Regulation of CD59 expression on K562 cells: effects of phorbol myristate acetate, cross-linking antibody and non-lethal complement attack.

CD59 is the major membrane attack complex of complement (MAC) inhibiting protein on human cells. Its regulation is therefore an important factor in determining the fate of cells at sites of complement activation. We have chosen the K562 erythroleukaemia cell line as a model for studies of the regulation of CD59 expression, because it has previously been reported that phorbol 12-myristate 13-acetate (PMA) caused a 15-fold up-regulation of CD59 mRNA in these cells, implying a substantial capacity for CD59 synthesis. However, no assessment of CD59 protein expression was made in these studies. We show here that surface expression of CD59, as assessed by flow cytometry, was increased four-fold over a 16-hr incubation with PMA, whereas surface expression of decay-accelerating factor (DAF) (CD55) and membrane cofactor protein (MCP) (CD46) was not altered. The newly expressed CD59 was functionally active and anchored through glycosyl-phosphatidylinositol (GPI). Increased expression was dependent upon de novo protein synthesis. CD59 released into cell supernatant was also increased seven-fold by PMA, this 'secreted' CD59 retained its GPI anchor. Non-lethal complement attack did not alter CD59 expression but antibody cross-linking of CD59 caused a rapid loss of the CD59-antibody complexes. However, CD59 was quickly restored to pre-attack levels. This rapid restoration was not dependent upon protein synthesis, suggesting release from preformed stores.     

Are clinical differences between black and white stroke patients caused by variations in the atherosclerotic involvement of the arterial tree?

The differences in site and degree of atherosclerotic involvement of various vascular beds and their clinical significance are emphasised in a study of 304 black stroke patients. Detailed clinical examinations, computed tomography (CT), gated blood pool studies, echocardiography and ECG were performed and autopsy studies carried out. CT of the brain showed that non-haemorrhage, i.e. ischaemic lesions, accounted for 71.2% of strokes, a similar figure to that found in white stroke patients. However, carotid bruits (0.62%) and peripheral vascular disease (0.9%) followed by transient ischaemic attacks (1.9%) were found to be uncommon. Similarly, ischaemic heart disease (6.9%) appeared to be less common than the incidence in reported white stroke patients. In 30 patients who came to autopsy, the maximum degree of atherosclerotic stenosis of the extracranial carotid arteries was 21.7% of the lumen diameter. The differences in the site and degree of atherosclerosis in blacks not only give rise to differences in the clinical features of stroke patients but may have an important bearing on their investigation, management and prognosis.     

Nutrition and aging: nutritional status of "apparently healthy" elderly (Dutch nutrition surveillance system)

In a nationwide survey the nutritional status was assessed of 539 apparently healthy, independently living elderly aged 65-79 years. Anthropometric data showed no energy deficits. The prevalence of anemia was 4 and 1% among men and women, respectively. Many elderly showed a low level of 25-hydroxyvitamin D in plasma (less than 31 nmol/L: men 35%; women 43%), indicating a marginal status. Although the prevalence of low blood levels of folate, pyridoxal-5'-phosphate, and total carotenoids was higher among the elderly than among younger adults, clear (clinical) signs of nutritional deficiencies were not observed. Prevalence of obesity (13%), hypercholesterolemia (38%), and hypertension (63%) was found to be high, the percentages being higher for women than for men. Several indicators of the nutritional status appeared to differ among age groups. It is concluded that few differences can be considered as being due to physiological aging, which finding should be reflected in reference values for elderly people.     

Rapid determination of benzalkonium chloride in pharmaceutical preparations with flow injection liquid-liquid extraction

Benzalkonium chloride was assayed by on-line extraction of the benzalkonium ion with picrate to chloroform. The absorbance of picrate was measured. The extractions were performed with a home-made flow injection extraction unit. Calibration curves (1.5-180 x 10(-4)% w/v) were straight lines (r = 0.9993) and the relative standard deviation of a series of injections was less than or equal to 2%. Pharmaceutical benzalkonium preparations, containing xylometazoline, timolol, phenylephrine or carbachol could also be assayed. The method was compared with a modified HPLC assay.     

Early morphogenesis of persistent hyperplastic tunica vasculosa lentis and primary vitreous. A transmission electron microscopic study

This report provides transmission electron microscopic observations on the early pathogenesis of persistent hyperplastic tunica vasculosa lentis/persistent hyperplastic primary vitreous (PHTVL/PHPV) in affected canine fetuses at days 28-44 postcoitum. The retrolental tissue by which this anomaly is characterized consists of loosely arranged fibroblasts in a randomly oriented meshwork of collagenous fibrils. Some of these cells contain melanosomes at day 44. In one day-44 eye, cells of neuroectodermal origin (Müller cells; fibrous astrocytes) were observed. From day 37 onward, the posterior subcapsular part of the lens contains rounded, increased intercellular spaces, resembling vacuoles, which deform the shape of the lens fibers. The posterior lens capsule develops normally until day 30. From day 35 onward the capsule has an amorphous ultrastructure, as opposed to the clearly laminated ultrastructure in reference eyes at day 35. In addition, the capsule's thickness increases until day 35, and, instead of growing thicker, decreases thereafter. Based on these results, it is hypothesized that a primary metabolic disorder in the lens fibers, subsequently leading to the formation of an abnormal posterior lens capsule, constitutes the primary defect in the sequence of events leading to PHTVL/PHPV.     

