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Biomedical subjects

K Thompson

Publications and source records attributed to K Thompson.

At least 73 records · Page 4Linked to original sources

Coping strategies and psychiatric morbidity in women attending breast assessment clinics.

This study examined the role of coping strategies and personality characteristics in mediating psychiatric morbidity in subjects facing possibly serious breast disease. Participating were 121 women aged 20 to 65 undergoing breast fine needle biopsy for a suspicious lesion on mammography. All subjects received psychosocial assessments including the 12-item General Health Questionnaire (GHQ-12), the Eysenck Personality Inventory (EPI) and the Coping Strategies Inventory. The results show that neuroticism was the only EPI subscore significantly correlated with GHQ-12 score. A habitual method of coping with adversity known as 'engagement' has a negative correlation with GHQ-12 score; that is, patients who actively confront their illness and the uncertainty that surrounds it show better psychological health. Stepwise multiple regression reveals that neuroticism and an engagement coping strategy are the most significant predictors towards GHQ-12 score prior to the diagnosis of breast cancer.

Adaptation, Psychological↗

DNA-based immunization by in vivo transfection of dendritic cells.

Delivery of antigen in a manner that induces effective, antigen-specific immunity is a critical challenge in vaccine design. Optimal antigen presentation is mediated by professional antigen-presenting cells (APCs) capable of taking up, processing and presenting antigen to T cells in the context of costimulatory signals required for T-cell activation. Developing immunization strategies to optimize antigen presentation by dendritic cells, the most potent APCs, is a rational approach to vaccine design. Here we show that cutaneous genetic immunization with naked DNA results in potent, antigen-specific, cytotoxic T lymphocyte-mediated protective tumor immunity. This method of immunization results in the transfection of skin-derived dendritic cells, which localize in the draining lymph nodes. These observations provide a basis for further development of DNA-based vaccines and demonstrate the feasibility of genetically engineering dendritic cells in vivo.

Amino Acid Sequence↗

The pharmacokinetics, antigenicity, and fusion-inhibition activity of RSHZ19, a humanized monoclonal antibody to respiratory syncytial virus, in healthy volunteers.

Single ascending doses of RSHZ19 (also known as SB 209763), a humanized monoclonal antibody (MAb) directed to the fusion protein of respiratory syncytial virus, were administered to healthy men to evaluate the safety, pharmacokinetics, antigenicity, and fusion inhibition (FI) activity of RSHZ19. Doses of RSHZ19 (0.025-10.0 mg/kg) or placebo were infused over 30 min, and subjects were followed for 10 weeks. Plasma concentrations of RSHZ19 and RSHZ19-specific antibodies were determined by ELISAs. FI titers were used to evaluate the ability of plasma to inhibit virus-induced fusion of VERO cells previously infected with RS Long strain virus. Twenty-six subjects, mean age 24, completed the study. RSHZ19 was safe and well tolerated, and no subject developed antibodies to RSHZ19 during follow-up. RSHZ19 had low plasma clearance and a half-life of approximately 23 days, similar to native IgG. Increases in FI titers relative to pretreatment levels were seen 24 h after MAb administration in all 4 subjects given 10 mg/kg and in 2 of 4 given 5 mg/kg.

Adolescent↗

Estrogen blocks early T cell development in the thymus.

