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Biomedical subjects

J Woods

Publications and source records attributed to J Woods.

At least 19 recordsLinked to original sources

New anti-lung-cancer antibody cluster 12 reacts with human folate receptors present on adenocarcinoma.

Human folate receptor (hFR, folate-binding protein) is a single-chain glycoprotein with high specific affinity for folic acid and methotrexate. We have created 4 monoclonal antibodies (MAbs) to hFR, all of which react specifically with purified hFR in Western blots. Flow cytometry indicated that the antibodies all had patterns of reactivity against epithelial cell lines similar to that of antibody MW207 (workshop antibody 12), labeling 2 breast-tumor cell lines and 2 of 5 SCLC without labeling the one non-small-cell carcinoma tested. We used the antibodies to trace the in situ distribution of hFR in histologically normal tissues and in lung tumors by a sensitive alkaline-phosphatase-anti-alkaline-phosphatase immunohistochemical technique. In frozen sections of normal lung, hFR was diffusely distributed on cell membranes of type-1 and type-2 pneumocytes and mucociliary and basilar respiratory epithelial cells of distal bronchi. The receptor was focally expressed by mucociliary cells of proximal respiratory mucosa and by macrophages, but was not detected in stromal smooth muscle, fibroblasts or lymphoid cells. In tumors, hFR was heavily and diffusely expressed on cell membranes of 9 of 10 pulmonary adenocarcinomas, 5 of 5 bronchioloalveolar carcinomas and 2 of 2 carcinoid tumors. It was focally expressed in 3 of 5 large-cell lung carcinomas and was absent from 4 of 5 small-cell carcinomas, 18 of 22 invasive squamous carcinomas, 2 of 2 in situ squamous carcinomas, and 13 of 13 squamous dysplasias of bronchial mucosa. We conclude that hFR is heavily expressed in situ by normal alveolar and bronchial epithelium and by adenocarcinoma of lung. It is usually absent from small-cell carcinoma and squamous tumors at levels detectable by immunohistochemistry.

Adenocarcinoma

Topical tretinoin improves the appearance of photo damaged skin.

A multicentre clinical trial has been conducted to assess the efficacy and safety of tretinoin 0.05% cream (Retin-A) in the treatment of photo-damaged Australian skin. Subjects with cutaneous facial photodamage were randomised to treatment with tretinoin (62) or vehicle (63) cream. After an initial two week run-in, all subjects applied the cream to the face, neck and left forearm/hand, once nightly for 24 weeks. Changes in clinical signs of photodamage and parameters of cutaneous irritation were assessed by investigators using a 7 point scale, whilst changes in signs of photodamage were rated by subjects using a 5 point scale. Changes in skin biopsies and silicone skin surface replicas were also assessed. Significant improvements in skin wrinkles, mottled hyperpigmentation, laxity, lentigines and roughness of tretinoin treated subjects were noted by investigators. Subjects receiving tretinoin noted significant improvements in skin wrinkles, tightness, colour and pores. Improvement in overall severity of photodamage was significantly greater for tretinoin treated subjects and was progressive over the study period. Histological findings included a significant increase in mean epidermal thickness. Significant topographical changes were not detected in skin surface replica sets. Cutaneous irritation, the most common side effect, was usually mild and transient. We conclude that tretinoin 0.05% cream significantly improved the appearance of photo-damaged skin.

Administration, Cutaneous

Effect of training and growth hormone suppression on insulin-like growth factor I mRNA in young rats.

The growth hormone (GH)-insulin-like growth factor I (IGF-I) axis plays a role in the adaptation to exercise training, but IGF-I gene expression in response to exercise training and GH suppression has not been studied. Twenty female rates underwent a 4-wk treadmill training program begun in the prepubertal period (day 14 of life). In 10 of the training rats, GH production was suppressed by anti-GH-releasing hormone antibodies (GH suppressed). IGF-I mRNA and protein levels were measured in liver and hindlimb skeletal muscle. GH suppression reduced IGF-I mRNA expression in the liver to a much greater extent than in the muscle. In the GH control rats, training induced significant increases in hepatic exon 1-derived IGF-I mRNA (mean increase 30%; P < 0.05) and muscle exon 2-derived mRNA (mean increase 35%; P < 0.05). In the GH-suppressed rats, only muscle exon 1-derived transcripts were significantly increased by training (55%; P < 0.05) and this was associated with a significant increase in muscle IGF-I protein levels (P < 0.05). We speculate that the anabolic response to training may involve both GH-dependent increases in IGF-I mRNA in the liver and GH-independent increases in the muscle.

Actins

Aggression and fighting behavior among African-American adolescents: individual and family factors.

