Search PubMed⌕ Search

Biomedical subjects

J Hall

Publications and source records attributed to J Hall.

At least 361 records · Page 20Linked to original sources
PubMed1989

Effects of chlorinated benzenes on diatom fatty acid composition and quantitative morphology. II. 1,3,5-Trichlorobenzene.

Cells of the diatom Cyclotella meneghiniana were exposed in a closed system to 0.245 ppm 1,3,5-trichlorobenzene. Response of the diatom was measured by quantitative ultrastructure and fatty acid percent composition over a 5-day period. During that time, 28 significant morphological and 13 significant fatty acid percent composition changes occurred. Autophagic-like vacuoles were observed consistently through the sampling periods. In comparison with exposure to 1,2,4-trichlorobenzene, 1,3,5-trichlorobenzene exerts fewer effects in the parameters studied, and these effects were observed most frequently in membranous components during the initial eight hours of exposure. It is suggested that the amount of cellular lipid and the relative reactivity of the isomer are responsible for the observed effects.

Chlorobenzenes↗
PubMed1989

Effects of chlorinated benzenes on diatom fatty acid composition and quantitative morphology. III. 1,2,3-Trichlorobenzene.

Cells of the diatom Cyclotella meneghiniana were exposed in a closed system to 0.245 ppm 1,2,3-trichlorobenzene. Response of the diatom was measured by quantitative ultrastructure and fatty acid percent composition over a 5-day period. During that time, 35 significant morphological and 12 fatty acid percent composition changes occurred. The most pronounced morphological change that occurred was a significant increase in lipid volume. In addition, changes were observed in vacuolar relative volume, suggesting that the tonoplast became more permeable. Fewer significant changes were observed in fatty acid percent composition upon exposure to this isomer. However, there was a consistent increase in oleic acid (C18:1). The observed changes in morphological and fatty acid percent composition were uniformly distributed with time after the first hour of exposure. Results support the hypothesis that increased lipid stores may alter the timing of response to lipophilic toxicants.

Chlorobenzenes↗
PubMed1989

Effects of chlorinated benzenes on diatom fatty acid composition and quantitative morphology. IV. Pentachlorobenzene and comparison with trichlorobenzene isomers.

Cells of the diatom Cyclotella meneghiniana were exposed in a closed system to 0.095 ppm pentachlorobenzene over a period of 5 days. Changes in fatty acid and morphological percent composition were monitored to determine the effect of the toxicant. The greatest morphological change observed was an increase in lipid volume. Most morphological changes occurred in the 1 hour and 5 day sampling periods. Few changes in morphological characteristics or fatty acid percent composition were observed at eight hours, when the cells were in the dark. The C18:1 and C20:5 fatty acids were most variable with exposure to pentachlorobenzene. Results suggest that at sublethal doses, lipophilic toxicants exert effects that are biphasic. That is, immediately measurable effects are observed in the cells that include increases in storage products and changes in membranous organelles. Long-term effects are postulated to be the result of mobilization of lipophilic toxicants that have partitioned into lipid stores and are more available when lipids are metabolized. Although pentachlorobenzene has a higher octanol/water partition coefficient, it appears to exert fewer cellular changes than any trichlorobenzene isomer.

Chlorobenzenes↗
PubMed1989

The management of oesophageal carcinoma: radiotherapy or surgery? Cost considerations.

A cost comparison has been made between two treatment modalities used with curative intent for carcinoma of the oesophagus, for 144 patients seen between December 1979 and December 1985. Forty-two patients were selected for radical oesophagectomy. In this paper these are compared with 50 patients who underwent radical radiotherapy. The median survival of both groups was identical (12 months). The remaining 52 patients underwent a variety of palliative procedures and are not considered further. Components of management were identified and costed on the basis of direct resource use by the hospital. Surgically treated patients on average cost $A13,638 in 1987 dollars, whereas those treated by radiotherapy cost $A3533. The major factors accounting for this cost difference were the necessary perioperative intensive management in the surgical group, the inevitable perioperative complications and the subsequent prolonged hospitalization of a proportion of patients. The cost of the management of the complications of radiation therapy are included but were not a major factor in overall costs for the irradiated group. This cost differential must influence the continuation of current strategies in which radical surgery, rather than irradiation, is the selected routine curative approach for oesophageal cancer particularly in the absence of evidence of higher survival.

