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Biomedical subjects

G Young

Publications and source records attributed to G Young.

At least 19 recordsLinked to original sources
PubMed1999

Cloning and expression of two carbonyl reductase-like 20beta-hydroxysteroid dehydrogenase cDNAs in ovarian follicles of rainbow trout (Oncorhynchus mykiss).

In salmonid fish, 20beta-hydroxysteroid dehydrogenase (20beta-HSD) is a key enzyme involved in the production of oocyte maturation-inducing hormone (MIH), 17alpha, 20beta-dihydroxy-4-pregnen-3-one. Here we report the isolation of two cDNAs which encode proteins with high homology to carbonyl reductase-like 20beta-HSD (CR/20beta-HSD) from rainbow trout (Oncorhynchus mykiss) ovarian follicles. Genomic DNA analysis showed that the two CR/20beta-HSD cDNAs are derived from two different genes. Northern blot and RT PCR analysis demonstrated that trout CR/20beta-HSDs are broadly expressed in various tissues. Enzymatic characterization using recombinant CR/20beta-HSD proteins produced in E. coli showed that the product of one of the two cDNAs had both 20beta-HSD and CR activity, but the other had neither activity. Although the functional significance of the two genes remains unresolved, these results clearly demonstrate the presence of two distinct CR/20beta-HSD transcripts in the trout ovary.

Alcohol Oxidoreductases↗
PubMed1999

Coagulation abnormalities in the carbohydrate-deficient glycoprotein syndrome: case report and review of the literature.

The carbohydrate-deficient glycoprotein syndromes are a group of recently described autosomal recessive, metabolic defects affecting multiple systems. The disorder is caused by inefficient posttranslational glycosylation of glycoproteins. Patients with the syndrome present early in life with psychomotor retardation, seizures, hypotonia, and stroke-like episodes. They also have dysmorphic features including almond-shaped eyes, constant squint, inverted nipples, and buttock fat pads. One of the features of the syndrome is coagulopathy, and we report here a patient who presented with a prolonged activated partial thromboplastin time, and was subsequently diagnosed with the carbohydrate-deficient glycoprotein syndrome. We also summarize the results of five previously published studies of the coagulation system in these patients. Most of the reported patients are deficient in factor XI, protein C, antithrombin III, and protein S. Other coagulation proteins are less frequently affected. Both bleeding and thrombosis have been observed, yet the cause of the stroke-like episodes remains speculative. The carbohydrate-deficient glycoprotein syndrome is an increasingly recognized multisystem disorder affecting hemostasis, and thus will involve clinical hematologists as part of a multidisciplinary team caring for patients with the syndrome.

Blood Coagulation Disorders↗
PubMed1999

Sex steroid and corticosterone levels of Adélie penguins (Pygoscelis adeliae) during courtship and incubation.

Plasma levels of sex steroids (progesterone, 17alpha-hydroxyprogesterone, total androgens, and estradiol) were measured at six stages from courtship to late incubation in Adélie penguins. The pattern of change detected in the levels of plasma total androgens (males) and estradiol (females) was consistent with that found in many birds, with elevated levels during courtship (total androgens, 4 ng/ml; estradiol, 0.5 ng/ml) declining to low, stable levels during incubation. Progesterone levels declined moderately from 1.3 to 0.75-1.0 ng/ml in females following egg laying, but levels of 0.8-1.2 ng/ml persisted in males throughout the study period. 17alpha-Hydroxyprogesterone levels were consistently low (approximately 0.2 ng/ml) in females but progressively declined in males from 0.75 during courtship to <0.3 ng/ml at egg laying and during foraging. Plasma corticosterone levels were measured over the same period and were elevated in both males and females at courtship (16-18 ng/ml) and while fasting on the nest (11-15 ng/ml), but had declined in birds returning from foraging at sea, suggesting that elevated levels are related to the metabolic demands of fasting.

17-alpha-Hydroxyprogesterone↗
PubMed1999

Characteristics and occurrence of phenolic phytochemicals.