OBJECTIVES: This study examined the extent to which individual and family factors are associated with aggression and fighting behavior among African-American middle school adolescents. METHODS: Four hundred thirty-six African-American boys and girls from two middle schools in a predominantly low-income North Carolina school system were surveyed and their school records examined. Information was collected concerning students' aggression levels, school fighting behavior, school suspensions for fighting, attitudes toward violence, perceptions of their families' attitudes toward violence, weapon-carrying behavior, and sociodemographics. Multivariate analyses were employed to predict the students' aggression levels, fighting behavior, and school suspensions. RESULTS: Factors related to the individual adolescents, such as gender, age, weapon-carrying behavior, and attitudes toward violence, were associated with students' reports of aggression and fighting behavior. Factors related to family and school were associated with school suspension for fighting. CONCLUSIONS: This study suggests that violence prevention programs set in our elementary and middle schools may reduce aggression and fighting among our youth. School teachers and public health practitioners are encouraged to work together in understanding and preventing adolescent violence.

Adolescent

Coupling of GTP-binding to the T cell receptor (TCR) zeta-chain with TCR-mediated signal transduction.

The zeta-subunit of the TCR binds GTP and is a well characterized substrate for a TCR-activated tyrosine kinase. To examine the possible coupling of GTP-binding to zeta with TCR-mediated signal transduction, a mutant (termed J32-3.2) of the T cell line Jurkat (J32) was used. Anti-TCR/CD3 stimulation of the TCR/CD3+ J32-3.2 cells resulted in a weak stimulation of both the phosphatidyl inositol and tyrosine kinase signal transduction pathways, as measured by changes in the level of free intracellular calcium, tyrosine phosphorylation of TCR-zeta, CD3-epsilon and ZAP-70, p56lck, or p59fyn tyrosine kinase activity and IL-2 gene activation. The impaired responsiveness of J32-3.2 cells to anti-TCR/CD3 mAb correlated with a low basal level of GTP-binding to zeta. Furthermore, in J32-3.2 cells TCR activation by antibody ligation caused a weaker increase in GTP-binding to the zeta-chain, as compared with that of wild-type J32 cells, which indicates for the first time that GTP-binding to zeta can be modulated by extracellular signals and suggest that the role of GTP-binding to zeta is to couple the TCR to intracellular signal transduction mechanisms.

Amino Acid Sequence

MAMBAs: a real-time graphics environment for QSAR.

MAMBAs (Multivariate Analysis Methods in Biomechanistic Activity Studies) is an integrated workstation-based graphics program designed for the investigation of quantitative structure activity relationships (QSAR). It combines many of the commonly used statistical techniques with an extensive database of substituent constants, a variety of molecular and substituent property calculations and detailed graphics-based table and graph editors. Graphical representations of standard substituent generation and optimization techniques are also included. These are all utilized within a state-of-the-art real-time graphics environment.

Computer Graphics

Social intervention against AIDS among injecting drug users.

Many drug injectors continue to engage in behaviors that lead them to become infected with HIV in spite of a wide variety of public health programs. In addition, many persons have begun to inject drugs in spite of knowing the risks of AIDS. The inadequacy of current efforts to prevent these behaviors suggests that additional forms of intervention should be attempted. We suggest that social interventions be tried to complement current programs (almost all of which have an individual focus). Evidence that social factors such as peer pressure and the social relations of race affect risk behavior is presented. Social interventions that are discussed include organizing drug injectors against AIDS in ways analogous to those in which gays organized against the epidemic, and finding ways to change large-scale social relationships that predispose people to inject drugs.

Acquired Immunodeficiency Syndrome

Hemodynamic evaluation of the Monostrut and spherical disc Björk-Shiley aortic valve prosthesis with Doppler echocardiography.

A Doppler echocardiographic study was performed to assess whether the Monostrut model of the Björk-Shiley valve (Shiley, Inc., Irvine, Calif.) had an improved hemodynamic performance in comparison with the spherical disc model in the aortic position. Twenty retrospectively randomly selected patients were studied, 10 with each valve type. Within each valve type two sizes of valve were studied, 21 and 23 mm. The two groups were comparable with respect to age, postoperative time, fractional shortening, New York Heart Association functional class preoperatively, and body surface area. Pulsed and continuous wave Doppler measurements were recorded at rest. Continuous wave Doppler recordings were performed every 2 minutes after exercise with supine bicycle ergometry until 10 minutes after exercise. Peak and mean gradients across the aortic valve prostheses were estimated. Both groups achieved a significant and comparable rise in heart rate with exercise. The mean gradients +/- standard error of the mean at rest and 2 minutes after exercise were 19.7 +/- 1.9 mm Hg and 30.9 +/- 2.2 mm Hg, respectively in the spherical disc group compared with 14.9 +/- 1.1 mm Hg and 23.6 +/- 1.7 mm Hg in the Monostrut group (p < 0.05 and p < 0.025, respectively). Peak transvalvular gradient at rest was 30.7 +/- 2.7 mm Hg in the spherical group compared with 23.9 +/- 1.9 mm Hg in the Monostrut group (p < 0.05). We conclude that the Monostrut Björk-Shiley valve prosthesis has better hemodynamic performance than the spherical disc model in the aortic position.

