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Biomedical subjects

W G Jones

Publications and source records attributed to W G Jones.

At least 19 recordsLinked to original sources
PubMed1992

Macrophage inflammatory protein 1 modulates macrophage function.

Macrophage inflammatory protein 1 (MIP 1), initially purified from the conditioned medium of endotoxin-stimulated macrophages, is a low m.w. heparin-binding protein doublet comprising two peptides, MIP 1 alpha and MIP 1 beta. Although native doublet MIP 1 has previously been shown to exert pyrogenic, mitogenic, and proinflammatory effects on other cell types, its actions on its cell of origin, the macrophage, have not been well catalogued. Our study reports several aspects of macrophage function that are modulated by MIP 1. MIP 1 was not directly cytotoxic for WEHI tumor cells, but MIP 1-treated macrophage exhibited enhanced antibody-independent macrophage cytotoxicity for tumor targets. MIP 1 treatment stimulated proliferation of mature tissue macrophages, and this effect was enhanced upon costimulations with either CSF-1 or granulocyte-macrophage-CSF. Thioglycollate-elicited peritoneal exudate macrophages incubated with native doublet MIP 1-secreted bioactive TNF and IL-6, as well as immunoreactive IL-1 alpha, and these effects were enhanced significantly when the cells were costimulated with IFN-gamma. Purified preparations of the recombinantly derived MIP 1 alpha peptide alone stimulated the secretion of TNF, IL-1 alpha, and IL-6 by peritoneal macrophages, but MIP 1 beta did not. In fact, as little as eightfold excess MIP 1 beta blocked TNF-induction by MIP 1 alpha to a significant degree. By contrast to these apparent "macrophage activating" properties of MIP 1, the cytokine failed to trigger the macrophage oxidative burst, or to up-regulate the expression of Ia on the macrophage surface. Taken together, these data reveal that MIP 1 peptides act as autocrine modulators of their cells of origin, and raise the possibility that MIP 1 peptides may play a role in modulating macrophage responses to inflammatory stimuli in vivo.

Animals↗
PubMed1992

Esophageal perforation: a continuing challenge.

Perforation of the esophagus remains a diagnostic and therapeutic challenge. Currently, the most common cause of perforation is instrumentation of the esophagus, and the incidence of esophageal perforations has increased as the use of endoscopic procedures has become more frequent. Diagnosis depends on a high degree of suspicion and recognition of clinical features, and is confirmed by contrast esophagography or endoscopy. Outcome after esophageal perforation is dependent on the cause and location of the injury, the presence of underlying esophageal disease, and the interval between injury and initiation of treatment. Reinforced primary repair of the perforation is the most frequently employed and preferable approach to the surgical management of esophageal perforations. Nonoperative management consisting of antibiotics and parenteral nutrition is particularly successful for limited esophageal injuries meeting proper selection criteria.

Esophageal Perforation↗
PubMed1992

Effect of cyclosporine on adrenocortical response to injury and infection.

The effects of cyclosporine administration on the adrenocortical response to the severe stress of burn wound sepsis were studied in Wistar rats. Animals were treated with cyclosporine (10 mg/kg/day) or saline by gavage for 10 days, then subjected to 30% scald burns with wound inoculation with Pseudomonas. Animals were sacrificed on Postburn Days (PBDs) 1, 4, and 7 for determination of serum corticosterone and ACTH levels and adrenal weights and histology. Adrenal glands from animals sacrificed on PBD 7 were also analyzed for DNA, RNA, and protein content. Cyclosporine treatment without injury had no significant effect on body weight gain, adrenal mass, or baseline ACTH or corticosterone levels. During sepsis, cyclosporine-treated animals demonstrated a significantly diminished adrenocortical response compared to those given only saline. Serum corticosterone levels in the cyclosporine group were 45, 53, and 62% lower on PBDs 1, 4, and 7, respectively, than in saline-treated controls (P < 0.01 on each day). ACTH levels were 43 and 36% lower in cyclosporine-treated animals on PBDs 4 and 7, respectively, compared to the saline-treated group (P < 0.05 on each day). Adrenal hyperplasia occurred in both groups by PBD 7, but increases in adrenal mass and in histologic changes associated with hyperplasia (lipid depletion, vascular dilation) were less pronounced in cyclosporine-treated animals compared to those receiving saline, while adrenal composition remained similar between the two groups. Thus, cyclosporine administration is associated with an attenuated adrenocortical response to the stress of sepsis due to diminished circulating levels of ACTH.

