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Biomedical subjects

J Taylor

Publications and source records attributed to J Taylor.

At least 235 records · Page 13Linked to original sources
PubMed1998

Antisocial behavior, substance use, and somatization in families of adolescent drug abusers and adolescent controls.

Symptoms of conduct disorder (CD), antisocial personality disorder (ASP), alcohol abuse, drug abuse, and somatization were tabulated for the families of 35 delinquent, substance-abusing (multiple-problem) adolescent male probands and 35 age-matched control males. Alcohol abuse, CD/ASP, and somatization were assessed with either the Diagnostic Interview Schedule (DIS) (for participants aged 18 and up) or the Diagnostic Interview for Children and Adolescents (DICA) (for participants aged 12 to 17). Drug abuse for all participants was assessed with the Substance Abuse Module (SAM) of the Comprehensive Interview for Diagnostic Evaluation (CIDE). As expected, proband groups had significantly more (p < .0001) CD/ASP, alcohol abuse, and drug abuse symptoms than control groups. A significant (p < .01) positive correlation among CD/ASP, alcohol abuse, and drug abuse was found for each group. Somatization was not differentially associated with proband status. It was concluded that identifying male multiple-problem youths also identifies families with a high incidence of similar problems.

Adolescent↗
PubMed1998

The efficacy and safety of dorzolamide as adjunctive therapy to timolol maleate gellan solution in patients with elevated intraocular pressure. Additivity Study Group.

PURPOSE: Two parallel, randomized, double-masked, placebo-controlled studies were conducted to assess the efficacy and safety of 2% dorzolamide hydrochloride as adjunctive therapy to 0.5% timolol maleate ophthalmic gellan (gel-forming) solution in patients with elevated intraocular pressure (IOP) that was inadequately controlled with 0.5% timolol maleate gellan solution alone. METHODS: Both studies began with an open-label 2-week run-in period on 0.5% timolol maleate gellan solution once a day. The only variation in method between the two studies was the dosage of 2% dorzolamide. In one study, 202 patients received 0.5% timolol maleate gellan solution once daily plus either 2% dorzolamide or placebo three times daily. In the other study, 181 patients received 0.5% timolol maleate gellan solution once daily plus either 2% dorzolamide or placebo twice daily. RESULTS: After 85 days, additional mean percent reductions in IOP from baseline at morning trough for the groups receiving 2% dorzolamide three times daily and placebo three times daily were 12.5% and 8.4%, respectively. Mean percent reductions for the groups receiving 2% dorzolamide twice daily and placebo twice daily were 13.1% and 6.5%, respectively. Burning and/or stinging on instillation were the only adverse experiences that affected significantly more of the patients receiving 2% dorzolamide twice or three times daily than those receiving placebo. CONCLUSION: When administered concomitantly with 0.5% timolol maleate gellan solution, 2% dorzolamide three times daily or twice daily produced a statistically significant reduction in IOP at morning trough and peak and was generally well tolerated.

Adrenergic beta-Antagonists↗
PubMed1997

Human estrogen receptor beta binds DNA in a manner similar to and dimerizes with estrogen receptor alpha.

The cloning of a novel estrogen receptor beta (denoted ERbeta) has recently been described (Kuiper, G. G. J. M., Enmark, E., Pelto-Huikko, M., Nilsson, S., and Gustafsson, J-A. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 5925-5930 and Mosselman, S., Polman, J. , and Dijkema, R. (1996) FEBS Lett. 392, 49-53). ERbeta is highly homologous to the "classical" estrogen receptor alpha (here referred to as ERalpha), has been shown to bind estrogens with an affinity similar to that of ERalpha, and activates expression of reporter genes containing estrogen response elements in an estrogen-dependent manner. Here we describe functional studies comparing the DNA binding abilities of human ERalpha and beta in gel shift assays. We show that DNA binding by ERalpha and beta are similarly affected by elevated temperature in the absence of ligand or in the presence of 17beta-estradiol and the partial estrogen agonist 4-hydroxy-tamoxifen. In the absence of ligand, DNA binding by ERalpha and beta is rapidly lost at 37 degrees C, while in the presence of 17beta-estradiol and 4-hydroxy-tamoxifen, the loss in DNA binding at elevated temperature is much more gradual. We show that the loss in DNA binding is not due to degradation of the receptor proteins. However, while the complete antagonist ICI 182, 780 does not "protect" human ERalpha (hERalpha) from loss of DNA binding at elevated temperature in vitro, it does appear to protect human ERbeta (hERbeta), suggestive of differences in the way ICI 182, 780 acts on hERalpha and beta. We further report that ERalpha and beta can dimerize with each other, the DNA binding domain of hERalpha being sufficient for dimerization with hERbeta. Cell and promoter-specific transcription activation by ERalpha has been shown to be dependent on the differential action of the N- and C-terminal transcription activation functions AF-1 and AF-2, respectively. The existence of a second estrogen receptor gene and the dimerization of ERalpha and beta add greater levels of complexity to transcription activation in response to estrogens.