Aortic Valve

Rehabilitation in chronic back pain: employment status after four years.

Of 129 chronic back pain patients treated consecutively at the Palmerston North hospital rehabilitation unit in 1982-3, 102 responded to a questionnaire in 1987. The 27 nonresponders had had pain for a shorter time and were considered to have a better prognosis. Of the 102 responders, 31 no longer had back pain; 51 (six women) were employed full or part time and 17 (two women) were looking for work. Two men had reversed roles and 17 had retired. Women who no longer had a job outside the home classed themselves as housewives rather than as retired or unemployed. This study provides data for future planning but without controls, confident conclusions cannot be drawn on the efficacy of the rehabilitation programme. There is a need for further controlled studies.

Adolescent

Effects of time of insemination relative to ovulation on pregnancy rate and embryonic-loss rate in mares.

The effects of pre-ovulatory and post ovulatory insemination on pregnancy rate and embryonic-loss rate were studied in 268 mares in two experiments. Within each experiment mares were randomised within replicates as follows: to be inseminated on the day the pre-ovulatory follicle reached 35 mm (pre-ovulatory group), to be inseminated on the day of ovulation (Day 0 group), and to be inseminated on the day after ovulation (Day 1 group). Ultrasonic pregnancy diagnoses were performed on Days 11, 12, 13 and 14 (Experiment 1) and Days 11, 12, 13, 14, 15, 20 and 40 (Experiment 2). Combined for the two experiments, pregnancy rates were different (P less than 0.01) among the three groups. For Experiment 2, pregnancy rate within the pre-ovulatory group was lower (P less than 0.05) for insemination 4 days or more before ovulation than for up to 3 days before ovulation. Pregnancy rate was lower (P less than 0.05) for the Day 0 group than for the pre-ovulatory group inseminated up to 3 days before ovulation. In Experiment 2, ovulation was detected by examinations every 6 h; pregnancy rate was greater (P less than 0.05) for mares inseminated 0 to 6 h after ovulation than for mares inseminated at 18 to 24 h. No pregnancies occurred when mares were inseminated 30 h or more after ovulation. The mean day of first detection of the embryonic vesicle was different (P less than 0.0001) among the three groups. Diameter of embryonic vesicle averaged over Days 11 to 15 also differed (P less than 0.0001) among groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

AIDS and the social relations of intravenous drug users.

Gauging the impact of AIDS on intravenous drug users requires analysis of the cultural, political, and racial contexts of American society in which drug use is embedded. Considerable variation in behavior among drug injectors and noninjectors in different cities over time further complicates an understanding of the dynamics of drug use. AIDS has prompted many IV drug users to change their behavior, though not all users have reduced the risks of transmitting HIV infection. While expanded harm-reduction strategies and drug abuse treatment systems may help limit the epidemic's spread, weak federal support, constrained hospital resources, and racial stigma inhibit more direct action needed to stem the negative social and personal consequences of drug use.

Acquired Immunodeficiency Syndrome

Modulation of transferrin receptor expression and function by anti-transferrin receptor antibodies and antibody fragments.

It has been suggested that effects of anti-transferrin receptor antibodies on cell growth and receptor expression are the result of varying degrees of receptor crosslinking by bi- and multivalet binding agents. In order to study this question directly, we have cultured murine lymphoma cells in mono- and divalent fragments from IgG and IgM monoclonal anti-transferrin receptor antibodies and in intact antibodies. The studies presented here demonstrate that effects of antibody binding on transferrin receptor distribution, metabolism, and function depend, at least in part, on antibody valence, and therefore on the degree of crosslinking of receptors by antibody. We found that monovalent antibody fragments did not significantly alter cell growth, receptor surface expression, intracellular localization, or degradation. Diavalent antibody caused a uniform down-regulation of cell-surface receptor expression, which was accompanied by increased degradation only when antibody Fc was present. Normal receptor cycling apparently continued, despite the reduction in surface expression. Culture in multivalent IgM antibody, however, resulted in accumulation of antibody-complexed receptor on the cell surface without internalization and caused profound inhibition of cell growth. Thus, we show two mechanisms by which different degrees of antibody crosslinking can influence transferrin receptor function: by receptor down-regulation and blocking internalization.

Animals

The role of lithotripsy and its side effects.

