to the discovery of the nanomolar ET(A) selective antagonist PD155080. Further structural modifications around the butenolide ring led directly to the subnanomolar ETA selective antagonist PD156707, IC50's = 0.3 (ET(A)) and 780 nM (ET(B)). This series of compounds exhibited functional activity exemplified by PD156707. This derivative inhibited the ETA receptor mediated release of arachidonic acid from rabbit renal artery vascular smooth muscle cells with an IC50 = 1.1 nM and also inhibited the ET-1 induced contraction of rabbit femoral artery rings (ETA mediated) with a pA2 = 7.6. PD156707 also displayed in vivo functional activity inhibiting the hemodynamic responses due to exogenous administration of ET-1 in rats in a dose dependent fashion. Evidence for the pH dependence of the open and closed tautomerization forms of PD156707 was demonstrated by an NMR study. X-ray crystallographic analysis of the closed butenolide form of PD156707 shows the benzylic group located on the same side of the butenolide ring as the gamma-hydroxyl and the remaining two phenyl groups on the butenolide ring essentially orthogonal to the butenolide ring. Pharmacokinetic parameters for PD156707 in dogs are also presented.

Administration, Oral↗
PubMed1996

Development of a health education booklet to enhance adherence to tuberculosis treatment.

Effective anti-tuberculosis chemotherapy was developed during the 1950's, yet four decades later the cure rates for tuberculosis (TB) worldwide remain unacceptably low. A major reason for the failure to eliminate TB is that many patients with active disease fail to take sufficient anti-tuberculosis medication to render a cure. This paper describes a project designed to involve clinic nurses in the process of exploring how TB patients experience their disease. Information obtained from the qualitative research process was used to develop a photonovel which can be used to supplement the education given to newly diagnosed TB patients.

Health Education↗
PubMed1992

Natural abundance 15N NMR assignments delineate structural differences between intact and reactive-site hydrolyzed Cucurbita maxima trypsin inhibitor III.

15N NMR assignments were made to the backbone amide nitrogen atoms at natural isotopic abundance of intact and reactive-site (Arg5-Ile6) hydrolyzed Cucurbita maxima trypsin inhibitor III (CMTI-III and CMTI-III*, respectively) by means of 2D proton-detected heteronuclear single bond chemical shift correlation (HSBC) spectroscopy, utilizing the previously made sequence-specific 1H NMR assignments (Krishnamoorthi et al. (1992) Biochemistry 31, 898-904). Comparison of the 15N chemical shifts of the two forms of the inhibitor molecule revealed significant changes not only for residues located near the reactive-site region, but also for those distantly located. Residues Cys3, Arg5, Leu7, Met8, Cys10, Cys16, Glu19, His25, Tyr27, Cys28 and Gly29 showed significant chemical shift changes ranging from 0.3 to 6.1 ppm, thus indicating structural perturbations that were transmitted throughout the molecule. These findings confirm the earlier conclusions based on 1H NMR investigations.

Amino Acid Sequence↗
PubMed1991

Detection and identification of endogenous small molecules in ocular tissues by proton nuclear magnetic resonance spectroscopy.

Proton nuclear magnetic resonance (nmr) spectra of rabbit ocular tissue homogenates (corneal epithelium, conjunctiva and iris ciliary body) and aqueous humor have been recorded for the first time by incorporation of a spin-spin relaxation reagent and use of the CPMG pulse sequence. A number of endogenous species such as lactate, glucose, alanine and valine have been observed in these ocular homogenates and significant differences have been noted in the distribution of these small molecules in the ocular tissues studied. This technique has been used to study the hydrolysis of acetylcholine by ocular esterases in the iris ciliary body.

Amino Acids↗
PubMed1990

Dental screening of long stay geriatric patients in West Essex and recommendations for their care.

