The surface-charge asymmetry and dimerisation of cytochrome c550 from Paracoccus denitrificans--implications for the interaction with cytochrome c peroxidase

The neuroprotective efficacy of YM872, a novel, highly water-soluble alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist, was investigated in rats subjected to permanent occlusion of the left middle cerebral artery. The rats were assessed either histologically or neurologically 24 hr or 1 wk after ischemia. YM872 was intravenously infused for either 4 or 24 hr at dose rates of 0 to 20 mg/kg/hr starting 5 min after ischemia to examine the effect of prolonged treatment. YM872 was then infused at 20 mg/kg/hr beginning 0 to 4 hr after ischemia to determine the efficacy time window. Additionally, a 20 mg/kg/hr dose rate of YM872 was infused for 4 hr in single day- or 5-day repetitive-administrations to evaluate long-term benefits of the drug. YM872 significantly reduced infarct volume in both 4- and 24-hr treatment groups measured 24 hr after ischemia. No difference was observed in the degree of protection between length of infusion. Significant neuroprotection was maintained even when drug administration was delayed up to 2 hr after ischemia. A single YM872-administration significantly improved neurological deficit and reduced infarct volume (30%, P <.01) measured 1 wk after ischemia. YM872 treatment did not induce such adverse effects as physiological changes, serious behavioral abnormalities or nephrotoxicity. These data suggest that the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor plays a crucial role in the progression of neuronal damage in the early phase of ischemia and that YM872 may be useful in treating acute ischemic stroke.     

MEMD, a new cell adhesion molecule in metastasizing human melanoma cell lines, is identical to ALCAM (activated leukocyte cell adhesion molecule)

From a differential mRNA display comparing a non- and a highly metastasizing human melanoma cell line, we isolated and characterized memD. memD is preferentially expressed in the highly metastasizing melanoma cell lines of a larger panel. The encoded protein, MEMD, is identical to activated leukocyte cell adhesion molecule (ALCAM), a recently identified ligand of CD6. ALCAM is involved in homophylic (ALCAM-ALCAM) and heterophylic (ALCAM-CD6) cell adhesion interactions. We have studied MEMD/ALCAM cell-cell interactions between human melanoma cells. The expression of this cell adhesion molecule not only correlates with enhanced metastatic properties and with aggregational behavior of human melanoma cells as tested by FACS analysis, but transfection experiments also make clear that MEMD/ALCAM expression is essential for cell-cell interaction of the investigated human melanoma cells. As the melanoma cell lines analyzed are all CD6 negative, these results strongly suggest that MEMD/ALCAM is an adhesion molecule mediating homophylic clustering of melanoma cells. MEMD/ALCAM expression is not restricted to subsets of leukocytes and melanoma cells, it can also be found in healthy organs and in several other malignant tumor cell lines. Besides, MEMD/ALCAM is also expressed in cultured endothelial cells, pericytes and melanocytes, in xenografts derived from the radial and vertical growth phase and in 4 of 13 melanoma metastasis lesions. The potential role is discussed of MEMD/ALCAM mediated cell-cell interactions in migration of mobile cells (ie, activated leukocytes, metastasizing tumor cells) through tissues.     

The association of increasing dietary concentrations of fish oil with hepatotoxic effects and a higher degree of aorta atherosclerosis in the ad lib.-fed rabbit

The long-term effects of consumption of marine long-chain n-3 polyunsaturated fatty acids (PUFA) on atherosclerosis in the rabbit were examined. Female Dutch rabbits were fed purified diets, containing 40 energy% total fat, for a period of 2.5 years. To study the dose response relationship between fish oil intake and atherosclerosis, four diets were formulated with fish oil levels being 0, 1, 10 and 20 energy%. A fifth and sixth group were fed an alpha-linolenic acid-(C18:3, n-3) and linoleic acid-(C18:2, n-6) rich diet, respectively. Every 6 weeks, blood samples were taken for determination of clinical chemical parameters, triacylglycerol and total cholesterol levels. Feeding 10 and 20 energy% fish oil containing diets, resulted in an increase of liver enzymes (AST, ALT and ALP). Histological evaluation of the liver also revealed adverse effects of fish oil containing diets. Triacylglycerol blood levels were similar in all groups, and remained constant throughout the study. Total cholesterol levels in blood was significantly lower in the animals fed a linoleic acid-rich diet, as compared with the other five groups. An n-3 long-chain PUFA concentration dependent increase in aorta plaque surface area was observed in the fish oil groups. A significant positive relationship was found between the group mean score for severity of liver pathology and the aorta plaque surface area. These results indicate that the long-chain n-3 polyunsaturated fatty acids in fish oil may be hepatotoxic to the herbivorous rabbit, which may interfere with the outcome of atherosclerosis studies. This finding necessitates the exclusion of liver pathology in experimental studies on atherosclerosis in animal models.     

