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Biomedical subjects

J L Andrews

Publications and source records attributed to J L Andrews.

At least 37 records · Page 2Linked to original sources
PubMed1996

Contraceptive use among female adolescents.

Teenage pregnancy continues to be a problem in the United States despite the availability of reliable contraceptive methods. A pilot study was conducted to determine the use of reliable contraception by teenagers following an abortion or negative pregnancy test. The results indicated that 96.6% of the teenagers experiencing a therapeutic abortion and 49.6% of the teens having a negative pregnancy test reported choosing reliable contraception after the procedure or the test. At a subsequent clinic visit, however, only 27.5% in the abortion group and 5.7% in the negative pregnancy test group reported use of reliable contraception. Further research is needed to identify factors involved in teenagers' use or nonuse of contraception.

Abortion, Legal↗
PubMed1995

Mutational spectra in the lacl gene in skin from 7,12-dimethylbenz[a]anthracene-treated and untreated transgenic mice.

Transgenic mice carrying the bacterial lacl gene in a lambda shuttle vector were used to isolate and characterize background and 7,12-dimethylbenz[a]anthracene (DMBA)-induced mutations in skin. Adult male mice were treated once topically with either DMBA or acetone or were left untreated. Seven days later, DMBA treatment had significantly increased the mutant frequency in the skin (mean +/- SEM, 36 +/- 3 x 10(-5)) versus in vehicle-treated (6.4 +/- 1.2 x 10(-5)) and untreated mice (7.1 x 1.0 x 10(-5)). At least 10 mutants from each of three DMBA-treated and three untreated mice were selected for DNA sequence analysis. In each case, the entire 1080-bp target gene was sequenced. Base-pair substitutions predominated (86 of 96 mutations), although frameshift and deletion mutations were also detected. Twelve percent of the mutants carried more than one mutation. In controls, the mutations were predominantly GC-->AT transitions (26 of 42), and no AT-->TA transversions were recovered. In contrast, in the DMBA-treated mice, AT-->TA transversions represented 42% of the mutations (23 of 54) and GC-->AT transitions accounted for only 11%. The AT-->TA transversions occurred mostly at 5'-CA sites. This class of mutation has been recovered frequently in ras genes from DMBA-treated mice and probably represents an early event in carcinogenesis (Nelson MA et al., Proc Natl Acad Sci USA 89:6398-6402, 1992). Our present results are consistent with the types of DNA damage induced by DMBA. The observation of different mutant frequencies and spectra in treated and control mice demonstrates the utility of this approach in the study of mutagenesis in vivo.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

The serine proteinase inhibitory proteins of the human intervertebral disc: their isolation, characterization and variation with ageing and degeneration.

Serine proteinase inhibitory proteins (SPIs) were extracted from human disc tissues using 2 M GuHCl and subjected to CsCl density gradient ultracentrifugation. The SPIs recovered in the low buoyant density fractions (rho < or = 1.35 g/ml) were purified by a combination of gel-permeation, ion-exchange, trypsin affinity, and reverse-phase high performance chromatographies. Characterisation of the major disc SPI by polyacrylamide gel electrophoresis, isoelectric focussing, enzyme inhibition and pH stability studies indicated that this small molecular weight (12-14 kDa), highly basic (pI > 9.5), acid-stable but alkaline-labile protein possessed potent inhibitory activity against bovine pancreatic trypsin and chymotrypsin, and human leukocyte elastase and cathepsin G. Two-major and two-minor low molecular weight cationic SPI species were identified by reverse-phase HPLC. The predominant species was identical to a human articular cartilage SPI sharing amino terminal sequence homology with the mucus proteinase inhibitors (MPIs). It also cross-reacted with an antiserum to the MPIs and behaved identically to secretory leucocyte proteinase inhibitor (SLPI) when examined by reverse phase HPLC, and SDS PAGE. A higher molecular weight (54 kDa), anionic (pI approximately 4.6) SPI was also purified and identified as alpha 1-proteinase inhibitor (alpha 1-PI). Quantification of alpha 1-PI and the small molecular weight cationic disc inhibitors indicated that the latter were depleted in morphologically degenerate disc tissues while levels of alpha 1-PI were somewhat higher although a large proportion of the alpha 1-PI was inactive. A depletion of total SPI levels was evident overall in degenerate discs suggesting a functional role for these inhibitory proteins in the maintenance of IVD matrix homeostasis.

