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Biomedical subjects

R Rees

Publications and source records attributed to R Rees.

At least 19 recordsLinked to original sources

C-myc oncogene expression in ocular melanomas.

We have investigated the expression of c-myc in 24 ocular melanomas by immunohistochemistry, using two monoclonal antibodies raised against a mid-sequence portion of the c-myc product (6E10) and against the C-terminus (9E10). The results were compared with other putative prognostic factors, including tumour size, cell type, proliferation index (determined by flow cytometry), and ploidy, as well as immunohistochemical staining for HMB-45 and S-100 antigens. Staining, often focal, for c-myc was found in both the nucleus and the cytoplasm of a proportion of the cells in most tumours studied. Total cell staining for myc protein correlated with proliferative index in diploid tumours; seven out of nine aneuploid and mixed aneuploid/diploid cells showed strong staining in at least one cellular compartment. A positive correlation with myc expression was also found for HMB-45 staining, but not for cell type or staining for S-100. The results support the hypothesis that myc protein is involved in cellular proliferation in uveal melanomas and indicate that immunohistochemistry for myc antigen may be a useful prognostic marker in these tumours.

Adult

Relationship between neuropeptide immunoreactive nerves and inflammatory cells in adjuvant arthritic rats.

The purpose of this study was to assess the relationship of neuropeptide nerves and inflammatory leukocytes in PVG rats with adjuvant-induced arthritis. Substance P- and calcitonin gene-related peptide (CGRP)-immunoreactive nerves and inflammatory leukocytes were studied, using peroxidase (ABC) and/or alkaline phosphatase (APAAP) staining. Inflamed synovial tissue proper was infiltrated with neutrophils, ED1 macrophages and focal accumulations of CD2 T lymphocytes. In such tissue, the relationship between peptide-immunoreactive nerves and inflammatory cells was such that substance P and CGRP nerves were absent in heavily infiltrated villous synovial tissue, whereas healthy synovial tissue and non-inflammatory areas in adjuvant arthritic rats were innervated by substance P and CGRP nerves close to normal synovial tissue resident cells. In order to elucidate an eventual mechanism for lost immunoreactivity, healthy synovial tissue was exposed to chymotrypsin or oxygen derived free radicals (ODFR) in vitro. The former treatment caused total loss of immunoreactivity. These findings suggest that neuropeptides and neuropeptide containing nerves may be destroyed by locally produced proteolytic enzymes and various reactive oxygen species in the vicinity of inflammatory cells.

Animals

Evidence that interleukin-4 suppression of lymphokine-activated killer cell induction is mediated through monocytes.

Recombinant human interleukin-4 (IL-4) and transforming growth factor-beta (TGF-beta) reduce recombinant interleukin-2 (IL-2) induction of lymphokine-activated killer (LAK) cell activity from human peripheral blood mononuclear cells (PBMC). Monocytes can be removed from PBMC by adherence, leaving a peripheral blood lymphocyte population (PBL) which also responds to IL-2 to generate LAK activity. PBL generation of LAK cytotoxicity is susceptible to inhibition by TGF-beta, but not by IL-4. Readdition of purified monocytes to PBL is accompanied by return of the suppressive action of IL-4 on the generation of LAK activity. Induction of LAK cytolysis from Percoll-isolated T cells (greater than 90% CD3+) is also refractory to the inhibitory effect of IL-4. When PBMC were cultured in IL-2, with and without IL-4, subsequent sorting of CD3+ and CD3- lymphocytes by flow cytometry demonstrated that IL-4 had suppressed LAK induction in both effector populations. This suggests that, although isolated CD3+ cells are not susceptible to IL-4 suppression of IL-2 activation, they are sensitive to inhibition when part of a mixed PBMC population. Evidence is presented for the first time that this suppression is mediated via the action of IL-4 on monocytes.

Cell Adhesion

Xanthine oxidase: its role in the no-reflow phenomenon.

This study was designed to probe the hypothesis that oxygen-derived free radicals are involved in initiation of the no-reflow phenomenon. We developed a reproducible model of no reflow in the rat hind limb. Laser Doppler studies confirmed that the hind limbs perfused well after 2 or 4 hours of ischemia, but perfusion ceased in the first 10 minutes after 6 hours of ischemia. Venous blood samples and biopsy specimens of skin and muscle were taken after 2 and 4 hours of ischemia to study tissue injury. Blood samples were evaluated for xanthine oxidase (XO), xanthine dehydrogenase, and creatine phosphokinase (CPK) activities. Conjugated dienes and iodine 125-labeled albumin extravasation were quantified in tissue samples. Groups of animals were treated with inhibitors of XO (allopurinol), antioxidant enzymes (superoxide dismutase plus catalase), and free radical scavengers (dimethyl sulfoxide and dimethyl thiourea) to assess the roles of free radicals in ischemia-reperfusion injury in the hind limbs. After 4 hours of ischemia followed by reperfusion, plasma XO activity rose threefold over preischemia levels (p less than 0.05). Xanthine dehydrogenase activity did not change; conjugated diene levels in muscle rose twofold; CPK levels rose sixfold, and 125I albumin extravasation rose twofold (p less than 0.05). Pretreatment with the XO inhibitor allopurinol reduced XO activity to negligible levels and significantly attenuated conjugated diene levels, CPK levels, and albumin extravasation. Albumin extravasation was also significantly attenuated by pretreating animals with superoxide dismutase together with catalase, dimethyl thiourea, and dimethyl sulfoxide. In all animals pretreated with allopurinol or superoxide dismutase and catalase, reperfusion persisted after 6 hours of ischemia. These data suggest that, in ischemia followed by reperfusion, tissue injury is related to oxygen products derived from XO activity.