Adrenal Cortex↗
PubMed1992

Effect of sepsis on intracellular sodium activity, sodium concentration, and water content in thermal injured rat.

The effects of sepsis on intracellular Na+ activity, Na+ concentration, and H2O partition in skeletal muscle were investigated in a burn rat model. Studies were performed on either postburn day 3 or day 7 during evolving burn wound sepsis. Data are compared among 3 groups of rats: burned and infected (BI), burned not infected (B), and sham burn (C). After 3 days postburn both Na+ activity and concentration decreased in the BI group as compared with B and C groups. By postburn day 7, the BI group developed septic shock and had increased intracellular Na+ activity and concentration. The resting membrane potentials of skeletal muscle cells depolarized. The finding of an increased cell membrane relative permeability of Na+ to K+ could account for the increase in Na+ influx into cells. In addition, intracellular and total muscle H2O contents decreased and extracellular H2O increased. Hypernatremia, hyperchloremia, and hyperosmolality were also observed in the BI group. However, the fact that there was no significant difference between B and C groups indicates that the late derangements were due to septic shock rather than simple burn injury. Thus, the deleterious effects of the evolving burn wound sepsis on Na+ homeostasis might be due to the detrimental effect of increased intracellular Na+ activity on mitochondrial respiratory control with subsequent impairment of cellular functions.

Animals↗
PubMed1991

Pathophysiologic glucocorticoid levels and survival of translocating bacteria.

Burn wound sepsis in rats results in sustained corticosterone elevations and the prolonged presence of translocated bacteria in the mesenteric lymph nodes (MLNs). To determine if survival of bacteria in the MLNs may be influenced by pathophysiologic corticosterone levels, MLNs were quantitatively analyzed from rats randomized to the following groups: burn wound sepsis (BI); BI with adrenocortical response attenuated by cyclosporine (cyclosporine/BI); or cyclosporine/BI with corticosterone replacement (cyclosporine/BI + P). Although rates of bacterial translocation were similar, corticosterone levels were significantly different among the three groups and correlated with the number of lymphocytes and the number of enteric bacteria present per gram of MLN. Thus, pathophysiologic elevations of corticosterone levels during sepsis may exert an effect that allows survival of translocated bacteria in the MLNs of rats, perhaps due to glucocorticoid-associated alterations in regional immunity.

Administration, Cutaneous↗
PubMed1991

Bacterial overgrowth and intestinal atrophy in the etiology of gut barrier failure in the rat.

Bacterial translocation occurs in animal models of shock, trauma, sepsis, and parenteral or elemental enteral alimentation. Bowel atrophy and cecal bacterial overgrowth have both been implicated in the pathophysiology of bacterial translocation in many of these models. To further define the etiology of bacterial translocation resulting from dietary manipulations, rats were fed a elemental/defined-formula diet (DFD) for 2 weeks ad libitum and then randomized to either intestinal decontamination with a nonabsorbable antibiotic (neomycin) or no antibiotic treatment. Neomycin treatment significantly (p less than 0.01) reduced the incidence of bacterial translocation after DFD, in association with a significant reduction in the number of cecal gram-negative bacteria. Neither loss of bowel mass after DFD nor bowel composition was affected by oral neomycin. Bacterial translocation after DFD would thus appear to be the result of cecal bacterial overgrowth rather than a loss of a physical intestinal barrier due to atrophy.

Animals↗
PubMed1991

Diabetes impairs the late inflammatory response to wound healing.

Diabetes mellitus is recognized as a risk factor for compromised wound healing. This study examines leukocyte infiltration and the appearance of tumor necrosis factor-alpha (TNF) and IL-6 in wound chambers implanted in normal and streptozotocin-induced diabetic mice. Perforated silicone wound chambers containing a strip of polyvinyl alcohol sponge were implanted along the flanks of normal and diabetic mice. Wound fluid aspirated from the chambers 1, 3, and 7 days following implantation was analyzed for the total number of leukocytes and TNF and IL-6 levels. While the number of leukocytes in the wound fluid was similar on Days 1 and 3 following implantation, there were significantly fewer inflammatory cells in wound fluid from diabetic animals (13.8 X 10(6)/ml) than in wound fluid from normal animals (28.5 Z 10(6)/ml) on Day 7 following implantation. TNF levels in the cell-free exudate fluid were similar between the two groups on all days examined. IL-6 levels were similar on Days 1 and 3 following implantation between the two groups, but there was significantly more IL-6 in wound fluid from normal animals (10,998 U/ml) than in wound fluid from diabetic animals (2096 U/ml) on Day 7 following implantation. Histologic evaluation of chambers 8 days following implantation revealed decreased neovascularization and less organization of granulation tissue. These data suggest that delayed healing in diabetes is associated with altered leukocyte infiltration and wound fluid IL-6 levels during the late inflammatory phase of wound healing.