Adenocarcinoma↗
PubMed1989

Clinical economics education in the International Clinical Epidemiology Network. INCLEN Economics Faculty.

The application of rigorous epidemiologic methods to clinical questions has broadened the scope of research in epidemiology and enhanced the quality of clinical research. The International Clinical Epidemiology Network (INCLEN) has enabled physicians from developing countries to obtain training in epidemiologic methods and to provide leadership in clinical epidemiology in their home schools of medicine. The INCLEN program has recently incorporated another major theme of research training, clinical economics, which introduces research related to the effective use of limited resources. This article describes the rationale for the development of the INCLEN Clinical Economics program, outlines its organization and curriculum, and explores the challenges to its successful implementation.

Cost-Benefit Analysis↗
PubMed1989

Sulconazole nitrate 1% cream in the treatment of chronic moccasin-type tinea pedis caused by Trichophyton rubrum.

Sulconazole nitrate 1% cream applied twice daily was compared with its vehicle in the treatment of 229 patients with chronic moccasin-type tinea pedis confirmed by positive results of a potassium hydroxide preparation. At admission in this randomized, double-blind, parallel multicenter trial, 131 patients had positive dermatophyte cultures; Trichophyton rubrum was identified in 121 (92%). After 4 weeks of treatment, patients were examined and, if necessary, were treated for an additional 2 weeks. Sulconazole cream was significantly more effective than the vehicle in the treatment of chronic T. rubrum tinea pedis; 57% of patients were cured by sulconazole, compared with 13% cured with the vehicle. Relapse rates, assessed 2 weeks after the end of treatment, were significantly lower in patients treated with sulconazole than in those receiving vehicle (27% vs 71%). The 103 patients with moccasin-type tinea pedis whose cultures were not positive for T. rubrum achieved similar results.

Adolescent↗
PubMed1989

Properties of N-methyl-N-nitrosourea-resistant, Mex- derivatives of an SV40-immortalized human fibroblast cell line.

We have selected two N-methyl-N-nitrosourea (MNU)-resistant derivatives of the SV40-transformed, alkyltransferase-deficient (Mex-) human fibroblast cell line MRC5V1. Both derivatives remain Mex-. They are cross-resistant to methylmethanesulphonate (MMS) and 6-thioguanine (6TG) but not 2,6-diaminopurine. They show increased sensitivity to the bifunctional chloroethylating agent mitozolomide (MTZ). We have transfected MRC5V1 and one of our MNU-resistant lines with the bacterial O6-methylguanine (O6-MeG)-DNA methyltransferase (ada) gene. Transfectants of MRC5V1 are significantly more resistant to MNU but exhibit only a small increase in resistance to MMS and MTZ. Transfectants of the MNU-resistant derivative exhibit only a small additional increase in resistance to MNU, no further increase in resistance to MMS and a large increase in resistance to MTZ. The pattern of resistance to cytotoxic agents of these transfectants suggests that a second mechanism of resistance to MNU, independent of alkyltransferase expression, is operating in our resistant lines. This mechanism apparently enables the cells to tolerate O6-MeG and 6TG, but not chloroethyl adducts in their DNA.

Carcinogens↗
PubMed1989

Conserved serine-rich sequences in xylanase and cellulase from Pseudomonas fluorescens subspecies cellulosa: internal signal sequence and unusual protein processing.

The complete nucleotide sequence of the xynA gene coding for a xylanase (XYLA) expressed by Pseudomonas fluorescens subspecies cellulosa, has been determined. The structural gene consists of an open reading frame of 1833 bp followed by a TAA stop codon. Confirmation of the nucleotide sequence was obtained by comparing the predicted amino acid sequence with that derived by N-terminal analysis of purified forms of the xylanase. The signal peptide present at the N terminus of mature XYLA closely resembles signal peptides of other secreted proteins. Truncated forms of the xylanase gene, in which the sequence encoding the N-terminal signal peptide had been deleted, still expressed coli. XYLA contains domains which are homologous to an endoglucanase expressed by the same organism. These structures include serine-rich sequences. Bal31 deletions of xynA revealed the extent to which these conserved sequences, in XYLA, were essential for xylanase activity. Downstream of the TAA stop codon is a G + C-rich region of dyad symmetry (delta G = 24 kcal) characteristic of E. coli Rho-independent transcription terminators.

