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Biomedical subjects

J Collins

Publications and source records attributed to J Collins.

At least 181 records · Page 10Linked to original sources
PubMed1996

CP-154,526: a potent and selective nonpeptide antagonist of corticotropin releasing factor receptors.

Here we describe the properties of CP-154,526, a potent and selective nonpeptide antagonist of corticotropin (ACTH) releasing factor (CRF) receptors. CP-154,526 binds with high affinity to CRF receptors (Ki < 10 nM) and blocks CRF-stimulated adenylate cyclase activity in membranes prepared from rat cortex and pituitary. Systemically administered CP-154,526 antagonizes the stimulatory effects of exogenous CRF on plasma ACTH, locus coeruleus neuronal firing and startle response amplitude. Potential anxiolytic activity of CP-154,526 was revealed in a fearpotentiated startle paradigm. These data are presented in the context of clinical findings, which suggest that CRF is hypersecreted in certain pathological states. We propose that a CRF antagonist such as CP-154,526 could affirm the role of CRF in certain psychiatric diseases and may be of significant value in the treatment of these disorders.

Acoustic Stimulation↗
PubMed1996

The limitations of an iodometric aerobic assay for peroxides.

A technique recommended for the assay of lipid and other organic peroxides based on the use of a commercial color reagent (El-Saadani et al., J. Lipid Res. 30, 627-630, 1989) has the advantage over other iodometric methods of being insensitive to oxygen. Although tested so far with a limited range of peroxides, this aerobic method has found popular use with complex biological systems, such as plasma. We have examined the ability of this assay to provide accurate estimates of peroxides in H2O2, tert-butanol, and cumene hydroperoxides, and in oxidized linoleate, low-density lipoprotein, and human blood plasma. The results were compared with values obtained with an anaerobic iodometric peroxide method taken as the standard peroxide assay. We found that the published protocol gave correct peroxide values for H2O2 solutions. Correct values could also be obtained for oxidized low-density lipoprotein, provided that the incubation period was extended from 30 to 60 min. All the other peroxides tested gave much lower values than those of the standard iodometric method. Incubation at 50 degrees C to increase the velocity of the reaction for some of the slowly reacting peroxides did not improve the accuracy of the aerobic method. We recommend that the color reagent should be used as originally specified only for the assay of H2O2, or for oxidized lipoprotein with the incubation extended to 60 min.

Humans↗
PubMed1996

The significance of valine 33 as a ligand-specific epitope of transforming growth factor alpha.

Although binding of epidermal growth factor (EGF) and transforming growth factor alpha (TGFalpha) to the EGF receptor (EGFR) is mutually competitive, their binding is not identical, and their biological activities are not always equivalent. To probe for ligand-specific interactions, we have synthesized analogues of TGFalpha with modifications to the residue lying between the fourth and fifth cysteines (the "hinge"). Although this residue lies in a structurally conserved region of the protein, it is not conserved within the EGFR ligand family. Our results show that in TGFalpha there is a preference for a bulky hydrophobic hinge residue; this contrasts with EGF, for which a hydrogen bond donor functionality is preferred. Sequence analysis of the human EGFR ligands revealed that the nature of the hinge residue correlated with the sequence in the B-loop beta-sheet. As this region is an important determinant in recognition of TGFalpha by the chicken EGFR, we assessed the mitogenicity of the TGFalpha hinge mutants, as well as the other EGFR ligands, using chicken embryo fibroblasts. The preference of the chicken EGFR for TGFalpha hinge mutants with hydrophobic side chains paralleled that of the human EGFR. Betacellulin and heparin-binding EGF-like growth factor also possess an hydrophobic hinge; both were at least as potent as TGFalpha for chicken embryo fibroblasts. EGF and amphiregulin, both with hydrogen bond donor functionalities at their hinge, displayed markedly decreased in potency by comparison with TGFalpha. We propose that EGFR ligands can be subclassified into TGFalpha-like and EGF-like and that this is of functional significance, identifying a potential mechanism whereby EGFR can discriminate between its ligands.

Amino Acid Sequence↗
PubMed1996

Partial intestinal obstruction induces substantial mucosal proliferation in the pig.