Animals↗
PubMed1991

Long-term follow-up of non-seminomatous testicular cancer patients with mature teratoma or carcinoma at postchemotherapy surgery. EORTC Genitourinary Tract Cancer Cooperative Group (EORTC GU Group)

From 1979 to 1983 the EORTC GU Group treated 239 patients with disseminated non-seminomatous testicular cancer with combination chemotherapy comprising cisplatin, vinblastine and bleomycin in a prospectively controlled trial. The protocol required complete resection of residual masses after induction chemotherapy, provided that serum tumour markers were normal. 102 patients were operated on. 27 patients had mature teratoma (teratoma differentiated) in the resected specimens and 23 had viable cancer. Follow-up data were available for 26 and 22 of these patients, respectively. 23 of 26 patients (88%) with mature teratoma are alive and disease free after a follow-up of 53-110 months (median 92 months). 3 patients developed progressive disease; 1 died. A peculiar case of growing mature teratoma on the forearm is described. 13 of 22 patients (59%) with residual carcinoma are alive and disease free after a follow-up of 74-112 months (median 95 months). The prognosis of patients with carcinoma is shown to be correlated with the completeness of surgery, which in turn is correlated with the initial tumour mass before chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

BOP/VIP--a new platinum-intensive chemotherapy regimen for poor prognosis germ cell tumours.

Ninety-one patients with poor prognosis non-seminomatous germ cell tumours (NSGCT) were treated with an initial intensive chemotherapy schedule. Suitable patients fulfilled one or more of the following criteria: lymph node metastases greater than 10 cm diameter; liver, brain or bone metastases; serum HCG level greater than 50,000 IU/L; and extragonadal primary tumours. Treatment consisted of 3 cycles of bleomycin, vincristine and cisplatin (BOP) administered at 10 day intervals, followed by 3 cycles of etoposide, ifosfamide and cisplatin (VIP) at 21 day intervals. A total of 64 patients (70%) achieved a complete remission. This comprised 46 patients who received BOP/VIP only, and 18 patients who received additional chemotherapy after BOP/VIP. Of these 64 patients, 51 underwent complete surgical resection of residual masses, including 11 in whom there was evidence of teratoma with cellular atypia or non-germ cell cancer in the resected tissue. A further 9 patients had persisting unresected radiological masses in the presence of marker complete remission. The overall response rate was 80%. Currently 57 patients (63%) remain alive and free from disease progression. The median follow-up period is 90 weeks (range 24-206 weeks), with a 2 yr actuarial progression-free survival of 66% (95% c.i. 55-77%). Major toxicity was myelosuppression, occurring during the VIP arm of therapy, with a median nadir WBC of 1.1 x 10(9)/L and median platelet count of 51 x 10(9)/L. Other toxicity included peripheral neuropathy (WHO Grade 2 and 3 in 22%). We conclude that treatment results with the BOP/VIP schedule in this poor prognosis patient group are at least comparable with other schedules, and toxicity is manageable.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Differential pathophysiology of bacterial translocation after thermal injury and sepsis.

Bacterial translocation (BT) occurs transiently after thermal injury and may result from an ischemic intestinal insult. To evaluate continued intestinal ischemia in the ongoing BT associated with sepsis after injury, rats were randomized to (1) 30% burn injury with Pseudomonas wound infection (BI), (2) BI + fluid resuscitation (BI + Fluid), (3) BI after allopurinol pretreatment to inhibit xanthine oxidase (BI + Allo), or (4) BI after azapropazone pretreatment to inhibit neutrophil degranulation (BI + Aza). On postburn days (PBD) 1, 4, and 7, animals were studied for evidence of BT and intestinal lipid peroxidation. BI + Fluid, BI + Allo, and BI + Aza significantly (p less than 0.05) reduced rates of BT and ileal lipid peroxidation acutely after thermal injury (PBD 1) compared to BI. All four groups had equally high rates of BT associated with the onset of sepsis (PBDs 4 and 7), without evidence of further intestinal lipid peroxidation. These data indicate that the chronic gut barrier failure associated with sepsis after injury occurs independently of continued intestinal ischemia.