PROBLEM: Pregnancy and estrogen are known to suppress B lymphopoiesis as well as lead to thymic involution in the mouse. Additionally, estrogen deficiency by oophorectomy reportedly causes a selective increase in the B220+ B cells in the murine bone marrow. The purpose of this study was to determine if estrogens played a regulatory role in T cell development. METHODS: The first experimental group consisted of 5-6-week-old Balb/c mice that received subcutaneous pellets of placebo, estriol, estradiol, or progesterone. The thymus glands were examined 2-4 weeks after treatment. The second group consisted of 6-week-old Balb/c mice who underwent either bilateral oophorectomy or a sham procedure. Two weeks after the surgery, extensive phenotypic characterization of the thymus and spleen cells was performed by flow cytometry using monoclonal antibodies to surface markers of T cell subsets. RESULTS: Estrogen treatment causes a dramatic reduction of thymic size and cellularity. All defined T cell subsets of CD4 and CD8 were reduced, with a disproportionate loss of CD4+CD8+ double positive cells. Examination of the triple negative (CD3-CD4-CD8-) subset revealed a striking loss of TN developmental progression of the early precursor cells. Based on the expression of CD44 (pgp-1) and CD25 (IL-2R alpha) markers, the TN thymic compartment was composed almost entirely of the earliest population (CD44+, CD25-), with the remaining maturational stages (CD44+, CD25+; CD44-, CD25+; CD44-, CD25-) depleted. In contrast, all T cell developmental stages in the thymus were found to be in normal proportions in the oophorectomized mice, with no differences in the splenic T and B cell subsets. CONCLUSIONS: The study demonstrates that estrogen but not progesterone blocks T cell development in the thymus. However, contrary to our expectation, estrogen deprivation by oophorectomy does not enhance T cell development.

Animals↗

Silent iritis in treated bacillary negative leprosy.

Iridectomy specimens from 59 leprosy patients who had adequate medical records of whom 33 belong to the lepromatous (LL) leprosy variety and 16 normal controls were studied histopathologically. All patients were bacteriologically negative and had received dapsone followed by multidrug therapy (MDT), or MDT only, or only dapsone for varying periods. It was found that leprosy, particularly lepromatous disease, did not significantly decrease the age of formation of cataract. Of the 33 LL patients studied 60.6% had silent iritis. The duration of treatment had no obvious influence on the persistence of iritis. Treatment with only 2 years of MDT for LL patients did not significantly increase the prevalence of persistent silent iritis compared to those who received other types of antileprosy therapy for long periods. It is pointed out that chronic iritis is a serious complication that continues even after the patient is declared clinically and bacteriologically cured, especially in patients who had a history of chronic iritis clinically.

Aged↗

Discriminative stimulus effects of butorphanol: influence of training dose on the substitution patterns produced by Mu, Kappa and Delta opioid agonists.

The discriminative stimulus effects of butorphanol were examined in separate groups of pigeons trained to discriminate either a low (0.1 mg/kg), medium (1.0 mg/kg) or high (5.6 mg/kg) dose of butorphanol from saline. The mu-selective opioid antagonist naloxone was considerably more potent than the delta-selective opioid antagonist naltrindole in antagonizing the effects of butorphanol. In each of the training dose groups, the mu opioid agonists morphine, l-methadone and fentanyl, as well as buprenorphine, (-)-pentazocine, nalbuphine, (-)-metazocine and nalorphine, substituted completely for the butorphanol stimulus. The rank order of potency for these compounds in substituting for the butorphanol stimulus was similar across training dose groups and similar to those reported in studies in which fentanyl or morphine were used as training stimuli. (-)-N-allylnormetazocine (NANM) and levallorphan substituted completely for the butorphanol stimulus in the low-dose group, and substituted partially for and antagonized partially the butorphanol stimulus in the medium- and high-dose groups. The kappa opioid agonists spiradoline, bremazocine, U50,488 and U69,593 substituted partially for butorphanol in the low-dose group, an effect that was not reversed by naloxone. In the medium- and high-dose groups, these kappa opioid agonists produced predominantly saline-appropriate responding. The delta opioid agonist BW373U86 substituted completely for butorphanol in the low-dose group, and naltrindole was more potent than naloxone in antagonizing these effects. In the medium- and high-dose groups, BW373U86 substituted partially for the butorphanol stimulus. Unlike the substitution patterns produced by the mu, kappa and delta opioid agonists, the sigma/phencyclidine compounds (+)-cyclazocine and (+)-NANM and the barbiturate pentobarbital produced predominantly saline-appropriate responding in all training dose groups. The present findings suggest that opioids with agonist activity at mu, kappa and delta opioid receptors share similar stimulus effects with a low training dose of butorphanol, whereas only opioids with agonist activity at the mu opioid receptor share stimulus effects with a medium and high training dose of butorphanol.