Parenteral nutrition and improving supportive treatment have resulted in prolonged survival for patients with short bowel syndrome. However, definitive therapy for patients with short bowel syndrome must focus on increasing small intestinal mucosal mass. Intestinal lengthening procedures rely on intestinal dilation to accomplish this. The authors hypothesized that partial intestinal obstruction would result in consistent dilation of the intestine and would provide increased intestinal mass for use in intestinal lengthening. The authors developed a partially obstructing prosthetic valve to dilate the intestine before intestinal lengthening. This report describes the changes elicited by the valve. Twelve weanling pigs were divided randomly into two groups of six. One group had valve placement 240 cm distal to the ligament of Treitz; the other had sham surgery. The survival rate was 100% for both groups, and the mean weight gain was similar. Both groups were fed pig chow mush and were killed 5 weeks after surgery. Intestinal diameter was measured, and the small intestine was harvested, preserved, and sectioned for microscopic examination. The mean bowel diameter 15 cm proximal to the valve was 4.7 cm in the valved group and 3.3 cm in the sham group (42% increase). Total mucosal thickness, villus height, crypt depth, and villus density were significantly greater for the valved pigs in all sections (proximal and distal to the valve). Surface index and intestinal circumference were significantly greater in the valved pigs in all sections proximal to the valve, but there was no significant difference in these values for sections distal to the valve. There was no significant difference in villus cell density between the two groups at any location. Chronic partial obstruction of the small intestine results in consistent dilation of the intestine, with growth of all layers of the bowel, including the mucosa. This dilation and mucosal growth results in a true increase in surface area and is an ideal first step toward sequential lengthening.

Animals↗
PubMed1996

1996 Joseph E. Whitley, MD, Award. Evaluation of an introductory course in chest radiology.

RATIONALE AND OBJECTIVES: The author developed and evaluated the effectiveness of an educational program for teaching the fundamentals of chest radiology to radiology residents. METHODS: Nineteen radiology residents completed a course that consisted of 17 1-hour chest radiology conferences. All seven 1st-year radiology residents were required to attend every conference; more senior-level residents were encouraged to attend, but their attendance was not mandatory. All conferences were given by the same instructor with the use of a didactic slide and radiograph presentation, videotape, heart-lung model, and a 120-page syllabus. Residents were encouraged to participate in a daily quiz. Resident learning was measured by means of a pre- and postcourse examination. RESULTS: Conference attendance rate was 93% for 1st-year residents and 75% for more senior residents. Nineteen residents took both the pre- and postcourse examination; mean scores increased from 65.6% to 86.2% (P < .0001), and course evaluation scores were very positive (means ranged from 1.0 to 1.1, with 1 = very good and 5 = poor). CONCLUSION: An educational program in chest radiology was developed for residents. Both objective and subjective evaluations indicated that resident participation in the introductory chest course was an effective means of learning the basics of chest radiology. The residents were in support of making this course a required part of the residency curriculum.

Audiovisual Aids↗
PubMed1996

Resident conference at the viewbox: an experimental approach.

RATIONALE AND OBJECTIVES: To develop and test an experimental radiology resident conference format designed to incorporate more cases, improve visibility of cases, increase resident participation, decrease resident anxiety, and provide residents with feedback on their oral presentation skills. METHODS: Sixteen radiology residents were paired into eight teams. Each team was given an identical packet of eight chest radiograph cases, assigned a viewbox, and given 16 minutes to review the cases. Each case was then discussed in front of the group, by one resident from a team, such that all teams participated in oral presentation. The conference moderator provided a written handout, discussion of the findings, and diagnosis for each case. Residents anonymously evaluated each other's performance, the experimental conference format, and 15 traditional conferences. RESULTS: Residents subjectively found the experimental conference to be a statistically significant improvement over the traditional conferences in certain areas (P < .05). CONCLUSION: The experimental conference serves as a valuable alternative to the traditional "hot-seat" conference.

Educational Measurement↗
PubMed1996

A transcription map of the DiGeorge and velo-cardio-facial syndrome minimal critical region on 22q11.

The majority of patients with DiGeorge syndrome (DGS) and velo-cardio-facial syndrome (VCFS) have a microdeletion of 22q11. Using translocation breakpoints and fluorescence in situ hybridization analysis (FISH), the minimal DiGeorge critical region (MDGCR) has been narrowed to 250 kb in the vicinity of D22S75 (N25). The construction of a detailed transcription map covering the MDGCR is an essential first step toward the identification of genes important to the etiology of DGS/VCFS, two complex disorders. We have identified a minimum of 11 transcription units encoded in the MDGCR using a combination of methods including cDNA selection, RT-PCR, RACE and genomic sequencing. This approach is somewhat unique and may serve as a model for gene identification. Of the 11 transcripts, one is the previously reported DGCR2/IDD/LAN gene, and three revealed a high level of similarity to mammalian genes: a Mus musculus serine/threonine kinase, a rat tricarboxylate transport protein and a bovine clathrin heavy chain. The remaining transcripts do not demonstrate any significant homology to genes of known function. The identification of these transcription units in the MDGCR will facilitate their further characterization and help elucidate their role in the etiology of DGS/VCFS.