Adolescent↗
PubMed1992

A comparative study of the low-molecular mass serine proteinase inhibitors of human connective tissues.

Low molecular mass serine proteinase inhibitors isolated from human articular cartilage, intervertebral disc, meniscus, and costal cartilage were compared chromatographically. Similar charge and size properties were exhibited when these inhibitors were examined by gel permeation and cation exchange chromatography. The individual proteinase inhibitory species separated by these procedures all cross-reacted with a polyclonal antibody raised against the mucous proteinase inhibitors (MPIs) obtained from human bronchial secretions, however the distribution of these MPI-like species varied with the origin of the connective tissue. The major inhibitory species present in human articular cartilage and intervertebral disc were purified to homogeneity using gel filtration, cation exchange, trypsin affinity and high performance reverse phase chromatography. The amino-terminal sequences of the purified cartilage intervertebral disc inhibitors was found to be identical to the published sequence of MPIs isolated from parotid and seminal secretions. These findings indicate that the endogenous small molecular mass cationic serine proteinase inhibitory proteins present in human cartilaginous connective tissues are members of the MPI family of proteinase inhibitors.

Amino Acid Sequence↗
PubMed1991

Tumor necrosis factor (TNF) receptor expression in T lymphocytes. Differential regulation of the type I TNF receptor during activation of resting and effector T cells.

The expression of TNF-alpha receptors (TNFR) was examined on a CD4+ T cell hybridoma, transformed T cell lines, CTL clones, and activated T cells from peripheral blood to determine the basis of the immunomodulatory activity of TNF on T cell function. Analyses by ligand cross-linking and competitive binding assays with mAb to the 80-kDa receptor (TNFR-I), demonstrated that the TNFR-I was the predominant receptor expressed on activated CD4+ and CD8+ T cell subsets. However, on T cell leukemic lines, a second, non-TNFR-I binding site was identified, most likely the 55-kDa form (TNFR-II). Additional subsets of T cells were readily distinguished by their expression of TNFR-I and related members of the TNFR gene family (CD40 and CD27). Expression of the TNFR-I was dependent upon the state of T cell activation. Signaling through the TCR for Ag or IL-2R was sufficient to induce TNFR mRNA and protein expression in resting T cells. Multiple sizes of TNFR-I transcripts were detected during T cell activation; however, biosynthetic studies showed these multiple species encode a single protein of 80 kDa. These results, combined with the known ability of TNF to induce IL-2R expression, indicate that TNF and IL-2 form a reciprocating receptor amplification circuit. In contrast, differentiated effector T cells triggered through the TCR or protein kinase C initiated a rapid down-regulation (transmodulation) of the TNFR-I that preceded TNF or lymphotoxin secretion. The mechanism of transmodulation involved proteolytic processing of the mature 80-kDa receptor releasing a soluble 40-kDa fragment. This indicates that a TNF autocrine loop is not likely to form during the response of an effector T cell. Collectively, these results suggest that transcriptional and post-translational modification of the TNFR-I are important control points regulating the expression of this receptor during T cell activation.

Animals↗
PubMed1990

Low molecular weight serine proteinase inhibitors of human articular cartilage. Isolation, characterization, and biosynthesis.

The major low molecular weight serine proteinase inhibitor of human articular cartilage was purified to homogeneity as determined by single-peak elution with 4 high resolution techniques. The purified protein was found to be a potent inhibitor of human leukocyte elastase and cathepsin G, as well as the native serine proteinases derived from human articular cartilage and intervertebral disc. The inhibitor and lysozymes were synthesized by human articular cartilage in vitro. These properties and the ability of this cationic inhibitor to bind to cartilage matrix components suggest a possible role in the modulation of matrix catabolism in normal and pathologic states.

Amino Acids↗
PubMed1987

Magnetic resonance imaging in the diagnosis of the cranio-cervical manifestations of the mucopolysaccharidoses.