Analgesics, Opioid↗

Pterygium in lepromatous leprosy.

Pterygia from the eyes of three lepromatous leprosy patients were histopathologically studied. All of the specimens contained acid-fast bacilli (AFB) and exhibited features of chronic inflammation. In the etio-pathogenesis of the pterygium that occurs in leprosy patients, the chronic inflammation that is a feature of the disease, the involvement of the nerves within the pterygium, the increased exposure to sunlight, dust and wind (especially in patients having lagophthalmos), and the ostrasization by society that necessitates living predominantly outdoor lives, should be taken into account.

Aged↗

Targeting antigen into the phagocytic pathway in vivo induces protective tumour immunity.

Cytotoxic T lymphocytes (CTLs) kill neoplastic or virally infected cells after recognizing on their surface antigenic peptides bound to major histocompatibility complex class I molecules. These peptides are derived from antigens that are degraded in the cytosol of the affected cell. Because exogenous proteins cannot enter the cytosol, immunizations with killed pathogens or their proteins do not generally elicit CTLs. However, antigens that are internalized into phagocytic cells can enter the cytosol and be processed for class I presentation. Here we show that immunization with a purified antigen on an avidly phagocytized particle primes CTLs, which in turn protect animals from subsequent challenge with tumours transfected with the antigen gene. Interestingly, these animals also become immune to other antigens expressed by the tumour. This approach could be exploited to develop tumour and viral vaccines.

Amino Acid Sequence↗

Comparative evaluation of a commercial enzyme immunoassay for the detection of human antibody to Rickettsia typhi.

A commercial enzyme immunoassay kit called the Dip-S-Ticks (DS) for the detection of total immunoglobulin (Ig) G and IgM human antibodies to Rickettsia typhi was evaluated. In tests with 340 serum samples from patients with diagnosed cases of rickettsial diseases, patients suffering from other febrile illnesses, and normal subjects, the DS compared favorably with the standard indirect fluorescent-antibody (IFA) test. At IFA cutoff titers of > or = 1.64 and > or = 1:128, the DS showed sensitivities of 88.2 and 91.4% and specificities of 91.8 and 87.7%, respectively. The DS test correlated significantly with both the IFA IgG (r = 0.84, P < 0.0005) and IgM (r = 0.63, P < 0.0005) titers. Only 80% of IgG and 82% of IgM IFA readings determined by two technicians were within one dilution, while the DS was more reliable, with 100% within one dot. The rapidity, reliability, and simplicity of the DS suggest that it is a suitable test for use in clinical laboratories unable to perform the IFA test.

Antibodies, Bacterial↗

Case management in psychiatry: an analysis of tasks.

OBJECTIVE: The authors analyze the concept of case management from the perspective of the task areas of psychiatry and demonstrate the importance of case management in the organization of psychiatric services. METHOD: The relevant literature was reviewed, and a functional analysis of current practices is provided. RESULTS: Case management is an ambiguous concept without a clear base in a professional discipline, and thus there is ongoing uncertainty about its mission, practice, and training, as well as authority and accountability issues. The activities of the case manager in both the private and the public sectors entail work in the task areas of medical care, rehabilitation, social control, growth and development, and social welfare. In all of these areas, the case manager may function in boundary management and in system enhancement and development as well as provide clinical services. CONCLUSIONS: Case management has considerable potential as a means of organizing and delivering mental health services in a cost-effective manner as long as its purpose, practice, and organizational structures are consistent. Psychiatrists should be involved in the organization of case management services.

Health Services Administration↗

Complications of cervical discography: analysis of 4400 diagnostic disc injections.

