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Biomedical subjects

J K Wright

Publications and source records attributed to J K Wright.

At least 19 recordsLinked to original sources

Rupture and hemorrhage of hepatic focal nodular hyperplasia.

Although adenoma and focal nodular hyperplasia (FNH) are both benign liver lesions, adenomas are associated with a risk of rupture and malignant degeneration. This had led to the general recommendation of resection of adenomas. However, FNH rarely ruptures or becomes malignant, and a nonoperative approach has been adopted by most hepatobiliary centers when the diagnosis of FNH can be made with reasonable certainty. There are only two previous reports of rupture of FNH in the English literature; we present a third case of FNH with spontaneous rupture and hemorrhage. An 18-year-old healthy Caucasian woman presented with sudden onset of severe RUQ pain. She had never been pregnant, nor used oral contraceptive agents, and had not sustained major trauma. Her abdominal exam revealed RUQ tenderness on palpation. Hepatic biochemical tests, CBC, and coagulation tests were normal. Her hematocrit of 44% fell to 31% over 48 hours. CT scan revealed right anterior lobe and left medial segment hypodense liver lesions (4-5 cm) as well as hemoperitoneum and angiography revealed hypervascular lesions. At laparotomy, two tan fibrous subcapsular masses were excised. Pathology showed a central stellate scar in both lesions with several nodules surrounding the central scar on microscopic section, characteristic of FNH. There was evidence of hemorrhage in one lesion. Significant symptoms are an indication for resection of FNH lesions. However, most patients with FNH are asymptomatic and have a normal physical exam. The natural history of these lesions is enigmatic, and the indications for surgery are still evolving. This report emphasizes that a small risk of rupture clearly exists.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma, Liver Cell

The differential responses of human skin and synovial fibroblasts to stanozolol in vitro: production of prostaglandin E2 and matrix metalloproteinases.

The anabolic steroid, stanozolol, is used therapeutically to treat a number of pathological conditions and its clinical effects suggest that it can modulate connective tissue breakdown. The ability of this compound to stimulate prostaglandin E2 (PGE2), collagenase, gelatinase and stromelysin production by human synovial and skin fibroblasts in vitro was examined. The results showed that stanozolol significantly stimulated, in a dose dependent manner, PGE2, collagenase and stromelysin production by skin fibroblasts. However, no stimulation was seen in the synovial cell lines. In contrast, no effect on gelatinase production was seen in either cell type, following exposure to stanozolol. The synovial and skin lines both exhibited a significant stimulation of PGE2 and all three metalloproteinases in response to interleukin-1 beta (IL-1 beta). The anabolic steroids nortestosterone and oxymetholone demonstrated no ability to stimulate PGE2 or collagenase production in either skin or synovial fibroblasts. These results suggest that stanozolol exerts differential effects on skin and synovial fibroblasts in vitro which may enable the elucidation of the mechanism of action of the compound in vivo.

Cell Survival

Polyclonal antibodies against human fibroblast collagenase and the design of an enzyme-linked immunosorbent assay to measure TIMP-collagenase complex.

A polyclonal antibody has been raised against purified human fibroblast collagenase and characterised. This antibody has been used in combination with a monoclonal anti-TIMP antibody in a double antibody sandwich ELISA to measure TIMP-collagenase complex. The assay range was 5-50 ng/ml complex, quantitated in terms of the TIMP component. The assay can measure complex even in the presence of at least a 40-fold excess of free TIMP. The level of TIMP-collagenase complex has been measured in serial samples of synovial fluid from two patients with septic arthritis; high levels of complex are found in some samples, and the level of complex shows an inverse relationship with the level of free TIMP.

Adult

Monoclonal antibodies against human fibroblast collagenase and the design of an enzyme-linked immunosorbent assay to measure total collagenase.

Monoclonal antibodies have been raised against purified human fibroblast collagenase and characterised. One of these antibodies has been used in combination with a polyclonal anticollagenase antibody in a double antibody sandwich ELISA to measure collagenase. The assay range was 2-50 ng/ml collagenase. The assay measures total collagenase, i.e. pro- and active enzyme as well as collagenase in complex with TIMP. The level of collagenase has been measured in sera samples from patients with rheumatoid arthritis and compared with age- and sex-matched controls. The levels measured were: rheumatoid arthritis, 69 +/- 29 ng/ml; normal, 49 +/- 14 ng/ml.

Antibodies, Monoclonal

The secretion of the tissue inhibitor of metalloproteinases (TIMP) by human synovial fibroblasts is modulated by all-trans-retinoic acid.