Detection of response to chemotherapy using positron emission tomography in patients with oesophageal and gastric cancer

BACKGROUND: The aim of the study was to determine whether 2-[18F]-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) could detect response to chemotherapy in patients with oesophageal and gastric cancer. METHODS: Fourteen patients underwent imaging before and after chemotherapy using FDG-PET. Computed tomography (CT), dysphagia scores and weight changes were used for comparison of evidence of response. Tumour to liver ratios (TLRs) and influx constants for FDG (K) were used for quantification purposes. RESULTS: Thirteen of 14 lesions were successfully imaged before therapy. Changes were seen in all follow-up scans, ranging from a complete response to a 15 per cent increase in tumour FDG uptake. Response was demonstrated by CT in four patients; all four had large reductions in FDG uptake after chemotherapy. Two patients with an increase in FDG uptake reported no improvement in dysphagia and continued to lose weight during therapy. CONCLUSION: Changes in tumour FDG uptake were seen in all tumours after chemotherapy. FDG-PET may have a role to play in the assessment of patients with upper gastrointestinal malignancy receiving chemotherapy.     

CGRP-beta unlike CGRP-alpha has no osteogenic stimulatory effect in vitro

The purpose of this study is to test whether CGRP-beta has an osteogenic stimulating effect, as does CGRP-alpha, on rat bone marrow cells in vitro. CGRP-beta in different doses was added daily to bone marrow white cells, which were harvested from rats, then seeded onto a previously prepared layer of fibroblasts. CGRP-alpha in different doses was used as a positive control. Fourteen days after the start of the experiment, there was no statistical difference in the number of bone colonies between the control and CGRP-beta dishes. The CGRP-alpha dishes demonstrated an increase in the number of colonies with an increase of peptide dose.     

Bond strengths of the adhesive resin-amalgam interface

Generalized (diffuse) plane xanthoma (GPX) is a normolipaemic xanthomatosis that is very frequently associated with a haematological disorder, and especially with monoclonal gammapathies, which it may precede by several months or years. Here, we report a case of GPX associated with idiopathic Bence-Jones proteinuria, a very rare type of monoclonal gammopathy of undetermined significance. To our knowledge, this association has not been previously described.     

Total colpocleisis for vaginal eversion

OBJECTIVE: This report describes a technique for total colpocleisis performed on women with posthysterectomy vaginal eversion and presents the outcome of this surgery. STUDY DESIGN: Thirty-three women, aged 51 to 94 years (78.1 +/- 8.8, average +/- SD) with vaginal eversion were treated with total colpocleisis. Twenty-four women had previously undergone a total of 40 operations for prolapse, and many had a massive prolapse with scarring and ulceration. Five women had stress incontinence, and an additional 12 had poor urethral support without stress incontinence. In association with colpocleisis, 14 had suburethral plication of the endopelvic fascia; two, needle suspensions; and one, a pubovaginal sling. Three had a perineorrhaphy. RESULTS: Operations lasted from 30 to 205 minutes (101 +/- 33.4, average +/- SD), and the estimated blood loss ranged from 20 to 750 ml (206 +/- 171, average +/- SD). No operative complications occurred. Postoperatively, congestive heart failure developed in two women and one had pneumonia; all illnesses resolved with appropriate therapy. There were no complications at the operative site. Average follow-up was 35 (+/-48) months. All women were initially cured of the vaginal eversion. Recurrent eversion developed in one woman 1 year after surgery and was successfully treated with repeat colpocleisis. Of five women with preoperative stress incontinence, four were cured and one lost to follow-up. No new stress incontinence occurred. CONCLUSION: Total colpocleisis is an effective operation for the treatment of vaginal eversion in selected situations. When defective urethral support is corrected at the time of the operation, postoperative incontinence is not usually a problem.     

Noise, physiology, and human performance: the potential role of effort

The equine fetlock joint cavity shows ten pouches. The dorsal recess, which is oriented to the proximal side, is separated from those three pouches, which show to the distal direction, by several capsular folds. These folds are documented by means of sagittal sections through the fetlock joint. A medial/lateral recess is covered by the deep part of the collateral ligament of the fetlock joint. The collateral ligaments as well as the sesamoidean collateral ligaments are closely connected with the joint capsule, from which two capsular folds are separated. Between the part of the sesamoidean collateral ligament, that inserts to the metacarpus/metatarsus and the part that inserts to the proximal phalanx, the fetlock joint cavity pouches as Recessus palmaris/plantaris distalis medialis/lateralis. The palmar/plantar distal pouch, which lies in the median line, is covered by the Ligamentum sesamoideum rectum. This recess is narrowed down by the cruciated sesamoidean ligaments. The dominant palmar/plantar proximal recess is subdivided into several small pouches by strings or bands of the joint capsule, which can already be seen with an unaided eye.