Soft tissue tumours

Any soft tissue swelling beneath the deep fascia should be considered a sarcoma until proven otherwise. As the most important factor in the primary treatment of these cancers is the adequacy of the primary surgical resection, it is vital to diagnose these malignant tumours pre-operatively. The modern treatment of soft tissue sarcomas may involve all modalities, but the most important aspect of treatment of a primary localised sarcoma is wide excisional surgery preserving limb function. Radiotherapy is a vital adjunct in high-grade tumours, or in tumours whose resectability is limited either by size or anatomical proximity to vital structures. Apart from a few chemosensitive sarcomas, the role of chemotherapy is limited to treatment of metastatic disease where documented response rates are no greater than 30%. As 50% of patients with high-grade sarcomas will die from metastatic disease, improvements in survival rates will only come from improvements in response to systemic therapy. No controlled trials have shown any survival benefit for adjuvant chemotherapy, although a recent meta-analysis of published data has shown a trend to increased survival at two years. Multicentre randomised trials are ongoing. The prognosis of these lesions is highly variable, but is intimately related to the anatomical site (i.e., resectability), and also the grade and size of the tumour.     

Metabolic impact of adenovirus-mediated overexpression of the glucose-6-phosphatase catalytic subunit in hepatocytes

Glucose-6-phosphatase (G6Pase) catalyzes the hydrolysis of glucose 6-phosphate (Glu-6-P) to free glucose and, as the last step in gluconeogenesis and glycogenolysis in liver, is thought to play an important role in glucose homeostasis. G6Pase activity appears to be conferred by a set of proteins localized to the endoplasmic reticulum, including a glucose-6-phosphate translocase, a G6Pase phosphohydrolase or catalytic subunit, and glucose and inorganic phosphate transporters in the endoplasmic reticulum membrane. In the current study, we used a recombinant adenovirus containing the cDNA encoding the G6Pase catalytic subunit (AdCMV-G6Pase) to evaluate the metabolic impact of overexpression of the enzyme in primary hepatocytes. We found that AdCMV-G6Pase-treated liver cells contain significantly less glycogen and Glu-6-P, but unchanged UDP-glucose levels, relative to control cells. Further, the glycogen synthase activity state was closely correlated with Glu-6-P levels over a wide range of glucose concentrations in both G6Pase-overexpressing and control cells. The reduction in glycogen synthesis in AdCMV-G6Pase-treated hepatocytes is therefore not a function of decreased substrate availability but rather occurs because of the regulatory effects of Glu-6-P on glycogen synthase activity. We also found that AdCMV-G6Pase-treated-cells had significantly lower rates of lactate production and [3-3H]glucose usage, coupled with enhanced rates of gluconeogenesis and Glu-6-P hydrolysis. We conclude that overexpression of the G6Pase catalytic subunit alone is sufficient to activate flux through the G6Pase system in liver cells. Further, hepatocytes treated with AdCMV-G6Pase exhibit a metabolic profile resembling that of liver cells from patients or animals with non-insulin-dependent diabetes mellitus, suggesting that dysregulation of the catalytic subunit of G6Pase could contribute to the etiology of the disease.     

Neutrophil attractant protein-1 and monocyte chemoattractant protein-1 in human serum. Effects of intravenous lipopolysaccharide on free attractants, specific IgG autoantibodies and immune complexes

We recently found that normal human sera contain IgG antibodies against two chemoattractants, neutrophil attractant protein-1 (NAP-1/IL-8) and monocyte chemoattractant protein-1 (MCP-1), as well as immune complexes of these proteins. Intravenously administered LPS was reported to cause a sharp rise in serum NAP-1 concentration. Our study was designed to determine if LPS also caused an increase in MCP-1 and to measure associated changes in concentrations of antibody and immune complex. LPS caused a rise to peak within 2 to 3 h in serum concentrations of free NAP-1 and MCP-1, followed by an almost equally rapid fall toward base-line levels by about 5 h postinjection. MCP-1 concentration in sera from the 11 subjects rose to a peak of 330 +/- 52 pM. The peak value for NAP-1 was 80 +/- 11 pM. In 10 of the 11 subjects, free IgG autoantibody to MCP-1 decreased from a mean pre-LPS value of 1820 +/- 660 pM to a mean low of 53% of the respective initial values. Corresponding data for IgG anti-NAP-1 were a pre-LPS concentration of 216 +/- 7 pM, which decreased to a mean low of 44% of the respective initial values. The finding in some subjects of a rapid rise in free antibody after the nadir suggests the possibility of acute regulation of autoantibody secretion rates. Although the results suggested that LPS-induced chemoattractant combined with free antibody, serum concentrations of MCP-1-IgG or NAP-1-IgG did not increase, which points to an as yet unknown mechanism for trapping and elimination of the immune complexes.     