Amino Acid Sequence↗
PubMed1989

Hypervariable DNA fingerprinting in Escherichia coli: minisatellite probe from bacteriophage M13.

Extensive restriction-fragment-length polymorphism was revealed in Escherichia coli strains by using a region of the bacteriophage M13 genome as a DNA hybridization probe. This variation was observed across natural strains, in clinical samples, and to a lesser extent in laboratory strains. The sequence in M13 which revealed this fingerprint pattern was a region of the gene III coat protein, which contains two clusters of a 15-base-pair repeat. Oligonucleotides made to a consensus of these repeats also revealed the fingerprint profile. While this consensus sequence has significant homology to the lambda chi site sequence, an oligonucleotide made of the chi sequence did not reveal polymorphic fingerprint patterns in E. coli. The strain variation revealed by the M13 and M13-derived oligonucleotide probes will be useful for bacterial characterization and should find use in studies of bacterial evolution and population dynamics. The findings raise questions about what these repeated sequences are and why they are so variable.

Biological Evolution↗
PubMed1989

Calcium current in embryonic Xenopus muscle cells in culture.

We have investigated the appearance of calcium current in Xenopus muscle cells in 1- to 6-day-old cultures. Whole cell currents were recorded using a patch-clamp amplifier with sodium and potassium replaced with tetraethylammonium and cesium, respectively, and BaCl2 used in place of CaCl2. When the muscle membrane was depolarized above -30 mV, a slow inward current was activated, the current reached a peak amplitude near 0 mV, and an outward current became apparent above +10 mV. This slow current was enhanced by adding barium or Bay K 8644 to the extracellular recording solution and was blocked by the addition of cobalt, cadmium, or the dihydropyridines nifedipine or (+)PN 200-110. Taken together these results indicate the presence of an inward calcium current mediated through L-type channels. Thirty-one percent of the cells examined on the first day in culture showed no discernible slow inward current; however, as the age of the culture increased, all cells showed slow inward current and there was an increase in the amplitude of the current. A small proportion of the muscle cells (5 out of 34) also showed a fast activating and inactivating inward current. This current, which activated at more hyperpolarized potentials (-40 mV) was only present when 5 mM ATP was included in the internal recording solution. It also appeared to be mediated through a calcium channel but not a dihydropyridine, sensitive channel.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Effects of chronic infusion of dibutyryl c-AMP or adenosine on luteal function in sheep.

Adenosine or vehicle; dibutyryl c-AMP, a c-AMP analogue, or vehicle in two separate experiments were infused through an indwelling cannula every four hours around the ovarian vascular pedicle of ewes unilaterally ovariectomized on day 8 postestrus. Adenosine or vehicle was infused from day 8 through 22 postestrus and dibutyryl-cAMP was infused from day 8 through 20 postestrus or until the ewes returned to estrus. Interestrous intervals were greater (p less than or equal to 0.05) in ewes receiving adenosine (27.3 +/- 2.4 days) than in control ewes (17.2 +/- 1.3 days). The length of the estrous cycle of ewes receiving dibutyryl c-AMP was greater (22.4 +/- 1.1; p less than or equal to 0.05) than in control ewes which averaged 16.7 +/- 0.6 days. Profiles of progesterone were different (p less than or equal to 0.05) for ewes receiving adenosine or dibutyryl c-AMP when compared to their respective controls. In addition, the overall mean concentrations of progesterone were greater (p less than or equal to 0.05) in dibutyryl c-AMP or adenosine-treated ewes than in controls. In a third experiment, infusions of adenosine or dibutyryl c-AMP intrauterine every 4 hours through a cannula from day 8 through 22 postestrus had no effect (p less than or equal to 0.05) on the interestrous interval or profiles of progesterone. It is concluded that dibutyryl c-AMP or adenosine in vivo can delay luteolysis and adenosine and c-AMP may play roles in luteal secretion of progesterone in sheep but are probably not the uterine embryonic antiluteolysin of early pregnancy in sheep.