Despite extensive experience with diagnostic cervical disc injection, the role of this procedure in the evaluation of patients with degenerative disc disease and severe neck pain remains controversial. Beyond the debate regarding its efficacy in identifying the site of cervical symptomatology and directing appropriate intervention are the potential morbidity and mortality associated with this diagnostic procedure. Discitis, subdural empyema, spinal cord injury, vascular injury, and prevertebral abscess have all been reported as complications of diagnostic cervical disc injection. Any meaningful assessment of the role of cervical discography in the evaluation of degenerative disc disease must include a determination of the risks inherent in the procedure. We retrospectively analyzed 4400 cervical disc injections in 1357 patients performed by an experienced radiologist between 1988 and 1993 to define the morbidity and mortality associated with discography. In addition, we reviewed the extant medical literature on the complications of this controversial procedure. This study demonstrates significant complications from diagnostic discography procedures occurring in less than 0.6% of the patients and 0.16% of the cervical disc injections.

Abscess↗

Effects of short-term cortisol infusion on growth hormone-releasing hormone stimulation of growth hormone release in sheep.

Excess production or long-term administration of glucocorticoids is detrimental to longitudinal growth in people and rats. A portion of this effect is attributed to cortisol inhibition of growth hormone (GH). Glucocorticoid effects are usually studied in subjects under long-term treatment with synthetic, more potent glucocorticoids, and, to the authors' knowledge, have not been examined in domestic animals. We sought to examine the effects of cortisol infusion on GH release in sheep. Cortisol infusion into castrated, male Suffolk sheep (1 to 1.5 years old) caused a significant (P < 0.0001) increase in cortisol concentration. Basal GH release was not affected over the 4-hour period of infusion. Growth hormone-releasing hormone administration stimulated GH release in both groups (P < 0.001); however, the control group had a greater response to growth hormone-releasing hormone than did the cortisol infused group (P < 0.0001). These results were duplicated in cultured sheep pituitary cells. Cortisol inhibition of GH release may be mediated via enhanced somatostatin release, owing to a direct inhibition of somatotrope function, or a combination of both mechanisms. Because of effects of stress and disease in increasing cortisol concentration, additional study of the mechanisms for cortisol inhibition of GH release in sheep needs to be performed.

Analysis of Variance↗

Effectiveness of a dot-blot immunoassay of anti-Rickettsia tsutsugamushi antibodies for serologic analysis of scrub typhus.

We compared a commercially available dot-blot immunoassay system with the indirect immunofluorescence assay (IFA) in tests of known negative and known positive sera from scrub typhus cases. Using a panel of 100 sera from patients with various rickettsial and nonrickettsial infections, we observed that the IFA was 99% specific and the dipstick assay was 98% specific. In tests of 91 sera (30 negative and 61 positive for scrub typhus antibodies) from a study of febrile patients in Malaysia, using the standard of an IFA titer < 1:64 as negative, an IFA titer > 1:128 as positive, and an IFA titer = 1:64 as either positive or negative (supported by clinical records), dipsticks were 83% specific and 90% sensitive. The quantitative correlation of the dipsticks to IFA titers was confirmed by significant differences in geometric means of inverse IFA titers corresponding to the number of positive dipstick spots (no dots = 8.5, one dot = 43.3, two dots = 206.7, and three dots = 676.9). The assay would enable physicians and public health workers who deal with patients to quickly diagnose and appropriately treat most cases of the disease, especially in areas of high prevalence where the proportion of false-positive results to true-positive results would be low.

Antibodies, Bacterial↗

Production, purification, and characterization of human matrilysin (PUMP) from recombinant Chinese hamster ovary cells.

A process for semicontinuous production of matrilysin zymogen secreted from recombinant Chinese hamster ovary (CHO) cells was developed. The zymogen was purified to apparent homogeneity by sequential ion-exchange and metal chelation chromatography. These processes were scaled-up to purify gram quantities of the zymogen. The N-terminus of the secreted zymogen from the recombinant cells was the same as the observed sequence of the zymogen from natural sources. Furthermore, activation and autocatalysis of the recombinant zymogen resulted in a form with an N-terminus identical to that of the corresponding native enzyme. The three C-terminal amino acids of both the recombinant zymogen and the corresponding smaller activated form were missing. Activated matrilysin was shown to have activity against a synthetic peptide substrate. The large quantities of matrilysin that can be produced and purified from the recombinant CHO cells will be useful in determination of the structure of matrilysin.

Amino Acid Sequence↗