Animals↗
PubMed1997

MutS mediates heteroduplex loop formation by a translocation mechanism.

Interaction of Escherichia coli MutS and MutL with heteroduplex DNA has been visualized by electron microscopy. In a reaction dependent on ATP hydrolysis, complexes between a MutS dimer and a DNA heteroduplex are converted to protein-stabilized, alpha-shaped loop structures with the mismatch in most cases located within the DNA loop. Loop formation depends on ATP hydrolysis and loop size increases linearly with time at a rate of 370 base pairs/min in phosphate buffer and about 10,000 base pairs/min in the HEPES buffer used for repair assay. These observations suggest a translocation mechanism in which a MutS dimer bound to a mismatch subsequently leaves this site by ATP-dependent tracking or unidimensional movement that is in most cases bidirectional from the mispair. In view of the bidirectional capability of the methyl-directed pathway, this reaction may play a role in determination of heteroduplex orientation. The rate of MutS-mediated DNA loop growth is enhanced by MutL, and when both proteins are present, both are found at the base of alpha-loop structures, and both can remain associated with excision intermediates produced in later stages of the reaction.

Adenosine Triphosphatases↗
PubMed1997

Stromal estrogen receptors mediate mitogenic effects of estradiol on uterine epithelium.

Estradiol-17beta (E2) acts through the estrogen receptor (ER) to regulate uterine growth and functional differentiation. To determine whether E2 elicits epithelial mitogenesis through epithelial ER versus indirectly via ER-positive stromal cells, uteri from adult ER-deficient ER knockout (ko) mice and neonatal ER-positive wild-type (wt) BALB/c mice were used to produce the following tissue recombinants containing ER in epithelium (E) and/or stroma (S), or lacking ER altogether: wt-S + wt-E, wt-S + ko-E, ko-S + ko-E, and ko-S + wt-E. Tissue recombinants were grown for 4 weeks as subrenal capsule grafts in intact female nude mice, then the hosts were treated with either E2 or oil a week after ovariectomy. Epithelial labeling index and ER expression were determined by [3H]thymidine autoradiography and immunohistochemistry, respectively. In tissue recombinants containing wt-S (wt-S + wt-E, wt-S + ko-E), E2 induced a similar large increase in epithelial labeling index compared with oil-treated controls in both types of tissue recombinants despite the absence of epithelial ER in wt-S + ko-E tissue recombinants. This proliferative effect was blocked by an ER antagonist, indicating it was mediated through ER. In contrast, in tissue recombinants prepared with ko-S (ko-S + ko-E and ko-S + wt-E), epithelial labeling index was low and not stimulated by E2 despite epithelial ER expression in ko-S + wt-E grafts. In conclusion, these data demonstrate that epithelial ER is neither necessary nor sufficient for E2-induced uterine epithelial proliferation. Instead, E2 induction of epithelial proliferation appears to be a paracrine event mediated by ER-positive stroma. These data in the uterus and similar studies in the prostate suggest that epithelial mitogenesis in both estrogen and androgen target organs are stromally mediated events.

Aging↗
PubMed1997

Bilateral reduction mammoplasty in a patient treated with calcium channel blocker and cyclosporine after renal transplant: a case report.