Adenosine↗
PubMed1989

Hydrocephalus in achondroplasia: the possible role of intracranial venous hypertension.

The significance and cause of ventriculomegaly in achondroplasia was investigated in five achondroplastic children. The intraventricular pressure (IVP) was monitored over 24 hours, followed by intraventricular injection of radionuclide alone or in combination with water-soluble contrast material. The IVP was elevated and the reabsorption of cerebrospinal fluid (CSF) into the sagittal sinus was slow in all cases, but there was no obstruction to CSF flow. The spinal subarachnoid space was well seen in all patients. Jugular venograms with pressure monitoring were obtained in four patients (bilaterally in one). These studies confirmed a narrow jugular foramen in all patients with a significant venous pressure gradient (3 to 10 mm Hg) obtained while the catheter was being pulled back from the sigmoid sinus through the foramen. A second gradient was found in the jugular vein in two patients at the level of the upper thoracic aperture. This gradient was 6 and 14 mm Hg, respectively. Identical venograms and monitoring of the venous pressure in a control group showed no pressure gradients across the jugular foramen and smaller gradients (2 to 5 mm Hg) across the thoracic inlet. It is concluded from these studies that ventriculomegaly in achondroplastic children represents hydrocephalus, which is likely secondary to raised intracranial venous pressure due to hemodynamically significant stenosis of the jugular foramen and, in some cases, the jugular vein in the thoracic aperture.

Achondroplasia↗
PubMed1989

Repair of cytotoxic lesions introduced into DNA by methylating agents.

We have investigated the biological role of O6-methylguanine and methylphosphotriesters in the DNA of mammalian cells. Our approach has been to express Escherichia coli (E. coli) DNA repair activities of well-defined specificity in Chinese hamster cells. Expression of O6-methylguanine-DNA methyltransferase is necessary and sufficient to confer resistance to the cytotoxic action of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) indicating the potential involvement of O6-methylguanine in cell killing by this compound. We present evidence that methylphosphotriesters in DNA do not constitute a cytotoxic threat. Despite this, cell lines resistant to MNNG may display elevated expression of a methylphosphotriester repair function. This may be the result of fortuitous co-amplification of transfected sequences and indicates that care should be exercised in correlating resistance to methylating agents with particular DNA repair enzymes.

Alkylating Agents↗
PubMed1988

Conserved reiterated domains in Clostridium thermocellum endoglucanases are not essential for catalytic activity.

The complete nucleotide sequence of the Clostridium thermocellum celE gene, coding for an endo-beta-1,4-glucanase (endoglucanase E; EGE) with xylan-hydrolysing activity has been determined. The structural gene consists of an open reading frame (ORF) of 2442 bp commencing with a GTG start codon and followed by a TAA stop codon. The nucleotide sequence obtained has been confirmed by comparing the predicted amino acid sequence with that derived by N-terminal amino acid sequencing of the purified protein. The EGE sequence contains a region homologous to the reiterated domain found at the C terminus of other endoglucanases from the same organism. BAL 31 deletions of the structural gene have revealed the extent to which this conserved sequence is necessary for endoglucanase and xylanase activity. A region of DNA, upstream from the structural gene has also been sequenced and a ribosome-binding site and putative promoter sequences have been identified. A second ORF which ends 349 bp 5' to the GTG start codon of the celE gene has also been identified. The encoded product contains a C terminus homologous to other C. thermocellum endoglucanases.

Amino Acid Sequence↗
PubMed1988

In vitro percutaneous absorption in mouse skin: influence of skin appendages.