Phenolic phytochemicals are the largest category of phytochemicals and the most widely distributed in the plant kingdom. The 3 most important groups of dietary phenolics are flavonoids, phenolic acids, and polyphenols. Flavonoids are the largest group of plant phenols and the most studied. Phenolic acids form a diverse group that includes the widely distributed hydroxybenzoic and hydroxycinnamic acids. Phenolic polymers, commonly known as tannins, are compounds of high molecular weight that are divided into 2 classes: hydrolyzable and condensed tannins. Quantification of food phenolics is just beginning, and preliminary results indicate high variability, even within a given food. Phenolics are biologically active compounds that may possess some disease-preventive properties. Evidence for their ability to prevent cancer or heart disease is preliminary and conflicting. The health benefits of phytochemicals have been reported in the popular press, and the public will come to dietitians for answers to their questions about phytochemicals.

Coumaric Acids↗
PubMed1999

Omafilcon A (Proclear) soft contact lenses in a dry eye population.

PURPOSE: We conducted a 3-month, randomized, comparative cross-over study to evaluate the clinical performance of lenses manufactured from omafilcon A on subjects with signs and symptoms of dry eye. The subjects' own daily wear soft lenses were used as controls. METHODS: Seventy-six subjects with objective evidence of dry eye, as defined in the NEI/Industry Workshop Report 1995, were fit with either the omafilcon A lenses (Proclear) or new control lenses. Subjects wore the lenses for 6 weeks and then crossed over to bilateral wear of the other lenses for an additional 6 weeks. During each part of the study, we examined subjects at 1 week, 1 month, and 6 weeks. Signs and symptoms of dry eye were evaluated, and on-eye dehydration of the lens was assessed. RESULTS: When the subjects were wearing the omafilcon A lenses, there was a statistically significant improvement in a number of subjective parameters including comfort, dryness, frequency of eye irritation, and frequency of burning. We found significantly less on-eye dehydration of the lens and fluorescein corneal staining with the omafilcon A lenses. CONCLUSIONS: This study indicated that the daily wear of omafilcon A lenses provided better comfort, fewer symptoms, less on-eye dehydration, and less fluorescein corneal staining than other soft daily wear contact lenses in subjects with mild to moderate dry eye.

Adolescent↗
PubMed1998

Eel (Anguilla japonica) testis 11beta-hydroxylase gene is expressed in interrenal tissue and its product lacks aldosterone synthesizing activity.

A recombinant expression vector containing Japanese eel (Anguilla japonica) testis cytochrome P450(11 beta) (11beta-hydroxylase) cDNA was introduced into COS-1 cells. Enzymatic activity of the expressed P450(11 beta) for corticosteroid synthesis was analysed by incubating transfected cells with 14C-labelled 11-deoxycorticosterone or 3H-labelled deoxycortisol as substrates. Thin layer chromatography of incubation medium revealed that a high percentage of 11-deoxycorticosterone was converted into corticosterone and 11-dehydrocorticosterone but no aldosterone was detected. Similarly, deoxycortisol was converted into cortisol and cortisone. These results show that eel P450(11beta) does not possess significant aldosterone synthesizing activity. Northern blot analysis detected a 1.8 kb transcript of P450(11beta) using RNA extracted from interrenals of untreated Japanese eel but no hybridization signal was apparent using RNA extracted from brain, spleen, heart, muscle or testis. Immunohistochemistry using an antiserum against P450(11beta) also revealed strong immunostaining in interrenal cells.

Aldosterone↗
PubMed1998

Positive-outcome bias and other limitations in the outcome of research abstracts submitted to a scientific meeting.

CONTEXT: Studies with positive results are more likely to be published in biomedical journals than are studies with negative results. However, many studies submitted for consideration at scientific meetings are never published in full; bias in this setting is poorly studied. OBJECTIVE: To identify features associated with the fate of research abstracts submitted to a scientific meeting. DESIGN AND SETTING: Prospective observational cohort, with 5-year follow-up of all research submitted for consideration to the major annual 1991 US research meeting in the specialty of emergency medicine. PARTICIPANTS: All research abstracts submitted for consideration at the meeting for possible presentation. MAIN OUTCOME MEASURES: Characteristics associated with acceptance for presentation at the meeting and subsequent publication as a full manuscript. RESULTS: A total of 492 research abstracts were submitted from programs in emergency medicine and other specialties affiliated with 103 US medical schools. A total of 179 (36%) were accepted for presentation and 214 (43%) were published in 44 journals. Of the 179 abstracts accepted for presentation, 111 studies were published. Scientific quality of abstracts or prestige of the journal in which the study was eventually published did not predict either of these outcomes. The best predictors (by logistic regression) of meeting acceptance were a subjective "originality" factor (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.13-3.89) and positive results (OR, 1.99; 95% CI, 1.07-3.84), and, for publication, meeting acceptance (OR, 2.49; 95% CI, 1.49-4.35) and large sample size (OR, 2.26; 95% CI, 1.23-4.31). Forty-nine percent (241) of abstracts did not report on blinding, and 24% (118) did not report on randomization. Acceptance and publication were both more likely for positive outcomes (P=.03). Funnel plots showed the classic distribution of positive-outcome ("publication") bias at each of the submission, acceptance, and publication phases. Meeting acceptance predicted publication with a sensitivity of only 51%, specificity of 71%, positive predictive value of 57%, and negative predictive value of 66%. CONCLUSIONS: Positive-outcome bias was evident when studies were submitted for consideration and was amplified in the selection of abstracts for both presentation and publication, neither of which was strongly related to study design or quality.