The relative roles of extracorporeal shock wave lithotripsy and percutaneous nephrostolithotomy currently are being debated. Both treatment modalities are applicable to most upper urinary tract calculi. However, there are some important distinctions between the 2 techniques. Over-all, extra-corporeal shock wave lithotripsy is associated with significantly lower morbidity than percutaneous nephrostolithotomy but stone-free rates are lower for extracorporeal shock wave lithotripsy than for percutaneous nephrostolithotomy. This difference is slight for kidneys containing minimal stone burden but increases in direct proportion to increasing stone burden. The morbidity of extracorporeal shock wave lithotripsy also increases with increasing stone burden. When applied to the treatment of staghorn calculi the morbidity of both techniques is comparable but the stone-free rates are significantly better with percutaneous nephrostolithotomy. Treatment with extracorporeal shock wave lithotripsy produces changes in the kidney similar to that of renal trauma, consisting primarily of intraparenchymal and perirenal hemorrhage and edema. While the acute effects of extracorporeal shock wave lithotripsy are well tolerated by most patients, the long-term sequela of this form of therapy is not well established. Potential long-term adverse effects reported include loss of renal function, hypertension and an increased rate of new stone occurrence. The effect of shock waves on renal parenchyma in experimental animals is dose-dependent (number of shock waves). Magnetic resonance imaging of patients treated with extracorporeal shock wave lithotripsy demonstrates morphological abnormalities in or around the kidney in 63 to 85 per cent of the cases (average number of shock waves 1,200). Despite these observations the safe limits of extracorporeal shock wave lithotripsy in humans have yet to be established. Further study regarding this issue and the potential long-term adverse effects of extracorporeal shock wave lithotripsy is needed urgently.

Humans

Diagnostic value of liver biopsy in alcoholic liver disease.

Because it remains debatable whether all patients with a clinical diagnosis of alcoholic liver disease should have a liver biopsy to help confirm the diagnosis, we evaluated the diagnostic value of liver biopsy in alcoholic liver disease. Studied were 108 consecutive patients who had a percutaneous liver biopsy for the first time. In all cases the patient's clinical diagnosis recorded before biopsy was compared with the histological diagnosis of an experienced histopathologist. Prebiopsy clinical data (reported alcohol intake, signs of chronic liver disease) and laboratory data (liver function tests, mean corpuscular volume, ferritin, hepatitis B serology) were reviewed. We found that a prebiopsy clinical diagnosis of alcoholic liver disease (n = 35) was confirmed by biopsy in all but one case. The prebiopsy diagnosis of alcoholic liver disease was significantly associated with a histological diagnosis of alcoholic liver disease (specificity 98%, sensitivity 79%). Individually, alcohol intake, signs of chronic liver disease, the alanine aminotransferase (ALT), the aspartate aminotransferase to ALT ratio, and the mean corpuscular volume were significantly associated with a histological diagnosis of alcoholic liver disease. When clinical and laboratory parameters were considered jointly using stepwise logistic regression, only reported alcohol intake and mean corpuscular volume were significant. Liver biopsy may not always be necessary for the identification of that broad group of patients with alcoholic liver disease.

Alanine Transaminase

Human eosinophils have prolonged survival, enhanced functional properties, and become hypodense when exposed to human interleukin 3.

Human eosinophils were cultured in the presence of recombinant human IL-3 for up to 14 d and their biochemical, functional, and density properties were assessed. After 3 d of culture in 10 pM IL-3, eosinophils had a viability of 70% compared with only 10% in enriched medium alone. Neither IL-1 alpha, IL-2, IL-4, tumor necrosis factor, basic fibroblast growth factor, nor platelet-derived growth factor maintained eosinophil viability. The 7- and 14-d survival of the cultured eosinophils was 55 and 53%, respectively. No other cell type, including neutrophils, was present after culture. After 7 d of culture, the normodense eosinophils were converted to hypodense cells as assessed by density centrifugation. Eosinophils exposed to 1,000 pM IL-3 for 30 min or cultured in 10 pM IL-3 for 7 d generated approximately threefold more leukotriene C4 (LTC4) in response to calcium ionophore than freshly isolated cells. Furthermore, whereas freshly isolated eosinophils killed only 14% of the antibody-coated Schistosoma mansoni larvae, these eosinophils killed 54% of the larvae when exposed to 100 pM IL-3. The enhanced helminth cytotoxicity was maintained for 7 d when eosinophils were cultured in the presence of both 10 pM IL-3 and 3T3 fibroblasts, but not when eosinophils were cultured in the presence of IL-3 alone. IL-3 thus maintains the viability of eosinophils in vitro, augments the calcium ionophore-induced generation of LTC4, enhances cytotoxicity against antibody-sensitized helminths, and induces the eosinophils to become hypodense cells. These phenotypic changes in the eosinophil may be advantageous to host defense against helminthic infections but may be disadvantageous in conditions such as allergic disease.

Animals