Allopurinol

Tooth inversion.

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Humans

Acute lung injury following reperfusion after ischemia in the hind limbs of rats.

In this study, we proposed that oxygen free radicals participate in the acute pulmonary injury that follows limb ischemia/reperfusion. Using an established model of hind limb ischemia, reproducible lung injury occurred after reperfusion. Lung microvascular permeability was measured with 125I-BSA and increased two-fold after 30 minutes of reperfusion. Pulmonary injury was blocked with DMSO, DMTU, allopurinol, indomethacin, and SOD plus catalase. The degree of pulmonary neutrophil sequestration as assessed by tissue myeloperoxidase activity was significantly diminished in animals pretreated with antioxidants. Pretreatment with indomethacin did not attenuate the neutrophil sequestration within the pulmonary parenchyma. These data suggest that increased lung microvascular permeability and neutrophil accumulation occur following hind limb ischemia/reperfusion. Therapeutic interventions with oxygen radical inhibitors blocked this process, while the prostaglandin inhibitor, indomethacin, only reduced lung permeability.

Allopurinol

Regional distribution of mast cells and peptide containing nerves in normal and adjuvant arthritic rat synovium.

Simultaneous visualization of nerves and mast cells in the rat synovium was possible with double staining. Thus, a direct comparison could be made of nerves and mast cells in the ankle joints of healthy rats and in those with severe adjuvant induced polyarthritis. Nerves were studied with avidin-biotin-peroxidase complex (ABC) immunostaining, using heterologous antisera to protein gene product 9.5 (PGP 9.5), a recently discovered neural protein, and the neuropeptides substance P and calcitonin gene related peptide (CGRP). Mast cells were visualized by metachromatic staining of granule heparin. With double staining of sections, a parallel distribution of mast cells and nerves in all parts of the normal synovium was noted. In rats with adjuvant induced arthritis, a near total parallel disappearance of mast cells and nerves in the synovium occurred. In the arthritic rat such mast cell/nerve "units" were only present in the region where synovium attaches to bone. The observed regional depletion of both nerves and mast cells in arthritis may be of importance in the pathophysiology of arthritis.

Animals

Nerves in inflammatory synovium: immunohistochemical observations on the adjuvant arthritis rat model.

Previous evidence has been presented that neurogenic input may influence adjuvant induced arthritis (AA) in rats. We now present evidence of alterations in synovial nerves in AA. Nerves were studied in well perfused and fixed rats, using immunohistochemistry with the sensitive avidin-biotin peroxidase complex (ABC) method and heterologous antisera to cytoskeletal protein gene product 9.5 (PGP) and the neuropeptides substance P and calcitonin gene related peptide (CGRP). The innervation of synovium was compared in normal rats and rats with AA. Observations concordant with what has been reported for neuropeptide nerves in the synovium of patients with rheumatoid arthritis (RA) are presented. It has been suggested that neural peptide substances are reduced in nerves of synovium from patients with RA. In the AA rat a specific reduction of lining zone and sublining nerves in the synovium was noted. The AA rat model is very suitable for studying the involvement of synovial nerves in arthritis, permitting optimal preservation of immunoreactive neural epitopes.

Animals

Massive schwannoma of the nose and paranasal sinuses.

Schwannomas, uncommon tumors of the nose and paranasal sinuses, are discovered late in their clinical course because of their obscure anatomic location. In this report, we have described the clinical findings in a massive nasal schwannoma (neurilemoma) that obstructed both nares, the left maxillary sinus, and the ethmoid sinuses, and protruded from the oropharynx and nose. The preoperative work-up included both computerized tomographic and magnetic resonance imaging studies.

Diagnosis, Differential

Pharyngocutaneous fistulas in advanced cancer: closure with musculocutaneous or muscle flaps.