Abstracting and Indexing↗
PubMed1998

Unpublished research from a medical specialty meeting: why investigators fail to publish.

CONTEXT: It is not known whether peer review of research abstracts submitted to scientific meetings influences subsequent attempts at publication. OBJECTIVE: To determine why research submitted to a scientific meeting is not subsequently published. We hypothesized that authors of abstracts rejected by a meeting are less likely to pursue publication than those whose abstracts are accepted, regardless of research quality. DESIGN AND PARTICIPANTS: Blinded review of abstracts submitted to a medical specialty meeting in 1991 and not published as full manuscripts within 5 years. In 1996, authors of 266 unpublished studies were asked to complete questionnaires. MAIN OUTCOME MEASURES: Submission of a full manuscript to a journal between 1991 and 1996; failure to submit a manuscript to a journal because the investigator believed it would not be accepted for publication. RESULTS: A total of 223 (84%) of the unpublished investigators returned the questionnaire. Only 44 (20%) had submitted manuscripts to a journal. Manuscript submission was not associated with abstract quality (odds ratio [OR], 1.16; 95% confidence interval [CI], 0.80-1.64), positive results (OR, 0.75; 95% CI, 0.31-1.57), or other study characteristics. Having an abstract accepted for presentation at the meeting weakly predicted submission of a manuscript to a journal (OR, 1.88; 95% CI, 0.84-4.10). Authors of accepted abstracts were significantly less likely to believe a journal would not publish their manuscript than were authors of rejected abstracts (OR, 0.23; 95% CI, 0.0001-0.61). CONCLUSIONS: Study characteristics do not predict attempts to publish research submitted to a scientific meeting. Investigators whose research is rejected by a meeting are pessimistic about chances for publication and may make less effort to publish.

Abstracting and Indexing↗
PubMed1998

Use of pamidronate in the management of acute cancer-related hypercalcemia in children.

PURPOSE: To determine whether pamidronate is a safe and effective agent for the treatment of severe hypercalcemia of malignancy in children. MATERIALS AND METHODS: A retrospective review of the charts of five children treated with pamidronate 1-2 mg/kg for severe, refractory hypercalcemia of malignancy. All children failed conventional therapy. Statistical analysis was done utilizing the two-tailed Student's t-test. RESULTS: All five children had complete resolution of their hypercalcemia in a predictable pattern within 24-48 hours. The average decrease in serum calcium was 1.63 mmol/L (6.54 mg/dl). (P < .01) The adverse effects were mild and transient, and consisted of hypocalcemia, hypophosphatemia, and hypomagnesemia. CONCLUSIONS: Pamidronate at a dose of 1 mg/kg is a safe and effective treatment for severe, refractory hypercalcemia of malignancy in children.

Acute Disease↗
PubMed1998

Immunolocalization of steroidogenic enzymes (P450scc, P450c17, P450arom, and 3beta-HSD) in immature and mature testes of rainbow trout (Oncorhynchus mykiss).

We examined the localization of steroidogenic cells in rainbow trout (Oncorhynchus mykiss) testis during spermatogenesis by using polyclonal antibodies generated against rainbow trout cholesterol side-chain cleavage enzyme cytochrome P450 (P450scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 17alpha-hydroxylase/C17,21 lyase (P450c17), and aromatase cytochrome P450 (P450arom) as markers of steroid production. Since we had previously produced specific antibodies against 3beta-HSD and P450arom, antibodies against oligopeptides corresponding to C-terminal sequences of P450scc and P450c17, predicted from rainbow trout P450scc and P450c17 cDNAs, were produced in this study. These two antibodies recognized 54-kDa (P450scc) and 59-kDa (P450c17) bands specifically in several steroidogenic organs, i.e., testis, ovary, and interrenal tissue (head kidney) in Western blots. Immunohistochemically, immunoreactive P450scc, P450c17, and 3beta-HSD, but not P450arom, were found only in interstitial Leydig cells of immature and mature testes. Immunoreactive P450arom was not detected in either testis. This study suggests that Sertoli cells and germ cells of rainbow trout testis do not contain P450scc, P450c17, P450arom, or 3beta-HSD.

