The pathophysiology of cancer-related fatigue: current controversies.

Fatigue is one of the most common and debilitating cancer symptoms, and is associated with impaired quality of life. The exact pathophysiology of cancer-related fatigue (CRF) is poorly understood, but in any individual, it is likely multifactorial and involves inter-related cytokine, muscular, neurotransmitter, and neuroendocrine changes. Underlying CRF mechanisms proposed include central and peripheral hypotheses. Central mechanisms include hypotheses about cytokine dysregulation, hypothalamic-pituitary-adrenal-axis disruption, circadian rhythm disruption, serotonin, and vagal afferent nerve function while peripheral mechanisms include hypotheses about adenosine triphosphate and muscle contractile properties. Currently, these hypotheses are largely based on evidence from other conditions in which fatigue is characteristic. The purpose of this article is to provide a narrative review of the literature and present the current controversies in the pathophysiology of CRF, particularly in relation to central and peripheral hypotheses for CRF. An understanding of pathophysiology may facilitate direct and simple therapeutic interventions for those with cancer.

Malignant melanoma of the gall bladder--does primary melanoma exist?

Although cases of both primary and metastatic malignant melanoma of the gall bladder have been reported, and the occurrence of metastasis to the gall bladder is well recognized, it is still far from clear as to whether a primary melanoma of the gall bladder is a definite entity in itself. Criteria which have been used to make the diagnosis of primary melanoma include the size and shape of the tumor, the presence of junctional activity within the tumor and the lack of another obvious primary site. We present a case of definite metastatic melanoma of the gall bladder however which demonstrates all these primary melanoma features. This must call into doubt the validity of these criteria as diagnostic aids, and ultimately the question remains--does primary melanoma of the gall bladder actually exist?

An alternative to synthetic aortic grafts using jejunum.

Synthetic materials currently used for arterial grafts can provoke serious complications such as infection, rejection, and incomplete reendothelialization. Porcine small intestinal submucosa (SIS) allografts (homografts) may not share these disadvantages yet still may provide an effective graft alternative. This study was designed to provide additional information concerning the performance of this material when used as an allo-patch graft. A porcine model was selected to enable hemodynamic comparisons to the adult human physiology. Slaughterhouse small intestine was used to prepare the SIS graft material. A well-vascularized section ofjejunum was resected, rinsed, and maintained in 0.9% NaCl solution containing 10% gentamicin. The graft was prepared by removing the serosal layer, inverting the material, and discarding the mucosal surface in a similar manner. The remaining submucosa and stratum compactum constituted the graft material and was subdivided into sizes from 1.5 to 3.0 cm2 tacked to foil for manageability, and was returned to the gentamicin solution. The surgery was initiated with a femoral arterial line in the anesthetized swine, followed by isolation and preparation of the infrarenal aorta for grafting. Cross-clamps were applied and a 1.0 x 1.5-cm section of aortic wall was resected. Two sides of allograft were freed from the foil and sewn into the aorta. Then the remaining sides were removed from the foil and final graft placement was completed. The graft was harvested at postoperative day 28 and presented for microscopic examination. Results confirmed that reendothelialization with neovascularization had occurred during this interval.

Sensory architectures for biologically inspired autonomous robotics.

Engineers have a lot to gain from studying biology. The study of biological neural systems alone provides numerous examples of computational systems that are far more complex than any man-made system and perform real-time sensory and motor tasks in a manner that humbles the most advanced artificial systems. Despite the evolutionary genesis of these systems and the vast apparent differences between species, there are common design strategies employed by biological systems that span taxa, and engineers would do well to emulate these strategies. However, biologically-inspired computational architectures, which are continuous-time and parallel in nature, do not map well onto conventional processors, which are discrete-time and serial in operation. Rather, an implementation technology that is capable of directly realizing the layered parallel structure and nonlinear elements employed by neurobiology is required for power- and space-efficient implementation. Custom neuromorphic hardware meets these criteria and yields low-power dedicated sensory systems that are small, light, and ideal for autonomous robot applications. As examples of how this technology is applied, this article describes both a low-level neuromorphic hardware emulation of an elementary visual motion detector, and a large-scale, system-level spatial motion integration system.

Papillary apocrine fibroadenoma of the vulva.

An unusual papillary tumour of the vulva is described which exhibits apocrine features, as currently defined. The tumour has areas which resemble sclerosing adenosis of the breast and also exhibits mucinous and sebaceous differentiation. A review of the literature reveals a small number of similar lesions of the vulva. Many of these have been classified as lesions of ectopic breast tissue. In the absence of associated normal breast lobules it is impossible to differentiate these from lesions arising from apocrine sweat glands. This papillary apocrine fibroadenoma may represent a distinct cutaneous tumour occurring in this site.

Decrease in Three Messenger RNA Species Coding for Chloroplast Proteins in Leaves of Barley Infected with Erysiphe graminis f. sp. hordei.