A 28-year-old woman with end-stage renal disease secondary to diabetes mellitus and hypertension underwent cadaver renal transplant in April 1992. After surgery, she developed bilateral breast enlargement while she was taking cyclosporine for immunosuppression therapy and felodipine, a calcium channel blocker, for blood pressure control. She underwent bilateral reduction mammoplasty in June 1995 to treat progressive breast enlargement which interfered with her normal life activities. Through mechanisms only partially understood, calcium channel blockers and cyclosporine are reported to increase the serum prolactin level, producing gynecomastia in men. There is no report in current literature to support a similar phenomenon in women.

Adult↗
PubMed1997

Streptococcus pyogenes type 5 M protein is an antigen, not a superantigen, for human T cells.

M proteins are coiled-coil dimers expressed on group A streptococcal cell surfaces. They have an important role in host antistreptococcal immunity and in poststreptococcal autoimmune sequelae. Controversy has arisen regarding whether type 5 M proteins are superantigenic for human T cells. To investigate this, we have produced and tested M5 in the form of two novel recombinant proteins. We found no evidence of superantigenicity using either recombinant whole M5 protein (rM5) or recombinant pep M5 protein (rpepM5) to activate peripheral blood mononuclear cells (PBMC) from healthy adult volunteers. Short-term, rM5-specific T-cell lines from different subjects were uniformly self-APC restricted and showed no consistent pattern of TCR V beta usage. A synthetic peptide of M5 residues 217-237 was found to contain epitope(s) recognized by some rM5-specific human T cells. PBMC responses to rM5 and rpepM5 in 3- and 7-day proliferation assays were characteristic of antigenic rather than superantigenic stimulation. We conclude that type 5 M protein activates human T cells as a conventional antigen.

Adult↗
PubMed1997

The contemporary demography of indigenous Australians.

"Increased public policy focus on indigenous Australians over the past 30 years has resulted in a substantial expansion of demographic analysis over the same period. This paper reviews these efforts and summarizes the main topics, findings and debates. The accumulated evidence points to both demographic change and continuity. Change: in that mortality has declined; fertility levels have been much reduced; urbanization has burgeoned and population growth has entered a phase of rapid increase. Continuity: because mortality is still much higher than the Australian average; fertility remains at a level well above that reported for all women; most individuals still live away from major cities; and the estimation of overall numbers still hinges on a social construction of identity."

Australia↗
PubMed1997

Magnetic resonance renography: optimisation of pulse sequence parameters and Gd-DTPA dose, and comparison with radionuclide renography.

The aim of this study was to assess the feasibility of magnetic resonance renography (MRR) using gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) in comparison with conventional radionuclide renography (RR) using technetium-99m-DTPA (99mTc-DTPA). MRR has many advantages over RR, including lack of ionising radiation, increased spatial resolution, and visible background anatomy. By optimising the pulse sequence, we developed an MRR protocol in which signal intensity is linear with Gd-DTPA concentration over a clinically relevant range. Twenty-nine patients and a volunteer were studied using this protocol. Magnetic resonance renography was performed using three different doses of Gd-DTPA: 0.1 mmol kg-1 (n = 13), 0.05 mmol kg-1 (n = 7), and 0.025 mmol kg-1 (n = 9). Each patient was also assessed using radionuclide renography. The resulting renograms were assessed in terms of time to peak signal intensity, signal decrease after peak, and kidney function ratios calculated from both the areas underneath and the slopes of the uptake curves. We have shown that the MR renograms obtained using low dose Gd-DTPA correlate best with the radionuclide renograms. Remaining discrepancies may be explained by variations in the injection procedures (hence in arterial input functions) and the limited coverage of the three MRR slices compared to the whole body projection of RR. Furthermore, at high local concentrations, signal becomes independent of T1 and is dominated by T2.

Adult↗
PubMed1997

Correlative MR imaging and 31P-MR spectroscopy study in sarcoglycan deficient limb girdle muscular dystrophy.

We combined magnetic resonance (MR) imaging and phosphorus magnetic resonance spectroscopy (31P-MRS) to study skeletal muscle in seven patients with limb girdle muscular dystrophy (LGMD) with a variable deficiency of the alpha-, beta-, and gamma-sarcoglycan but normal dystrophin expression on muscle biopsy. T1- and T2-weighted spin-echo axial leg images showed the highest degree of fat replacement in soleus, tibialis anterior and peroneal muscles while gastrocnemius and tibialis posterior were less affected. In LGMD patients as a group, calf muscle phosphorylated compound content did not differ from controls, but the cytosolic pH was increased (P = 0.02). The degree of calf muscle fat replacement correlated inversely with cytosolic pH (r = 0.74) and directly with PCr/ATP (r = 0.74). Muscle oxidative metabolism was normal in LGMD patients. Our findings show that primary deficits of sarcoglycan complex lead to specific morphological and metabolic patterns of skeletal muscle involvement.