The Relationship Between Quantitative MRI and Neuropsychological Functioning in Temporal Lobe Epilepsy

Summary: Purpose: Quantitative MRI techniques provide an unparalleled opportunity to examine in vivo the relationship between the extent and laterality of hippocampal pathology and associated neuropsychological deficits. The purpose of this study was to examine the nature of the relationship between quantitative measures of hippocampal pathology and neuropsychological measures, using a multivariate approach. Methods: We examined the relationship between two MRI measures of hippocampal structure; hippocampal volumes (HCvol) and T2 relaxation times (HCT2), and memory performance, in 80 presurgical temporal lobe epilepsy patients. Results: As a group, patients with left hippocampal sclerosis (LHS) performed more poorly that those with right hippocampal sclerosis (RHS) on immediate and delayed prose recall. In the group as a whole, right hippocampal volume was significantly correlated with the delayed recall of a complex figure. None of the verbal memory test scores were significantly correlated with the right or left HCvol or HCT2 measures. However, stepwise multiple regression analyses indicated that up to a third of the variation in specific test scores could be explained by the quantitative MRI hippocampal measures in conjunction with chronological age, and age at onset of habitual epilepsy. Left hippocampal measures explained 24% of the variance in the story-recall tasks, while right hippocampal measures explained 18% of the variance in a design-learning task and 32% of the variance in a figure-recall task. Conclusions: Our results provide some support for the lateralised model of material specific memory deficits, but suggest that a number of demographic and epilepsy-related factors may interact with the extent and laterality of hippocampal pathology in shaping the nature of the associated neuropsychological deficit.     

Islet cell carcinomas of the pancreas: a twenty-year experience

Unlike its lethal exocrine counterpart, islet cell carcinoma of the pancreas is an indolent neuroendocrine neoplasm. The majority of these tumors are hormonally active. When functioning, a number of clinical syndromes (for example, hyperinsulinism, Zollinger-Ellison and Cushing's syndromes) may be evident. Fifty-eight patients surgically treated between 1965 and 1984 were retrospectively analyzed. The purpose of this study was to determine the distribution of functioning versus nonfunctioning tumors and the response to type of therapy. Mean postoperative follow-up was 7.4 years. Survival and prognostic indices were calculated by the Kaplan-Meier method and compared with log-rank tests. Of the group, 54% had functioning and 46% nonfunctioning tumors. Gastrinomas were the most common functioning tumors encountered (19%). Of interest was the finding that nonfunctioning tumors increased steadily during the last 15 years of the study (25% to 65%). Curative resections were performed in 15 (26%) and noncurative procedures in 43 patients (74%), with an overall operative mortality rate of 3%. Symptomatic improvement was achieved in 90% (curative) and 51% (noncurative). Survival at 3 years was 87% and 66% for the curative and noncurative groups, respectively (p less than 0.1), with an overall 5-year survival of 42%. The absence of hepatic metastases was a major predictor of survival at 3 years (82% vs 56%, p less than 0.05). Survival was statistically better at 3 years in those patients with gastrinomas compared with patients with nonfunctioning tumors (91% vs 58%, p less than 0.05). Although surgical cure is rare, significant long-term palliation may be achieved in a large percentage of patients with an aggressive surgical approach, occasional total gastrectomy, combination chemotherapy, H2 blockade, when indicated, and, most recently, with the new long-acting analogue of somatostatin.     

Antagonism of midazolam sedation by flumazenil: a placebo-controlled study in patients recovering from intravenous anaesthesia with high doses of midazolam

Twenty adult surgical patients were anaesthetized with high-dose midazolam and alfentanil by infusion, vecuronium, and intubated and ventilated with 50% N2O in O2. The midazolam and alfentanil infusions were stopped at the end of surgery. Residual neuromuscular blockade and ventilatory depression were antagonized and the patients extubated. In the recovery room, patients were randomly allocated to receive either flumazenil 1 mg of placebo i.v. Before, and until 2 h after injection, patients were asked to perform psychomotor tests. In addition, sedation, comprehension and orientation were scored. The flumazenil (n = 10) and the placebo (n = 10) groups were comparable. Prior to injection all patients were heavily sedated. After flumazenil all were awake within 2-3 min, but fell asleep again 15-60 min later. The improvement in test scores was sustained for a longer time. After placebo, patients awoke in 1-2 h. At 60 and 120 min, test scores in the two groups were similar. Heart rate, blood pressure and respiration rate did not change. No side-effects were observed or reported. It is concluded that flumazenil is an effective and safe antagonist of high dose midazolam, with a rapid onset but a short duration of action.