Cloned hybridization probes have been used to investigate the effect of infection of susceptible Hordeum vulgare cv Prior by Erysiphe graminis f. sp. hordei on the abundance of host mRNAs coding for the large (LSU) and precursor to the small (SSU) subunits of ribulose 1,5-bisphosphate carboxylase/oxygenase and the rapidly metabolized 32kD thylakoid protein (32kDP). In leaf RNA preparations from control (noninoculated) plants the amount of mRNA for the LSU and SSU declined from 7 to 11 days after sowing, whereas that for the 32kDP increased over this period. Following inoculation at 6 days after sowing, the abundance of each of the mRNA species was significantly reduced below that of controls at 1, 3, and 5 days later. Results indicate that infection causes a rapid and extensive reduction in host mRNA species coding for proteins with important photosynthetic functions.

Measuring the quantity and activity of mitochondrial electron transport chain complexes in tissues of central nervous system using blue native polyacrylamide gel electrophoresis.

Mitochondrial dysfunction and degeneration are associated with many neurodegenerative disorders. A dysfunctional mitochondrial electron transport chain (ETC) impairs ATP production and accelerates the generation of free radicals. To evaluate mitochondrial function, reliable methods are needed. Conventional spectrophotometric assays may not eliminate interference from nonspecific enzyme activities and do not measure quantities of specific ETC complexes. Blue native polyacrylamide gel electrophoresis (BN-PAGE) has been used to resolve mitochondrial ETC complexes. Combined with histochemical staining, it has also been applied to measure ETC enzyme activities in muscles. The current study is to determine (1) whether BN-PAGE can be used to detect ETC complexes from different regions of the central nervous system (CNS) and (2) the quantitative range of BN-PAGE in measuring the amounts and activities of different ETC complexes. By systematically varying the protein amount and the time of histochemical reactions, we have found linear ranges comparable to spectrophotometric assays for measuring enzyme activities of several ETC complexes. In addition, we found linear ranges for measuring protein quantities in several ETC complexes. These results demonstrate that BN-PAGE can be used to measure the amount and activity of the ETC enzymes from the nerve tissues and, thus, can be applied to evaluate the functional changes of mitochondria in neurodegenerative disorders.

Sequences of the coat protein gene of five peanut stripe virus (PStV) strains from Thailand and their evolutionary relationship with other bean common mosaic virus sequences.

The coat protein gene and part of the 3' non-coding region of five strains of peanut stripe virus (PStV) from Thailand have been cloned and sequenced. Phylogenetic comparisons of these strains, known as T1, T3, T5, T6 and T7, and related sequences showed that these strains are indeed strains of PStV. Further, PStV strains appear to be related to each other according to their geographic origin. That is, the Thai strains are more closely related to each other than they are to strains from the USA or Indonesia, despite the variety of symptoms caused by these strains and the overlap of symptom types between the strains from different locations. Like other PStV strains, PStV-Thai can be considered strains of bean common mosaic virus (BCMV) but can be distinguished from bean-infecting strains of BCMV and blackeye cowpea mosaic virus (B1CMV) through sequence and host range. No evidence was found that PStV-Thai strains, unlike PStV-Ib, are recombinants of PStV and B1CMV, although the T3 strain may be a recombinant of different PStV sequences. Phylogenetic analyses of viruses of the BCMV group suggest that acquisition of the ability to infect peanut may have occurred only once.

Genetic engineering of grain and pasture legumes for improved nutritive value.

This review describes work aimed at the improvement of the nutritive value of grain and forage legumes using gene transfer techniques. Two traits which are amenable to manipulation by genetic engineering have been identified. These are plant protein quality and lignin content. In order to increase the quality of protein provided by the legume grains peas and lupins, we are attempting to introduce into these species chimeric genes encoding a sunflower seed protein rich in the sulphur-containing amino acids methionine and cysteine. These genes are designed to be expressed only in developing seeds of transgenic host plants. Chimeric genes incorporating a similar protein-coding region, but different transcriptional controls, are being introduced into the forage legumes lucerne and subterranean clover. In this case the genes are highly expressed in the leaves of transformed plants, and modifications have been made to the sunflower seed protein-coding sequences in order to increase the stability of the resultant protein in leaf tissue. Another approach to increasing plant nutritive value is represented by attempts to reduce the content of indigestible lignin in lucerne.

Ankylosing spondylitis and HLA-B27: restriction fragment length polymorphism and sequencing of an HLA-B27 allele from a patient with ankylosing spondylitis.

Two groups of patients with ankylosing spondylitis (AS) from England and Poland were examined for restriction fragment length polymorphisms (RFLPs) associated with the disease. No preferential association was found between the 9.2 kb PvuII fragment in HLA-B27 positive patients with AS compared with HLA-B27 healthy subjects as had been previously reported. In the English group, however, a 14 kb PvuII fragment was more common in HLA-B27 positive subjects with AS than in normal controls. Also 4.6 and 3.7 kb PvuII fragments were more prevalent in subjects without AS than in the group with AS, but these results were confined to the English group. Furthermore, the sequence of an HLA-B*2705 gene isolated from a patient with AS was examined, and no significant differences were found compared with the sequence isolated from a healthy subject. There do not seem to be significant genetic differences in the coding or in the regulatory region in HLA-B27 alleles, in subjects with or without AS.