Adolescent↗
PubMed1997

Early onset autosomal dominant myopathy with rigidity of the spine: a possible role for laminin beta 1?

We describe 17 individuals from seven families with a slowly progressive, early onset, autosomal dominant myopathy with proximal muscle weakness, calf hypertrophy, contractures, spinal rigidity and, in five of the adult cases, a cardiac conduction defect. A deficiency of the laminin beta 1 chain of the skeletal muscle fibres was found in the older individuals of these families, but not the younger members. Other laminin chains, dystrophin and the dystrophin-associated glycoproteins were normal. The age-related deficiency of the laminin beta 1 is restricted to the skeletal muscle fibres and not the vascular tissue, suggesting that this may be a secondary phenomenon. These findings suggest that a laminin or a laminin-binding protein is implicated in some forms of dominant limb girdle myopathies.

Adolescent↗
PubMed1997

Data compression of fetal Doppler ultrasound audio signals using zero-crossings analysis.

This paper outlines a method of reducing the data rate for transmitting fetal Doppler ultrasound audio signals. A specific application is cited where compression of the fetal Doppler signal is required to transmit information to cardiotocographs (CTGs) using radio telemetry. The method involves splitting the signal into amplitude and frequency components. The amplitude is represented by samples of the signal envelope whilst the frequency information is represented by the number of zero-crossings within fixed intervals (windows). With a careful choice of window size, it is shown that this method can be used to reproduce the signal with no audible difference when compared with the original waveform. A reduction in data rate of 15:1 is achieved.

Algorithms↗
PubMed1997

T-cell antigen receptor transmembrane peptides modulate T-cell function and T cell-mediated disease.

This study describes a novel method of inhibiting T-cell function by the use of peptides rationally designed from the T-cell antigen receptor (TCR) alpha-chain transmembrane sequence involved with TCR receptor assembly. The most effective peptide (core peptide, CP) modulating in vitro and in vivo T-cell function contained nine amino acids two of which, lysine and arginine, were hydrophilic and separated by four hydrophobic amino acids. CP without chemical modification or conjugation was able to enter non-T and T cells. Conjugation of CP at the carboxyl terminus with palmitic acid resulted in a greater inhibition of T-cell interleukin-2 (IL-2) production in vitro than peptide alone. When examined for effects in vivo, CP reduced clinical signs of inflammation in three T cell-mediated disease models including adjuvant-induced arthritis, experimental allergic neuritis, and cyclophosphamide-induced diabetes in NOD/Lt(F) mice. This peptide or its analogues has potential as a therapeutic agent in human inflammatory and autoimmune disorders.

Amino Acid Sequence↗
PubMed1997

Apoptosis in cerebellar granule neurones: involvement of interleukin-1 beta converting enzyme-like proteases.

Proteases of the interleukin-1 beta converting enzyme (ICE) family have been implicated as mediators of apoptosis in several cell types. Here we report the ability of peptide inhibitors of ICE-like proteases to inhibit apoptosis of cultured cerebellar granule neurones caused by reduction of extracellular K+ levels and by the broad-spectrum protein kinase inhibitor staurosporine. Unlike apoptosis induced by K+ deprivation, staurosporine-induced neuronal death does not require new protein synthesis. The ICE-like protease inhibitor benzyloxycarbonyl-Val-Ala-Asp (O-methyl)fluoromethyl ketone (zVAD-fmk) was found to be extremely effective at preventing staurosporine-induced death of cerebellar granule neurones and yet was completely ineffective in preventing K+ deprivation-induced death. Staurosporine induced cleavage of the 116-kDa poly (ADP-ribose) polymerase enzyme, a substrate of ICE-like proteases, to the 85-kDa product, and this cleavage was also blocked by zVAD. By comparison, K+ deprivation led to the disappearance of the 116-kDa protein, with no detectable increase in level of the 85-kDa cleavage product. Taken together, these results imply the existence of divergent ICE-like protease pathways in a CNS model of neuronal apoptosis.