Two hundred cases of head and neck cancer were reviewed and 16 pharyngocutaneous fistulas identified, for an incidence of 6 percent. The fistulas were closed with pectoralis major muscle flaps in four patients, pectoralis musculocutaneous flaps in seven patients, sternocleidomastoid muscle flaps in four patients, and latissimus dorsi flaps in two patients. Four types of fistulas were identified, and flap selection was determined by fistula location. Successful closure was obtained in 15 patients (88 percent), although one patient died from recurrence with a persistent fistula.

Combined Modality Therapy

Pleomorphic adenoma of the cervical esophagus: a rare tumor.

Pleomorphic adenoma of the esophagus is a rare tumor: less than 10 cases have been reported. These pleomorphic neoplasms are sessile and arise in the submucosal glands of the esophagus. Described in this report is the long-term follow-up of an additional case, in which the resection was reinforced with a pectoralis major muscle wrap.

Adenoma

The diagnosis and treatment of brown recluse spider bites.

We reviewed our experience with 95 patients who carried the diagnosis of brown recluse spider bite between 1983 and 1986 and identified a reference group of 17 with confirmed bites. Eight men and seven women, average age 32 years, presented within 33 hours following the bites. The most common symptoms were pain, pruritus, malaise, chills, sweats, and rash. Patients were randomized into three treatment groups: dapsone, brown recluse spider antivenom, or combination therapy. All patients were treated with erythromycin. If two patients with very severe lesions were excluded, patients in all groups healed their wounds in an average of 20 days. A comparison of our treatment was attempted with all other bites previously confirmed in the literature, but historical data were incomplete and no conclusions could be drawn.

Adult

A comparative study of the anti-proliferative effects of calmodulin antagonists in cultured cells--W7 derivatives of improved cytostatic potential.

We have compared the effects of the calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalene-sulphonamide (W7) and relatives of the parent compound, modified by substituting the 5-chloro- for an iodo-residue and increasing stepwise the length of the carbon chain from 6 to 12, for their ability to inhibit cell proliferation in tissue culture. These species showed improved specificity and potency, as determined against a calcium calmodulin-dependent beef heart phosphodiesterase in vitro, exhibited time courses of inhibition similar to the parent compound W7, but were more potent at inhibiting DNA synthesis in K562 human leukaemic cells cultured in serum-free medium. The elevation observed in the percentage of cells in G1 of the cell cycle following drug exposure indicated that these drugs, like W7, arrested growth by inhibiting entry of cells into and through S phase. Higher doses of all drugs were irreversibly cytotoxic as determined by the inability of the cells to recover DNA synthetic capacity and to form colonies in soft agar or to recover their normal cell cycle distribution. We also discuss the possible implications of extracellular calmodulin and antagonism thereof on cell proliferation.

Animals

Latissimus dorsi flap: a valuable resource in lower arm reconstruction.

Lower arm reconstruction of soft tissue defects and after ablation for cancer leaves the reconstructive surgeon few alternatives. We have used latissimus dorsi muscle (n = 1) and musculocutaneous flaps (n = 3) with good functional and cosmetic results. Defects in one patient with traumatic amputation, another with extravasation of doxorubicin, and two with cancer were closed without complications to donor site, recipient site, or flap. Skin paddle size averaged 182 sq cm in the three musculocutaneous flaps. Mean follow-up was six months.

Aged

Comparative modes of action of lactitol and lactulose in the treatment of hepatic encephalopathy.

Lactitol, an unabsorbed sugar with defined laxative threshold and superior taste properties has been suggested as an alternative to lactulose in the treatment of hepatic encephalopathy. In the present study we have compared the colonic metabolism of the two sugars using an in vitro faecal incubation system. Both sugars were readily metabolised by faecal bacteria producing volatile fatty acids and the metabolism was inhibited by neomycin. The effect of lactitol and lactulose on terminal ileal and colonic pH was monitored in six normal subjects using a radiotelemetry technique. Both sugars significantly lowered right colonic pH (basal -6.51 +/- 0.48 vs lactitol -5.63 +/- 0.50; lactulose -5.18 +/- 0.82, p less than 0.05). The pH of rest of the colon and terminal ileum was unaffected. Neomycin given concurrently with lactulose abolished acidification of right colon. As lactitol and lactulose have similar effects within the colon, lactitol would appear to have a role in the treatment of hepatic encephalopathy. As neomycin antagonises the effect of lactulose in the colon, its concurrent use may be less effective in the treatment of hepatic encephalopathy.

Colon

Carney's triad: gastric leiomyosarcoma, pulmonary chondroma and extra-adrenal paraganglioma in young females.

The case of a 13-year-old girl with a gastric leiomyosarcoma and a pulmonary osteochondroma is presented. The association of these two tumours and extra-adrenal paraganglioma has been described as a triad by Carney. The patient is free of recurrence of the gastric tumour with no evidence of paraganglioma 10 months after the operation. To our knowledge this is the first case of the triad reported in the UK.

Adolescent