Small bowel transplantation: current progress and clinical application

Total parenteral nutrition (TPN) is used routinely to maintain patients with the Short Bowel Syndrome (SBS). Until recently, TPN has been the only available therapeutic modality for patients with SBS. Currently, it is the treatment of choice for such individuals and occasionally, when the loss of bowel is extensive, it may be the only way of maintaining life. Unfortunately, TPN is expensive and markedly restrains an individual's lifestyle. Despite the overall success of TPN, the numerous risks associated with its use and the many complications of having an intravenous indwelling for years have served as the stimulus for alternative treatments such as small bowel transplantation (SBT). The first attempts at small bowel transplantation in clinical medicine were by Detterling almost 25 years ago. Patient death or graft loss in these early attempts was caused by the failure to control graft rejection and/or the inability to prevent Graft Versus Host Disease (GVHD). A stimulus for renewed clinical interest in SBT was provided by Starzl et al in 1988 with a report of prolonged graft survival without graft rejection or GVHD in a patient who was the recipient of a multivisceral graft consisting of the entire small bowel and other abdominal organs. Since 1964, 78 Small Bowel transplants have been performed in humans. Several variations of the multivisceral procedure in which the liver and the small bowel constitute the major components of the graft were adopted. The longest survival has been in a child who is still alive with a working graft for more than two years, as reported by Goulet from Paris in 1989. The introduction in SBT of the new immunosuppressive agent FK 506 had provided results which are superior to those achieved with Cyclosporine A (CsA). This latter observation prompted the Pittsburgh group to initiate a large series of isolated and composite intestinal grafts. The remarkable results have demonstrated the clinical utility of intestinal transplantation. This paper will try to summarize the history of the small bowel transplantation until the end of the year 1992, with the current progress in use today.     

Comparison of prototype and rote instruction of English names for Chinese visual characters

This study compared prototype and rote instruction of English names for Chinese visual characters. In the prototype condition, participants were taught the meaning of the prototype that served as the distinctive feature of multicomponent characters. In the rote condition, participants traced the character and wrote its translation. Participants learned more rapidly and maintained more words in the prototype condition.     

Flash photolysis of the carbon monoxide compounds of wild-type and mutant variants of cytochrome bo from Escherichia coli

The carbon monoxide compounds of the fully reduced and mixed valence forms of cytochrome bo from Escherichia coli were laser photolysed under anaerobic conditions at room temperature. The carbon monoxide recombined with characteristic rate constants of 50 s-1 or 35 s-1 in the fully reduced and mixed valence forms, respectively. Rates of CO recombination with the fully reduced enzyme were examined in a variety of mutant forms of cytochrome bo, produced by site-directed mutagenesis. A method was developed to deconvolute cytochromes bo and bd, leading to some reassessment of histidine ligands to the metals. Significant changes in the rate constant of recombination of carbon monoxide occurred in many of these mutants and these results could be rationalised generally in terms of our current working model of the folding structure of subunit I. In the mixed valence form of the enzyme the transient photolysis spectra in the visible region are consistent with a rapid electron redistribution from the binuclear centre to the low-spin haem. This electron transfer is biphasic, with rate constants of around 10(5) and 8000 s-1. The process was also examined in the His-333-Leu mutant, in which a putative histidine ligand to CuB is replaced by leucine, and which results in the loss of the CuB. It appeared that rapid haem-haem electron transfer could still occur. The observation that CuB is apparently not required for rapid haem-haem electron transfer is consistent with the recently proposed model in which the two haems are positioned on opposite sides of transmembrane helix X in subunit I of the oxidase.     

Association of herpes zoster ophthalmicus with acquired immunodeficiency syndrome and acute retinal necrosis

We conducted a review to investigate the prevalence of human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS), in patients with herpes zoster ophthalmicus, as well as the incidence of acute retinal necrosis after herpes zoster ophthalmicus. All charts of patients seen at our institution between 1987 and 1992 with a primary diagnosis of herpes zoster ophthalmicus were reviewed. Of 112 patients with herpes zoster ophthalmicus, 29 (26%) had HIV or AIDS. All these patients were younger than 50 years at the time of diagnosis. Five of 29 (17%) immunocompromised patients had acute retinal necrosis after herpes zoster ophthalmicus. No acute retinal necrosis was identified in the nonimmunocompromised patients after herpes zoster ophthalmicus. We recommend that all patients younger than 50 years who have herpes zoster ophthalmicus at initial examination be tested for HIV. Additionally, HIV-infected patients should be monitored closely after herpes zoster ophthalmicus for development of acute retinal necrosis. Long-term oral prophylactic as well as initial high-dose intravenous acyclovir may be appropriate in HIV-infected individuals with herpes zoster.