Amino Acid Chloromethyl Ketones↗
PubMed1997

Evaluation of the toxicity of ISIS 2302, a phosphorothioate oligonucleotide, in a 4-week study in CD-1 mice.

The subchronic toxicity of ISIS 2302 and ISIS 3082, phosphorothioate oligonucleotides with antisense activity against human and murine ICAM-1 mRNA, respectively, was investigated in CD-1 mice. ISIS 2302 is currently in clinical trials as an anti-inflammatory agent. Because of the differences in mRNA sequence targets between humans and mice, ISIS 2302 has no pharmacologic activity in mice. ISIS 3082 was specifically designed to inhibit murine ICAM-1 and was included in this study to evaluate the effects of prolonged ICAM-1 inhibition. The oligonucleotides were administered by bolus i.v. injection (via tail vein) every other day for 27 days (14 doses) at dose levels of 0, 0.8, 4, 20, and 100 mg/kg per injection ISIS 2302 or 20 mg/kg per injection ISIS 3082. The basic group size consisted of 10 male and 10 female mice, which were sacrificed 2 days after the last dose and an additional 5 mice per sex in vehicle control and 100 mg/kg ISIS 2302 dose groups, which remained on study for a 28-day treatment-free period. No treatment-related deaths occurred during this study, and there were no effects of either oligonucleotide on body weight gain or food consumption. The most common changes observed in this study included a mixed mononuclear cell infiltrate seen in a number of organs or tissues, splenomegaly, and lymphoid hyperplasia at dose levels of > or = 20 mg/kg ISIS 2302. In the group that received the highest dose level of ISIS 2302 (100 mg/kg), there were alterations in serum chemistry parameters that appeared to be related to perturbations in the liver, including 3- to 4-fold increases in aspartate and alanine aminotransferase and smaller changes in bilirubin, alkaline phosphatase, cholesterol, triglycerides, and albumin levels. Treatment-related effects on hematologic parameters were limited to the 100 mg/kg ISIS 2302 dose group and included slight monocytosis and thrombocytopenia. None of the effects observed appeared to be life threatening. Complete or partial reversal of all effects was evident in the remaining high-dose ISIS 2302 animals at the end of the 4-week recovery period. Comparison of the effects produced by the same dose level (20 mg/kg) of ISIS 2302 and ISIS 3082 did not reveal any differences that could be attributed to exaggerated pharmacology. In conclusion, treatment-related alterations were observed primarily at the 100 mg/kg dose level, including immune stimulation and hepatic alterations, which were partially reversed following a 4-week treatment-free period.

Animals↗
PubMed1997

Avoided and avoidable risks of cancer.

Despite the considerable efforts and funds devoted to cancer research over several decades, cancer still remains a mainly lethal disease. Cancer incidence and mortality have not declined at the same rate as other major causes of death, indicating that primary prevention remains a most valuable approach to decrease mortality. There is general agreement that environmental exposures are variously involved in the causation of the majority of cancer cases and that at least half of all cancers could be avoided by applying existing etiologic knowledge. There is disagreement, however, regarding the proportion of cancer risks attributable to specific etiological factors, including diet, occupation and pollution. Estimates of attributable risks are largely based today on unverified assumptions and the calculation of attributable risks involves taking very unequal evidence of various types of factors and treating them equally. Effective primary prevention resulting in a reduction of cancer risk can be obtained by: (i) a reduction in the number of carcinogens to which humans are exposed; or (ii) a reduction of the exposure levels to carcinogens. Exposure levels that could be seen as sufficiently low when based on single agents, may actually not be safe in the context of the many other concomitant carcinogenic and mutagenic exposures. The list of human carcinogens and of their target organs might be quite different if: (i) epidemiological data were available for a larger proportion of human exposures for which there is experimental evidence of carcinogenicity; (ii) more attention was paid to epidemiological evidence that is suggestive of an exposure-cancer association, but is less than sufficient, particularly in identifying target organs; and (iii) experimental evidence of carcinogenicity, supported by mechanistic considerations, were more fully accepted as predictions of human risk.

Carcinogenicity Tests↗