Animals↗
PubMed1991

Splanchnic vasoconstriction and bacterial translocation after thermal injury.

Gut barrier failure and bacterial translocation (BT) after thermal injury may result from splanchnic vasoconstriction and intestinal ischemia. The role of the renin-angiotensin system in intestinal blood flow and BT after thermal injury was studied by pretreatment with the angiotensin-converting enzyme (ACE) inhibitor enalapril in Wistar rats before sham or 30% scald burn. Adequacy of ACE inhibition was documented by the absence of a hypertensive response to angiotensin I, and intestinal blood flow was determined using 51Cr-labeled microspheres. Small bowel blood flow was decreased by 46% at 4-h postburn (P less than 0.05) in untreated burned animals despite maintenance of normal cardiac index but returned to baseline levels by 24 h after injury. Enalapril pretreatment resulted in maintenance of small bowel blood flow after thermal injury and was associated with a significantly reduced incidence of BT (20% vs. 75% in untreated burned animals, P less than 0.01). These findings further implicate intestinal ischemia in the etiology of gut barrier dysfunction after thermal injury, mediated in part by activation of the renin-angiotensin system.

Animals↗
PubMed1990

[Penile cancer].

We review the literature on penis cancer. The disease is rare and most of the cumulative experience is reported in retrospective series. Multi-institutional international collaboration will be needed for prospective studies of certain facets of this disease which are at present controversial. Suggested areas of research are how to treat early invasive tumours, the diagnosis and treatment of inguinal metastases, the improvement of radiotherapy techniques, the development of effective chemotherapy and effective combinations of therapies. This will potentially lead to a more sparing of organs. It is also necessary to study palliation, and aspects of quality of life. The incidence may be further reduced by educating the public about the condition and about genital hygiene, including the necessity for the early treatment of phimosis.

Carcinoma↗
PubMed1990

Cytokine production in a model of wound healing: the appearance of MIP-1, MIP-2, cachectin/TNF and IL-1.

Macrophages are essential for normal wound repair and many of their effects on healing wounds are likely to be mediated by the secretion of cytokines. This study examines the appearance of messenger RNA (mRNA) for cachectin/tumor necrosis factor (TNF), IL 1, and macrophage inflammatory proteins 1 and 2 (MIP-1 and MIP-2), as well as the mature peptides, in a model of wound healing using wound chambers. RNA for all four cytokines can be detected in wound inflammatory cells by polymerase chain reaction amplification throughout the first 7 days. Cachectin/TNF and IL 1 protein levels peaked on the first day after wound chamber implantation, and MIP-1 and MIP-2 were detected only on day 3. The data suggest that these cytokines participate in the early inflammatory response to wounding.

Animals↗
PubMed1990

Investigation, treatment and prognosis of bronchial carcinoma in the Yorkshire Region of England 1976-1983.

We studied all cases presenting during life with carcinoma of the bronchus and registered at the Yorkshire Regional Cancer Registry 1976-1983. During this period fibreoptic bronchoscopy became more widely available in the region, and multiple drug chemotherapy became first line treatment for small cell carcinoma. Although there was little change in the overall incidence of lung cancer during the study period, the proportion of females increased by 4.8% and the mean age at presentation rose by 2.3 years. The histological confirmation rate rose by 29% from 45% to 58%. The proportion of patients with small cell carcinoma treated by chemotherapy increased from 17% to 39%. With this exception therapeutic intervention rates were unaltered. The prognosis of patients with small cell carcinoma treated by chemotherapy improved, particularly so for those less than 60 years. There was a consistent trend for an overall improvement in survival in other groups, and this was significant for those aged 70 and over where it appeared to be related to more appropriate management of squamous cell carcinoma. We conclude from this regional study that increased diagnostic activity in District General Hospitals has allowed an improvement in prognosis both for patients with small cell carcinoma treated by chemotherapy, and in patients over 70 with non-small cell cancer. These trends can be expected to continue over the next few years.

Aged↗