Sixteen magnetic resonance (MR) studies were performed in eight patients with mucopolysaccharidosis (MPS). In patients with Hunter, Hurler, and Scheie syndromes, multiple areas of increased signal intensity were noted in the periventricular white matter. Computerized tomography (CT) frequently failed to demonstrate these white matter lesions. Other findings included spinal cord compression, hydrocephalus and airway obstruction due to soft tissue thickening around pharynx. In patients with Morquio syndrome, cervical spine dislocation, spinal cord compression and hydrocephalus were diagnosed by MR. MR was superior compared to CT, plain films and plain tomography, as the narrowing caused by bone and soft tissue changes were better seen with MR. Our experience suggests that MR should be the primary imaging modality for the detection of cranial abnormalities in patients with MPS. High resolution surface coil imaging may be preferable to invasive procedures such as myelography and CT with intrathecal contrast agents for the evaluation of cervical spine disease.

Adolescent↗
PubMed1986

Variation with ageing and degeneration of the serine and cysteine proteinase inhibitors of human articular cartilage.

The proteoglycans, and proteinase inhibitors of normal and degenerate human articular cartilage have been isolated by 4.0M GuHCl extraction, CsCl density gradient ultracentrifugation and Sephadex G-75 gel filtration chromatography. While a small amount of trypsin inhibitory activity eluted in the Sephadex G-75 void volume, the major proteinase inhibitors were included in the column with MWs within the range 1 - 3 X 10(4) daltons. The large molecular weight trypsin inhibitor was identified as alpha 1-trypsin inhibitor, which was present in greater amounts in degenerate tissue. The Sephadex G75 included fractions (LMWCI) showed inhibition against cysteine and serine proteinases and were reduced in degenerate tissue, but slightly elevated in aged "normal" cartilage. We suggest that the resistance of ageing cartilage to enzymatic degradation may be related to the levels of LMWCI within these tissues.

Aged↗
PubMed1985

Lung cancer in women. Lahey Clinic experience, 1957-1980.

The incidence of lung cancer is increasing dramatically worldwide. Cancer of the lung, the number one cause of death from cancer in men in the United States, will soon surpass breast cancer to become the most frequent cause of cancer death in women. To detail the changing pattern of lung cancer, we reviewed the clinical features of all 1752 patients whose lung cancer was diagnosed at the Lahey Clinic from 1957 through 1980. Women comprised a constant proportion of the total number of clinic patients during this 24-year period. Lung cancer in women increased markedly from 13% of all patients (1 to 6.8 ratio of women to men) in 1957 through 1960 to 35% (1 to 1.8 ratio) in 1977 through 1980. The authors reviewed pathologic specimens of 394 women with lung cancer. No significant change occurred in cell type distribution over the years: adenocarcinoma, 38%; epidermoid carcinoma, 20%; large cell carcinoma, 15%; small cell undifferentiated tumor, 13%; and other cell types, 14%. The incidence of all lung cancer cell types (Kreyberg Group 1 and Group 2) increased in women who smoked. Our study suggests that smoking is a major causal factor in the rising occurrence of all lung cancer cell types in women as contrasted to the preponderance of Kreyberg Group 1 tumors in men who smoke.

Adenocarcinoma↗
PubMed1985

Distribution and binding of glycosaminoglycan polysulfate to intervertebral disc, knee joint articular cartilage and meniscus.

The relative incorporation of 3H-Glycosaminoglycan polysulfate (3H-GP, Arteparon) into rabbit knee joint articular cartilage, patella cartilage, meniscus and intervertebral disc tissues was determined at 1, 2, 4 and 8 d after intramuscular administration (60 muCi/kg, 400 micrograms/kg). The distribution of the drug within these tissues was also examined autoradiographically. The highest uptake of 3H-GP occurred in the menisci and was observed to be largely localised about collagen fibres on the outer periphery of these tissues. Over the eight day period, the level present declined to approximately 50% of that present on day one. The level of drug attained in articular and patella cartilages was approximately 20-25% of that in the meniscus. It was uniformly dispersed and remained fairly constant over the eight day period. Of greatest interest was the finding for the disc, where the highest level of labelling, which occurred on day two, was comparable to the knee joint hyaline cartilages and was associated with the collagenous lamella structure of the outer annulus fibrosus. After day two, the level of drug in these areas declined, accompanied by an accumulation in the nucleus pulposus. Using an ion exchange assay technique, and gel permeation chromatography of 4M guanidine hydrochloride extracts of these connective tissues, binding of 3H-GP to proteoglycans, collagen and non-collagenous proteins, was demonstrated; the latter component representing the major drug binding species. It is suggested that localisation of the drug within these connective tissues may be beneficial in protecting their matrix components against enzymatic degradation in the pathological state.