Skin appendages are often envisaged as channels that bypass the stratum corneum barrier and are generally thought to facilitate the dermal absorption of topical agents. However, the significance of this transappendageal pathway in percutaneous absorption remains to be assessed experimentally. With the use of a skin organ culture penetration chamber system, the influence of skin appendages on the in vitro permeation of topically applied benzo[a]pyrene and testosterone (5 micrograms/2 cm2) was examined in skin preparations from both haired and hairless mice. Haired mice examined included the C57BL6, C3H, DBA2, Balbc, and Sencar strains and the hairless mice were the HRS and SKH. In all mouse strains examined, the overall permeation of testosterone (greater than 65% of applied dose) 16 hr following in vitro topical application was greater than that of benzo[a]pyrene (less than 10%). No strain differences were observed with respect to the percutaneous permeation of testosterone; however, percutaneous permeation of benzo[a]pyrene in the haired mice (7-10% of applied dose) was higher than that in the hairless mice (2%). In an in-house derived mouse strain which showed three phenotypic variants due to hair densities, the permeability to both compounds was highest in the skin of the haired phenotype (testosterone 67%, benzo[a]pyrene 7%), lowest in the hairless phenotype (35 and 1%, respectively) and intermediate in the fuzzy-haired animal (57 and 3%, respectively). Examination by fluorescence microscopy of cryosections of skin, prepared 1 hr after topical benzo[a]pyrene, showed areas of intense fluorescence deep within the nonfluorescing dermis of skin from the haired phenotype. These fluorescent areas were correlated with follicular ducts and sebaceous glands. In contrast, skin from the hairless phenotype showed no evidence of fluorescence in the dermis and intermediate was the fluorescence observed in the skin from the fuzzy-haired animal. These observations showed that transappendageal penetration could contribute significantly to the overall skin absorption of topical agents. They also suggest that regional distribution of skin appendages could influence the percutaneous fate of topically applied chemicals.

Animals↗
PubMed1988

Topological studies of monomeric and dimeric cytochrome c oxidase and identification of the copper A site using a fluorescence probe.

Beef heart cytochrome c oxidase was labeled at a single sulfhydryl group by treatment with 5 mM N-iodoacetylamidoethyl-1-aminonaphthalene-5-sulfonate (1,5-I-AEDANS) at pH 8.0 for 4 h. Sodium dodecyl sulfate gel electrophoresis revealed that the enzyme was exclusively labeled at subunit III, presumably at Cys-115. The high affinity phase of the electron transfer reaction with horse cytochrome c was not affected by acetylamidoethyl-1-aminonaphthalene-5-sulfonate (AEDANS) labeling. Addition of horse cytochrome c to dimeric AEDANS-cytochrome c oxidase resulted in a 55% decrease in the AEDANS fluorescence due to the formation of a 1:1 complex between the two proteins. Forster energy transfer calculations indicated that the distance from the AEDANS label on subunit III to the heme group of cytochrome c was in the range 26-40 A. In contrast to the results with the dimeric enzyme, the fluorescence of monomeric AEDANS-cytochrome c oxidase was not quenched at all by binding horse heart cytochrome c, indicating that the AEDANS label on subunit III was at least 54 A from the heme group of cytochrome c. These results support a model in which the lysines surrounding the heme crevice of cytochrome c interact with carboxylates on subunit II of one monomer of the cytochrome c oxidase dimer and the back of the molecule is close to subunit III on the other monomer. In order to identify the cysteine residues that ligand copper A, a new procedure was developed to specifically remove copper A from cytochrome c oxidase by incubation with 2-mercaptoethanol followed by gel chromatography. Treatment of the copper A-depleted cytochrome c oxidase preparation with 1,5-I-AEDANS resulted in labeling sulfhydryl groups on subunit II as well as on subunit III. No additional subunits were labeled. This result indicates that the copper A binding site is located at cysteines 196 and/or 200 of subunit II and that removal of copper A exposes these residues for labeling by 1,5-I-AEDANS. Alternative copper A depletion methods involving incubation with bathocuproine sulfonate (Weintraub, S.T., and Wharton, D.C. (1981) J. Biol. Chem. 256, 1669-1676) or p-(hydroxymercuri)benzoate (Li, P.M., Gelles, J., Chan, S.I., Sullivan, R.J., and Scott, R.A. (1987) Biochemistry 26, 2091-2095) were also investigated. Treatment of these preparations with 1,5-I-AEDANS resulted in labeling cysteine residues on subunits II and III. However, additional sulfhydryl residues on other subunits were also labeled, preventing a definitive assignment of the location of copper A using these depletion procedures.

Algorithms↗