A dental screening programme at a West Essex Health Authority hospital provided data from 151 in-patients, most of whom were in long-stay geriatric care. 71 per cent were female and the mean age of the geriatric patients was 81 years. 61 subjects (40 per cent) suffered predominantly from mental illness. 107 subjects (71 per cent) were edentulous but a higher proportion of elderly mentally ill patients (42 per cent) had retained some of their natural teeth compared with 20 per cent of the others. 26 edentulous subjects were not in possession of any dentures and the standard of oral and denture hygiene was poor. 59 in-patients (39 per cent) had 'expressed' need for dental treatment and a further 51 (34 per cent) were unable or unwilling to communicate their need. An important aspect of their dental care was the provision and maintenance of a preventive dental programme for both dentate patients and denture wearers.

Aged↗
PubMed1988

Dental aspects of an elderly population.

A study of 414 elderly residents of sheltered accommodation in West Essex investigated the degree to which health, physical handicap and support from community care services affected dental needs and utilization of dental services. The study population had a mean age of 77 years, 77% lived alone, 17% were housebound and 37% relied heavily on the home help service. The majority of subjects were edentulous (78%) and prosthetic treatment was the main requirement. Despite the high normative need for dental treatment (75%), only 22% of subjects perceived any such need. Only 3% claimed to have any difficulties in obtaining dental treatment and utilization of dental services was associated with positive attitudes towards dental health. The presence of oral handicaps was a realistic indicator of treatment needs and could be identified by the primary health team.

Aged↗
PubMed1982

20 alpha-Hydroxysteroid dehydrogenase and 17 beta-estradiol dehydrogenase localize in cytosol of human term placenta.

The 20 alpha-hydroxysteroid dehydrogenase activity in human term placenta has been localized by different investigators to nuclear, mitochondrial, microsomal, and cytosolic subcellular fractions. Furthermore, in the cytosol, 20 alpha-hydroxysteroid dehydrogenase activity may be a second function of the enzyme that mediates 17 beta-estradiol dehydrogenase activity. To search for a unique 20 alpha-hydroxysteroid dehydrogenase, human placental villous tissue, homogenized in three different buffer systems, was fractionated by differential centrifugation, and the 17 beta- and 20 alpha-activities were measured by radioisotope conversion assay. The enrichment and purity of the subcellular fractions were shown by marker enzyme assays and electron microscopy studies. Under all experimental conditions, 20 alpha-hydroxysteroid dehydrogenase activity was identified only in the 105,000 g placental cytosol: intact, osmotically ruptured, and acetone-extracted mitochondria, nuclei, and microsomes did not convert progesterone to 20 alpha-dihydroprogesterone. Furthermore, because 17 beta-estradiol dehydrogenase activity was in large part soluble in the cytosol, these localization studies are consistent with the hypothesis that the 20 alpha- and 17 beta-oxidoreductase activities in human placenta reside on one soluble protein.

17-Hydroxysteroid Dehydrogenases↗
PubMed1981

Affinity labeling of human placental 17 beta-estradiol dehydrogenase and 20 alpha-hydroxysteroid dehydrogenase with 5'-[p-(fluorosulfonyl)benzoyl]adenosine.

Two pyridine nucleotide linked oxidoreductase activities, 17 beta-estradiol dehydrogenase and 20 alpha-hydroxysteroid dehydrogenase, which were copurified from human placental cytosol as a homogeneous enzyme preparation, may represent dual activity by one enzyme. The affinity labeling nucleotide analogue 5'-[p-(fluorosulfonyl)benzoyl]adenosine, which binds at the cofactor site as a competitive inhibitor of NADH (ki = 1.7 mM), simultaneously and identically inactivated both the 17 beta and 20 alpha activities in a time-dependent and irreversible manner following pseudo-first-order kinetics. NADH and NAD+ markedly protected both activities from inactivation, and the substrate steroids, estrone, estradiol, progesterone, and 20 alpha-hydroxy-4-pregnen-3-one, conferred similar protection, though less than cofactor, against simultaneous loss of both activities. Stoichiometric studies indicated that 2 mol of affinity labeling nucleotide were bound per mol of completely inactivated enzyme dimer. The coincident and identical loss of both activities under all experimental conditions is further evidence that 17 beta-estradiol dehydrogenase and 20 alpha-hydrosteroid dehydrogenase in human placental cytosol represent bifunctional, stereospecific, oxidoreductase activity at one active site on a single protein.