Animals↗
PubMed1983

The interaction of pentosan polysulphate (SP54) with human neutrophil elastase and connective tissue matrix components.

The binding of pentosan polysulphate (SP54) to human polymorphonuclear leucocyte elastase (PMNE) and some of its natural and synthetic substrates has been investigated. Using an ion exchange (DE52) assay system the binding of SP54 to PMNE was found to be 100 times stronger than to collagen or proteoglycan (PG). While the order for in vitro binding of the drug to purified substrates was found to be PG greater than gelatin greater than type I collagen, in vivo experiments indicated that SP54 was localized in tissues rich in collagen. Using gel-exclusion chromatography it was shown that these tissues also contained proteinaceous components other than PG and collagen which interacted with SP54. These results indicate that the potent inhibitor activity of SP54 against PMNE (50% inhibition at 1.7 X 10(-7)M) probably occurs by a specific interaction with the enzyme rather than by substrate binding inhibition, although the latter interaction may be important for localising the drug in these tissues.

Cartilage, Articular↗
PubMed1983

Reducing smoking in the hospital. An effective model program.

With the epidemic rise in smoking-related illnesses has come the realization that medical institutions should help prevent these diseases, as well as reduce secondhand smoke. Toward this end a comprehensive policy regarding smoking has been implemented in our 489-bed teaching hospital since 1977. Features of this program are policy formation, implementation, and follow-up by a smoking policy committee with hospital-wide representation; no smoking in most areas of the hospital (smoking permitted only in specifically designated areas); no cigarettes sold in the hospital; widespread publicity about health effects of smoking and about the policy through signs, articles, and displays; and clinics for smoking cessation. A follow-up questionnaire given to and answered by 965 of 2,700 hospital staff members 20 months after the start of the smoking policy showed that 93 percent of nonsmokers and 83 percent of smokers approved of the hospital's policy to reduce smoking; 26 percent of the previous smokers queried had quit during that time, and 33 percent of persistent smokers were smoking less. An effective comprehensive hospital-wide policy regarding smoking has reduced smoking by both staff and patients.

Boston↗
PubMed1981

Pulmonary toxicity of antineoplastic drugs.

Pulmonary toxicity caused by antineoplastic drugs is becoming a more frequently recognized entity, and the number of drugs known or suspected of causing this disease is steadily increasing. In general, the initial clinical appearance includes both constitutional signs of malaise and fever, as well as pulmonary complaints. Some clinical signs may suggest a particular drug as the cause. The pathological condition also is generally nonspecific, but some clues may be present histologically that help define the causal agent. This is a review of the antineoplastic drugs that are associated with pulmonary toxicity. Clinical, laboratory, and pathological data are presented as useful information for practicing physicians. Although therapeutic maneuvers are limited, these are discussed with regard to each drug.

Alkylating Agents↗
PubMed1981

Arterial blood gas standards for healthy young nonsmoking subjects.

Arterial blood gas analysis has become indispensable for precise physiologic assessment of many lung and heart conditions. Previous studies have related the level of arterial oxygenation to age, smoking habits, and the severity of lung or heart dysfunction. However, no study has reported complete normal blood gas values under all conditions most commonly used by cardiopulmonary laboratories to assess patients. Therefore, we assessed blood gas values in 20 nonsmoking volunteers (ten men, ten women) between 20 and 28 years of age who were healthy (negative heart-lung history and normal results on physical examination, chest radiography, and lung function testing). Blood samples were drawn from the radial artery and measured immediately on a blood gas analyzer. The findings were no significant different (P less than 0.05) in blood gas values among rest (supine), rest (sitting), and exercise (supine) conditions within sex groups; significantly lower mean PCO2 for women than for men under all conditions (except for subjects breathing 100% O2), and a higher pH for women in the rest (supine) position than under other conditions; and a lower mean PCO2 and higher pH for both groups breathing 100% O2. This study provides valid normal arterial blood gas reference standards for routine cardiopulmonary function testing.

Adult↗