The matrix metalloproteinases are a family of enzymes involved in the turnover of the connective tissues. The regulation of these enzymes is complex, involving the control of synthesis, the activation of proenzyme forms and the presence of specific inhibitors. Retinoids have been reported to inhibit the production of metalloproteinases by human and rabbit synovial fibroblasts and by human skin fibroblasts. The production of the highly specific tissue inhibitor of metalloproteinases (TIMP) by connective tissue cells may be crucial in the regulation of connective tissue breakdown and this present study was undertaken to determine if retinoic acid (RA) could modulate TIMP and collagenase production by synovial fibroblasts. The results show that RA at concentrations from 10(-7) to 10(-5) M significantly stimulated the secretion of TIMP by two of three human synovial cell lines. The effect of mononuclear cell factor (MCF) on TIMP and collagenase levels was also investigated. The apparent reduction of collagenase levels in the presence of RA, could result from a failure to accurately measure this enzyme in the presence of increased levels of TIMP.

Arthritis, Rheumatoid

Transforming growth factor beta stimulates the production of the tissue inhibitor of metalloproteinases (TIMP) by human synovial and skin fibroblasts.

IL-1 stimulates the secretion of metalloproteinases by a variety of connective tissue cells and is thought to be the primary inducing agent of connective tissue breakdown in rheumatoid arthritis. Transforming growth factor-beta (TGF-beta) is known to be capable of inhibiting the synthesis of metalloproteinases and to be able to partially inhibit interleukin-1 (IL-1) induced cartilage degradation. The present paper examines the ability of TGF-beta to modulate the action of IL-1 on fibroblasts of synovial and skin origin and investigates the secretion of the tissue inhibitor of metalloproteinases (TIMP) by these cells after exposure to TGF-beta and IL-1. The principal findings are that when four out of five fibroblast lines were exposed to TGF-beta and IL-1 in combination they displayed a significant increase in TIMP secretion; furthermore, in two of these cell lines a significant stimulation of TIMP secretion was induced by TGF-beta alone.

Adult

Polyclonal and monoclonal antibodies against human tissue inhibitor of metalloproteinases (TIMP) and the design of an enzyme-linked immunosorbent assay to measure TIMP.

Both polyclonal and monoclonal antibodies have been raised against purified human fibroblast tissue inhibitor of metalloproteinases (TIMP) and characterised. Combinations of antibodies were tested for their suitability in a double antibody sandwich ELISA to measure TIMP. Two combinations were applicable to the immunoassay: (i) a monoclonal capture antibody with a polyclonal detecting antibody; (ii) two monoclonal antibodies. The assay range was (i) 2-50 ng/ml and (ii) 5-50 ng/ml of human TIMP. The levels of TIMP in several human body fluids were measured using assay (ii), and values in ng/ml with standard deviations (n-1) obtained as follows: serum, 299 +/- 62; plasma, 109 +/- 35; amniotic fluid, 724 +/- 62; cerebrospinal fluid, 144 +/- 156; saliva, 209 +/- 103.

Animals

Rheumatoid factor quantitation: a comparison of ELISA and nephelometric methods.

Quantitation of rheumatoid factors (RF) by nephelometry, and more recently by enzyme linked immunosorbent assay (ELISA), are achieving increasingly common usage. Sera from 101 rheumatoid patients were compared by both methods and screened by a latex fixation method. Good correlation was found between the two assay techniques, the ELISA showing greater sensitivity and measuring IgG RF and IgA RF in addition to IgM RF. Both assay methods were reliable, accurate, rapid and sensitive for routine clinical purposes.

Enzyme-Linked Immunosorbent Assay

Prolonged survival of nonhuman primate renal allograft recipients treated only with anti-CD4 monoclonal antibody.

The immunosuppressive efficacy of the monoclonal antibody OKT4A reactive with human and monkey CD4 cells was evaluated in cynomolgus renal allograft recipients. Low-dose (0.1 to 0.3 mg/kg/day) intact monoclonal antibodies (10 recipients) or F(ab')2 fragments (two recipients) were administered for 12 days. High-dose OKT4A (10 mg/kg) was administered on the day of transplantation as the only suppression in five animals. Four control animals received either no therapy or a monoclonal antibody nonreactive with monkey cells (OKT3). Maximum survival of the control animals and those treated with F(ab')2 was 11 days. Mean survival in the recipients of low-dose OKT4A was 25.4 +/- 4.3 days and in the group receiving high-dose OKT4A it was 39 +/- 6.4 days. All OKT4A-treated animals showed "coating" and CD4 modulation without depletion of circulating T cells. No modulation occurred in the F(ab')2-treated recipients. Serial allograft biopsy specimens showed reduced lymphocyte infiltration that was nearly complete in recipients of high-dose OKT4A. Biopsy-derived donor-reactive cytotoxic T-cell lines were generated regularly from recipients of low-dose, but not high-dose, OKT4A during periods of stable function. All animals treated with monoclonal antibodies developed an immunoglobulin G antimurine humoral response. Thus OKT4A is a potent immunosuppressive agent administered even as a single bolus, and depletion of CD4 cells is not required to suppress rejection. Anti-CD4 monoclonal antibodies may prove useful in patients, perhaps requiring only a limited number of higher-dose injections in the peritransplant period.