Abnormalities, Multiple↗
PubMed1996

The effect of adjuvant prednisone combined with CMF on patterns of relapse and occurrence of second malignancies in patients with breast cancer. International (Ludwig) Breast Cancer Study Group.

BACKGROUND: The addition of low-dose prednisone (p) to the adjuvant regimen of cyclophosphamide, methotrexate, 5-fluorouracil (CMF) allowed patients to receive a larger dose of cytotoxics when compared with those on CMF alone. However, disease-free survival and overall survival were similar for the two groups. To test the hypothesis that low-dose prednisone might influence the efficacy of the cytotoxic regimen used, the toxicity profiles of the two treatment regimens and the patterns of treatment failure (relapse, second malignancy, or death) were examined. PATIENTS AND METHODS: 491 premenopausal and perimenopausal patients with one to three positive axillary lymph nodes included in International (Ludwig) Breast Cancer Study Group (IBCSG) trial I from 1978 to 1981 and randomized to receive CMF or CMFp were analyzed for differences in long-term outcome and toxic events. The 250 patients assigned to CMF and prednisone received on the average 12% more cytotoxic drugs than those who received CMF alone. RESULTS: The 13-year DFS for the CMFp group was 49% as compared to 52% for CMF alone, and the respective OS percents were 59% and 65%. Several toxic effects such as leukopenia, alopecia, mucositis and induced amenorrhea were reported at a similar incidence in the two treatment groups. Using cumulative incidence methodology for competing risks, we detected a statistically significant increase in first relapse in the skeleton for the CMFp group at 13 years follow-up with a relative risk (RR) of 2.06 [95% confidence interval (CI), 1.23 to 3.46; P = 0.004]. Patients with larger tumors in the CMFp regimen were especially subject to this increase with a RR for failure in the skeleton of 3.32 (95% CI, 1.57 to 7.02; P = 0.0005). CMFp-treated patients also had a larger proportion of second malignancies (not breast cancer), with RR of 3.34 (95% CI, 0.91 to 12.31; P = 0.09). CONCLUSIONS: Low-dose continuous prednisone added to adjuvant CMF chemotherapy enabled the use of higher doses of cytotoxics. This increased dose had no beneficial effect on treatment outcome, but was associated with an increased risk for bone relapses and a small, not statistically significant increased incidence of second malignancies. The effects of steroids, which are widely used as antiemetics (oral or pulse injection) together with cytotoxics, should be investigated to identify their influence upon treatment outcome.

Antineoplastic Agents, Hormonal↗
PubMed1996

Current issues in multispecialty group practice: the Lahey Hitchcock Clinic merger experience.

The merger of two large not-for-profit multispecialty group practices in 1995 forced the two founding organizations into a deeper understanding of their heritage and mission. Common features of Lahey Hitchcock and similar organizations of their vintage are discussed. Issues addressed include governance, desirable leadership characteristics and growth, "incentivizing change," and workforce planning.

Governing Board↗
PubMed1996

Responsiveness of a single-item indicator versus a multi-item scale: assessment of emotional well-being in an international adjuvant breast cancer trial.

A single-item linear analogue self-assessment scale for mood was compared with a 28-item adjective checklist for emotional well-being. To confirm its concurrent validity and responsiveness to treatment and recurrence in patients with breast cancer, emotional well-being was assessed every 3 months for 2 years and at 1 and 6 months after recurrence in 1,169 patients who were premenopausal and 960 patients who were postmenopausal. These patients were enrolled in two International Breast Cancer Study Group randomized clinical trials in operable breast cancer conducted from 1986 to 1993. To assess concurrent validity, Pearson's correlation between the linear analogue self-assessment scale and the adjective checklist were calculated for each time-point within each treatment group and for the two assessments after recurrence. Responsiveness to treatment and recurrence were analyzed using paired t tests and the squared ratio of these t tests, an estimate of relative efficiency. Concurrent validity of the mood linear analogue self-assessment was consistently confirmed across four language groups. Both measures were responsive; out of 24 changes over time, 19 were in the expected direction for the linear analogue self-assessment scale (p < or = 0.05 for 9 of 19) and 17 for the adjective checklist (p < or = 0.05 for 10 of 17). The linear analogue self-assessment scale was less but significantly efficient for detection of treatment effects, with relative efficiency estimates ranging from 0.16 to 2.45 and a median of 0.66 among the comparisons with relatively stable estimates (/t/ > or = 1.0) and more efficient for recurrence than the adjective checklist. The mood linear analogue self-assessment scale is a valid indicator of emotional well-being in patients with breast cancer in large multicenter, multicultural trials in which comprehensive scales are less feasible. This investigation supports the clinical relevance of linear analogue self-assessment scales as indicators of components of quality of life in cancer clinical trials.