3-Hydroxysteroid Dehydrogenases↗
PubMed1998

Thrombopoietin levels in HIV-associated thrombocytopenia in children.

OBJECTIVES: To determine the mechanism of human immunodeficiency virus (HIV)-associated thrombocytopenia by using thrombopoietin (TPO) levels. STUDY DESIGN: TPO levels were measured in 14 HIV+ children with thrombocytopenia (TCP+), 28 HIV+ children without thrombocytopenia (TCP-), and 15 matched control subjects. RESULTS: For the patients with moderate symptoms, TPO levels were similar for the TCP+ and TCP- groups (251 pg/mL vs 263 pg/mL; P =.98) and similar to those of control subjects. For the patients with severe symptoms, TPO levels were significantly higher for the TCP+ group versus the TCP- group (1172 pg/mL vs 222 pg/mL; P =.03). Patients with severe symptoms and thrombocytopenia had significantly higher TPO levels than those with moderate symptoms and thrombocytopenia (P <.005), were more likely to require growth factors, and did not respond to treatment with intravenous immunoglobulin. CONCLUSIONS: TPO levels can distinguish 2 groups of patients with HIV-associated thrombocytopenia. Patients with severe disease had elevated TPO levels, did not respond to treatment with intravenous immunoglobulin, and were more likely to be growth factor-dependent, suggesting marrow failure.

Child↗
PubMed1998

Radiological assessment in psoriatic arthritis.

Our objective was to compare the reliability and responsiveness of the original Steinbrocker's (OS), our modified Steinbrocker's (MS) and Larsen's (L) radiological scoring methods for detecting radiological change in psoriatic arthritis over time. Two sets of radiographs of the hands and feet at least 2 yr apart were selected from 68 patients. Films were randomly presented and scored independently by a rheumatologist (DDG) and a radiologist (DS), in a blinded fashion using all methods. The index of reliability was the intraclass coefficient (ICC) and the responsiveness was assessed using plots and regression analyses. All three radiological scoring methods have excellent interobserver and good intra-observer reliability. L and MS are equally responsive and superior to OS in detecting change in joint damage over time. Thus, the L or MS radiological scoring methods can be used to monitor disease progression in psoriatic arthritis.

Adult↗
PubMed1998

The impact of molecular diagnosis on familial colorectal cancer.

We have shown the impact of molecular diagnostics related to mutation detection in an extensive family with a strong history of colorectal cancer. The nature and presentation of the cancers suggested that hereditary nonpolyposis colorectal cancer was the most likely cause. The strategies employed have enabled the detection and characterisation of the causative mutation in the proband and predictive testing in the remaining relatives where requested. Using the chemical cleavage of mismatches technique and direct sequencing, the MSH2 and MLH1 genes of the proband were investigated. A single base substitution, C-->T at nucleotide 350, codon 117, of the MLH1 gene was identified. Across the family pedigree at specific points, 22 other relatives have been tested for the mutation by direct DNA sequencing from genomic DNA. Of the total of 23 patients tested to date, 11 have the mutation. In conjunction with appropriate genetic counselling, this service has clarified the genetic status of many individuals within this family. Predictive information provided prior to the development of symptoms enables individuals to make informed choices regarding disease management and the future, removing the anxiety associated with the unknown.

Adaptor Proteins, Signal Transducing↗
PubMed1998

The use of sulfasalazine in psoriatic arthritis: a clinic experience.