Animals

The effect of the anabolic steroid, stanozolol, on the production of procollagenase by human synovial and skin fibroblasts in vitro.

The ability of the anabolic steroid, stanozolol, to stimulate procollagenase production by human synovial and skin fibroblasts was examined in an in vitro assay system. Stanozolol is used therapeutically to treat a variety of connective tissue and vascular disorders and its clinical effects suggest that it can modulate connective tissue breakdown. The results showed that stanozolol was capable, in a dose dependent manner, of significantly stimulating procollagenase production by skin fibroblasts. However, in three synovial fibroblast lines no evidence was found of increased collagenase production following treatment with stanozolol; although the synovial fibroblasts secreted significantly increased amounts of procollagenase in response to IL-1. These results may shed some light on the mechanism of action in vivo of stanozolol in the treatment of connective tissue disorders.

Cells, Cultured

Scrotal reconstruction with a rectus abdominis muscle flap.

The rectus abdominis muscle flap provides excellent coverage of major scrotal defects. It is a simple, reliable, one-stage procedure which covers the exposed testes and gives a satisfactory aesthetic result and is an ideal choice for covering the contaminated wound.

Abdominal Muscles

Patent blue V encapsulation in liposomes: potential applicability to endolympatic therapy and preoperative chromolymphography.

The water soluble dark blue stain Patent Blue V was incorporated into liposomes to increase its depot properties. Experiments with intraperitoneal and intramuscular application in rats and with intralymphatic injections in rabbits showed a substantial difference between the pharmacokinetics of aqueous and liposomal solutions. Independent of the route of administration, the dye-stain remained much longer in the tissues using liposomes. Most notably, retroperitoneal lymph nodes in rabbits remained dark blue up to 28 days after hindlimb endolymphatic instillation of liposomal patent blue. This vastly superior depot effect may be clinically adaptable for endolymphatic therapy with cytostatic drugs to enhance nodal drug retention and concentration or for preoperative chromolymphography to facilitate nodal visualization at laparotomy.

Animals

Lactose permease of Escherichia coli: properties of mutants defective in substrate translocation.

Mutants of lactose permease of Escherichia coli with amino acid changes (Gly-24----Glu; Gly-24----Arg; Pro-28---Ser; Gly-24, Pro-28----Glu-Ser and Gly-24, Pro-28----Arg-Ser) within a putative membrane-spanning alpha-helix (Phe-Gly-Leu-Phe-Phe-Phe-Phe-Tyr-Phe-Phe-Ile-Met-Gly- Ala-Tyr-Phe-Pro-Phe-Phe-Pro-Ile) are incorporated into the cytoplasmic membrane. The mutant proteins retain the ability to bind galactosides, and the affinity for several substrates is actually increased. However, the rate of active transport is decreased to 0.01% of the wild-type rate in the mutants carrying Arg-24 or Arg-24, Ser-28. Kinetic analysis demonstrates that the two mutants require 10 min to cause occupied binding sites for galactoside and H+ to change their exposure from the periplasm to the cytoplasm as compared to 50 ms in the wild type. The effect is less pronounced when these sites are unoccupied.

Amino Acid Sequence

Isolation and growth characteristics of adult human tendon fibroblasts.

An explant method for the isolation of fibroblasts from adult human tendon is described. Cells were successfully isolated from 22 out of 27 common biceps tendons obtained from cadaveric donors (age range 11-83 years). The fibroblasts could be maintained in culture using standard methods and morphologically resembled those of synovial rather than dermal origin. Growth characteristics of 12 cell lines were assessed by deoxyribose nucleic acid (DNA) synthesis using [3H]thymidine incorporation in response to stimulation by fetal calf serum. Cells obtained separately from superficial and deep parts of the tendons produced almost identical responses. No significant reduction in growth response with increasing age was found when related to the age of the donor. Therefore this study did not show any age related defect in the short term tendon fibroblast replicative responses to serum.

Adolescent