17-Hydroxysteroid Dehydrogenases↗
PubMed1981

Human placental 17 beta-estradiol dehydrogenase and 20 alpha-hydroxysteroid dehydrogenase. Two activities at a single enzyme active site.

Two soluble enzyme activities, 17 beta-estradiol dehydrogenase and 20 alpha-hydroxysteroid dehydrogenase, present in the cytosol fraction of term human placenta, were co-purified with a constant ratio of specific activities, approximating 100:1, respectively. The "pure enzyme" is a single band on sodium dodecyl sulfate disc gel electrophoresis. To evaluate whether catalysis of the estrogen and progestin substrates occurs at a single active site, alkylation studies using 16 alpha-bromoacetoxyprogesterone were designed. This affinity alkylating steroid binds at the enzyme-active site (km 256 microM; Vmax = 0.012 mumol/min/mg), inactivates the enzyme in an irreversible and time-dependent manner which follows pseudo-first order kinetics, and causes coincident loss of both the 17 beta- and 20 alpha-activities. Affinity radioalkylation studies using 16 alpha-[2'-3H]bromoacetoxyprogesterone indicate that 2 mol of steroid bind per mol of inactivated enzyme dimer (Mr = 68,000). Amino acid analyses of the acid hydrolysate of radioalkylated enzyme show that 16 alpha-bromoacetoxyprogesterone dicarboxymethylates a histidyl residue in the active site. These results are identical with those reported for 16 alpha-[2'-3H]bromoacetoxyestradiol 3-methyl ether inactivation and radioalkylation of identically purified "17 beta-estradiol dehydrogenase." Computer graphics were used to construct a model in which: 1) binding of estrogen and progestin substrates at one active site permits stereospecific catalysis; 2) the estrogen and progestin analogs' alkylating side arms have access to a common histidine residue. These observations clearly demonstrate that the catalysis of estrogen and progestin substrates can occur at a single active site of one enzyme.

17-Hydroxysteroid Dehydrogenases↗
PubMed1981

Photoactivated zinc silicate in thin layer chromatography plates: a potential cause for error in liquid scintillation counting.

Thin layer chromatography plates impregnated with fluorescent indicator permit easy identification of many compounds by exposure to ultraviolet light. Exposure of zinc silicate treated plates to ultraviolet light (254 nm) for 30 seconds induced photoluminescence which persisted at significant levels for longer than 24 hours. This artifact significantly interfered with radioactivity quantitation in three commercially available liquid scintillation solutions. Chromatography plates impregnated with calcium silicate demonstrated insignificant ultraviolet light induced photoluminescence. The use of 14C rather than 3H-radiolabeled compounds, protecting the plate with aluminum foil when visualizing reference compounds with ultraviolet light, and heating the photoactivated plate to accelerate disappearance of the photoluminescence minimized the error in liquid scintillation counting.

20-Hydroxysteroid Dehydrogenases↗
PubMed1981

Study of human placental estradiol-17 beta dehydrogenase/20 alpha-hydroxysteroid dehydrogenase by preparative disc-gel electrophoresis.

The soluble enzyme, estradiol-17 beta dehydrogenase from human term placenta, appears to co-purify with a second soluble enzyme, 20 alpha-hydroxysteroid dehydrogenase. The enzyme, which had been partially purified by affinity chromatography, fractionated on a preparative electrophoresis gel to a homogeneous preparation containing both estradiol-17 beta dehydrogenase and 20 alpha-hydroxysteroid dehydrogenase activities in a ratio of approximately 100:1. Analytical polyacrylamide disc-gels resolved this homogeneous preparation as a single band by both protein and activity staining techniques. Homogeneous enzyme inactivated and affinity-radioalkylated by 16 alpha-[2'-14C]bromoacetoxyprogesterone or 16 alpha-[2'-14C] bromoacetoxyestradiol 3-methyl ether, and when analyzed by SDS disc-gel electrophoresis, gave a single protein band which corresponded identically to the radioactivity peaks. These observations support the hypothesis that estradiol-17 beta dehydrogenase and 20 alpha-hydroxysteroid dehydrogenase represent dual oxidoreductase activity in one enzyme. Preparative disc-gel electrophoresis, a technique which has not been previously adapted to purification of these human placental enzyme activities, was useful to rapidly (3 days) effect a 15-fold enrichment of the estradiol-17 beta dehydrogenase specific activity from "heat-treated cytosol". Thus, laboratory-scale preparative disc-gel electrophoresis is useful for rapid, small-scale enrichment of this soluble enzyme.