OBJECTIVE: To assess the tolerability of sulfasalazine in a clinic setting and determine its longterm effectiveness with respect to articular disease and prevention of radiographic progression in patients with psoriatic arthritis (PsA). METHODS: Patients who were given sulfasalazine during their attendance at the University of Toronto Psoriatic Arthritis Clinic were enrolled in the study. For patients that were able to tolerate sulfasalazine for at least 3 months a matched control was identified who did not receive sulfasalazine. The primary outcome measures were the tolerability of sulfasalazine, clinical response of the actively inflamed joints at 6 and 12 months, and the change in radiographic score at 24 months. RESULTS: Thirty-six patients received sulfasalazine. Fourteen of 16 patients discontinued sulfasalazine due to one or more side effects occurring within 3 months of treatment initiation. For the remaining 20 patients, a 50% reduction in actively inflamed joint count was noted in 7/20 patients at 6 months and 11/15 patients at 12 months, compared to 7/19 patients in the control group at 6 months and 10/20 patients at 12 months. The mean change in the radiographic score at 24 months between the 2 groups was not statistically significant. CONCLUSION: Sulfasalazine was not well tolerated in patients with PsA in our clinic. For those able to tolerate sulfasalazine, there was no evidence of a treatment effect with respect to articular involvement. In addition, sulfasalazine does not appear to halt radiographic progression in PsA.

Adolescent↗
PubMed1997

Pharmacokinetics and safety of tobramycin after once-daily administration in patients with cystic fibrosis.

STUDY OBJECTIVE: Tobramycin is commonly used to treat respiratory tract infections in patients with cystic fibrosis. We designed a study to determine the pharmacokinetics and safety of once-daily dosing of tobramycin in this population. DESIGN: Multiple blood samples were collected from each patient, and serum concentrations of tobramycin were determined by a fluorescence polarization immunoassay. Blood urea nitrogen and serum creatinine levels were measured every 2 to 3 days, and audiometric evaluations were performed at the start and end of therapy. MEASUREMENTS AND RESULTS: Eighteen patients (mean age, 24.6 years) received tobramycin at doses of 7 to 15 mg/kg/d as a single-dose infusion over 20 min. The maximum serum concentration of tobramycin ranged from 40.1 to 64.6 mg/L. A mean dose of 11.9+/-1.9 mg/kg was needed to obtain a theoretical mean peak serum concentration of 42.4+/-4.5 mg/L. The mean total body clearance, apparent volume of distribution, and elimination half-life was 1.7+/-0.4 mL/min/kg, 0.27+/-0.06 L/kg, and 1.8+/-0.3 h, respectively. The period of time that the serum concentration exceeded eight times the theoretical minimum inhibitory concentration of 1 mg/L ranged from 2.1 to 4.4 h, which was nearly five times longer compared with the use of divided daily doses in the same patients during previous hospitalizations. No nephrotoxicity, ototoxicity, or adverse effects occurred in any patient. CONCLUSION: Based on our data, tobramycin may be used safely in once-daily doses to treat exacerbations of respiratory tract infections in patients with cystic fibrosis.

Adolescent↗
PubMed1997

Canine chondrocytes seeded in type I and type II collagen implants investigated in vitro.

Synthetic and natural absorbable polymers have been used as vehicles for implantation of cells into cartilage defects to promote regeneration of the articular joint surface. Implants should provide a pore structure that allows cell adhesion and growth, and not provoke inflammation or toxicity when implanted in vivo. The scaffold should be absorbable and the degradation should match the rate of tissue regeneration. To facilitate cartilage repair the chemical structure and pore architecture of the matrix should allow the seeded cells to maintain the chondrocytic phenotype, characterized by synthesis of cartilage-specific proteins. We investigated the behavior of canine chondrocytes in two spongelike matrices in vitro: a collagen-glycosaminoglycan (GAG) copolymer produced from bovine hide consisting of type I collagen and a porous scaffold made of type II collagen by extraction of porcine cartilage. Canine chondrocytes were seeded on both types of matrices and cultured for 3 h, 7 days, and 14 days. The histology of chondrocyte-seeded implants showed a significantly higher percentage of cells with spherical morphology, consistent with chondrocytic morphology, in the type II sponge at each time point. Pericellular matrix stained for proteoglycans and for type II collagen after 14 days. Biochemical analysis of the cell seeded sponges for GAG and DNA content showed increases with time. At day 14 there was a significantly higher amount of DNA and GAG in the type II matrix. This is the first study that directly compares the behavior of chondrocytes in type I and type II collagen matrices. The type II matrix may be of value as a vehicle for chondrocyte implantation on the basis of the higher percentage of chondrocytes retaining spherical morphology and greater biosynthetic activity that was reflected in the greater increase of GAG content.

Animals↗