Adult↗
PubMed1996

Periodontal infection as a possible risk factor for preterm low birth weight.

Peridontal diseases are gram-negative anaerobic infections that can occur in women of childbearing age (18 to 34 years). In the present investigation we sought to determine whether the prevalence of maternal periodontal infection could be associated with preterm low birth weight (PLBW), controlling for known risk factors and potential covariates. A case-control study of 124 pregnant or postpartum mothers was performed. PLBW cases were defined as a mother with a birth of less than 2,500 g and one or more of the following: gestational age < 37 weeks, preterm labor (PTL), or premature rupture of membranes (PROM). Controls were normal birth weight infants (NBW). Assessments included a broad range of known obstetric risk factors, such as tobacco use, drug use, alcohol consumption, level of prenatal care, parity, genitourinary infections, and nutrition. Each subject received a periodontal examination to determine clinical attachment level. PLBW cases and primiparous PLBW cases (n = 93) had significantly worse periodontal disease than the respective NBW controls. Multivariate logistic regression models, controlling for other risk factors and covariates, demonstrated that periodontal disease is a statistically significant risk factor for PLBW with adjusted odds ratios of 7.9 and 7.5 for all PLBW cases and primiparous PLBW cases, respectively. These data indicate that periodontal diseases represent a previously unrecognized and clinically significant risk factor for preterm low birth weight as a consequence of either PTL or preterm PROM.

Adolescent↗
PubMed1996

Canuck place: a hospice for dying children.

Parents will never face a more stressful event than the news that their child will die. A child's terminal illness challenges every belief, emotion and dream that a parent has. In addition to the emotional drain, caring for a dying child is physically exhausting. Moreover, the child's illness affects the lives of all brothers, sisters, aunts, uncles and grandparents. The care of these children and their families demands a holistic program of services, including physical and emotional support, as well as tangible ways to relieve parents from the continuous 24-hour care of their child. And after the child has died, the emotional support must continue as families learn to face life without their child.

Child↗
PubMed1995

A human pancreatic secretory trypsin inhibitor presenting a hypervariable highly constrained epitope via monovalent phagemid display.

Hypervariable gene banks displaying ligands which can be used for affinity optimisation are valuable resources for examining shape space. They have added value if the ligand is small, if there is extensive information on its tertiary structure and if the variable region is highly constrained. These features would be expected to stabilise complexes by reducing the dissociation constants and to facilitate their use as 'lead substances' for the development of synthetic mimetics. The synthesis and characterisation of such phagemid-display banks is described here, in which the variable region is a 7-amino acid (aa) (pSKAN8-HyB/C) or 8-aa (pSKAN8-HyA) extended peptide held between two disulfide bridges at the exposed tip of the human pancreatic secretory trypsin inhibitor (PSTI). A phagemid pSKAN8 was created which contains a fusion between the PSTI and M13 pIII protein-coding genes. Cassettes containing the sequences (NNK)8 [HyA], (NNK)7 [HyB] or (NNK)6GTT [Hy-C] (where K = G or T) were used to randomize the aa coding region in the trypsin-inhibitory loop (aa 17 to 23) of PSTI. Some 31 million individual clones were generated in a mutS Escherichia coli strain kept as frozen cell stocks. Analysis of controls which had not undergone selection showed very low levels of deletion. The quality of the hypervariable region and bias of codon usage was quantified by DNA sequencing. It was estimated from SDS-PAGE that hybrid protein was represented statistically at a frequency of one molecule per two phagemid particles. The functionality and reproducibility of the system was demonstrated by trypsin-binding of the original vector and in selecting novel chymotrypsin inhibitors from the banks.

Amino Acid Sequence↗
PubMed1995

The role of pterins in depression and the effects of antidepressive therapy.

Urinary excretion of neopterins (N) and biopterins (B) was measured in 48 patients with depression before and after treatment with placebo, antidepressants, or electroconvulsive therapy (ECT), and in 26 healthy control subjects. Patients prior to and after treatment had a significantly greater neopterin/biopterin (N:B) ratio than control subjects. There was a significant correlation between N:B ratios and the severity of depression and plasma cortisol. As a raised N:B ratio implies failure to convert neopterin to biopterin, it is possible that reduced availability of tetrahydrobiopterin, the essential cofactor for the formation of noradrenaline, serotonin and dopamine, may exert rate-limiting control over the synthesis of monoamines implicated in the pathogenesis of depressive illness.

Adult↗