17-Hydroxysteroid Dehydrogenases↗
PubMed1980

Study of 3 alpha, 20 beta-hydroxysteroid dehydrogenase with an enzyme-generated affinity alkylator: dual enzyme activity at a single active site.

The substrate 17 beta-[(1S)-1-hydroxy-2-propynyl]-androst-4-en-3-one (beta-HPA) and its enzyme-generated alkylating product 17 beta-(1-oxo-2-propynyl)androst-4-en-3-one (OPA) were synthesized to investigate the relationship between the 3 alpha and 20 beta activities observed in commercially available cortisone reductase (EC 1.1.1.53) from Streptomyces hydrogenans. beta-HPA, a substrate [apparent Km = 145 microM; Vmax = 63 nmol (min microgram)-1], when enzymatically oxidized by cortisone reductase of OPA, inactivates simultaneously the 3 alpha and 20 beta activities in a time-dependent and irreversible manner following pseudo-first-order kinetics. OPA alone, an affinity alkylating steroid (KI = 40.5 microM; k3 = 1.8 X 10(-2) S-1), simultaneously inactivates 3 alpha and 20 beta activities in a time-dependent and irreversible manner. At pH 7, the t 1/2 of enzyme inactivation for beta-HPA (10 h) or OPA (41 min) is slower than at pH 9.2 (beta-HPA, 16 min, and OPA, 3.3 min). Substrates (progesterone, 20 beta-hydroxypregn-4-en-3-one, and 5 alpha-dihydrotestosterone), but not all steroids (20 al]ha-delta 4-pregn-4-en-3-one and 17 beta-estradiol), protect against loss of both enzyme activities by beta-HPA and OPA. The alpha isomer of HPA is not enzymatically oxidized and therefore does not cause inactivation of either 3 alpha or 20 alpha activity. Thus, beta-HPA functions as a substrate for the enzymatic generation of a powerful affinity alkylator of cortisone reductase. Second, the identical change in both the 3 alpha and 20 beta activities in all experimental conditions clearly results from dual enzyme activity at a single enzyme active site.

20-Hydroxysteroid Dehydrogenases↗
PubMed1980

Estradiol 17 beta-dehydrogenase and 20 alpha-hydroxysteroid dehydrogenase from human placental cytosol: one enzyme with two activities?

The soluble enzyme estradiol 17 beta-dehydrogenase (17 beta-ED) from human term placental cytosol is reported to be a stereospecific oxidoreductase for estrogen substrates. A published purification scheme (heat treatment and affinity chromatography) yielded a homogeneous protein which had the reported characteristics of pure 17 beta-ED and also had 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) activity. Spectrophotometric assay when the buffer contained albumin, 8 mg/ml, masked the 20 alpha-HSD activity observed in albumin-free conditions and may explain why this bifunctional activity has gone unrecognized. In human placenta, one enzyme may catalyze stereospecific oxidation/reduction of both estrogen and progesterone.

17-Hydroxysteroid Dehydrogenases↗
PubMed1978

[Arterial pressure changes during exertion in the normal subject].

The exercice electrocardiogram, carried out in 160 normal subjects, has allowed us to witness the physiological mechanisms of adaptation to exercise as a function of age and sex. The relationship between systolic arterial pressure (SAP) and cardiac rate (CR) is very narrow (R = 0.97), and is a linear function. Its slope increases with age in both sexes, and differs significantly in the male and female (P less than 0.001). Systolic pressure is related to the relative cardiac rate (CR%) by the formula SAP = 1.55.CR% + 70.

Adaptation, Physiological↗