Metallothionein in human retinal pigment epithelial cells: expression, induction and zinc uptake.

The retinal pigment epithelium (RPE) plays several important roles in the continual support and renewal of photoreceptor outer segments. In the present study, we have demonstrated that RPE cells contain a low molecular weight protein with a high capacity for zinc binding that is dependent on available sulfhydryl groups. This protein is inducible by a 24 hour incubation of cultured RPE in medium supplemented with zinc, cadmium, or dexamethasone. The induction of this protein is correlated with an increased capacity for zinc-65 uptake into cultured RPE. Analysis with a cDNA probe specific for the human metallothionein II gene corroborated the existence and induction of metallothionein gene products in RPE cells. Based on these properties, we have identified this protein as metallothionein. The induction of metallothionein likely has a critical influence on the zinc economy of the RPE.     

The relationship of the transcutaneous oxygen tension, pulse waves and systolic pressures to the risk for limb amputation in patients with peripheral arterial disease and skin ulcers or gangrene.

AIM: Our aim was to determine how the risk associated with presence of low transcutaneous oxygen tension (tcPO2) for subsequent major amputation in patients with skin ulcers or gangrene and peripheral arterial disease, compares with the risks associated with low peripheral pressures and low amplitude of pulse waves. Secondly, we determined whether combination of measurements of oxygen tension with that of the pressures or pulse wave amplitude predicts amputation better than pressure, wave or oxygen tension measurements alone. METHODS: Measurements were carried out to obtain foot tcPO2, ankle and toe pressures, pressure indices, and toe pulse wave amplitude in 75 limbs with skin lesions and arterial disease of 66 patients referred to the vascular laboratory. These variables were related to the risk of a subsequent major amputation during a median time of 4.2 years, using Cox proportional hazards model. RESULTS: Low oxygen tension was associated with increased risk of amputation (relative risks 2.16 and 2.55 for tcPO2 < or = 10 mmHg and < or = 20 mmHg, respectively, P<0.05; relative risk 2.22 for tcPO2 < or = 30 mmHg, P=0.07). The relative risks associated with cutoff values of ankle and toe pressures and pressure indices varied from 2.53 (toe < or = 20 mmHg, P<0.05) to 5.83 (ankle < or = 50 mmHg, P<0.001) and the relative risk associated with low wave amplitude (< or = 4 mm) was 3.41, P<0.01. The cutoff values of tcPO2 became insignificant when included in the models together with each pressure variable or pulse amplitude separately. In contrast, wave amplitude remained significantly associated with increased risk of amputation after controlling for each pressure variable (P<0.05). CONCLUSIONS: TcPO2 < or = 10 mmHg and < or = 20 mmHg are related significantly to increased risk of amputation in patients with skin lesions and arterial disease, but these relative risks are similar in magnitude or smaller than those associated with low cutoff values of pressures, pressure indices or pulse wave amplitude. Low wave amplitude does provide significant information in addition to peripheral pressures with respect to the risk of amputation. On the other hand, low tcPO2 does not provide significant information in addition to peripheral pressures or pulse wave amplitude.     

Thrombin activity by intrinsic activation of plasma in-vitro accelerates with increasing age of the donor.

Thrombotic diseases increase in incidence with advancing years and this might be partly due to an increased propensity for fibrin formation in older individuals. Accordingly we decided to investigate whether the time taken to generate 50% thrombin activity in vitro varied with the age of the plasma donor. Coagulation was initiated in defibrinated, diluted plasma by contact activation and thrombin activity measured using the chromogenic substrate, S2238. The rate of thrombin generation was assessed by measuring the time taken to reach 50% maximal activity (T50/s). There was a highly significant negative correlation between T50 and age, T50 declining from 93 s at 19 years to 71 s at 65 years (r = -0.637, p less than 0.0001). A strong negative correlation was demonstrated between T50 and FVII level (r = -0.415, p = 0.0007) and FVIII:C level (r = -0.465, p = 0.0001). Although FVII concentration correlated with age (r = 0.307, p = 0.014) no relationship was seen between age and FVIII:C. These data suggest that coagulation rates in plasma accelerate with age.     

Verbal Working Memory and Atherosclerosis in Patients with Cardiovascular Disease: An fMRI study

BACKGROUND AND PURPOSE: Intimal-medial thickening (IMT) of the carotid wall is an accepted peripheral marker of atherosclerosis. It is associated with increased risk for myocardial infarction and stroke, and lower attention-executive-psychomotor functioning. The purpose of this study was to examine the relationship between IMT and brain activity during a verbal working memory (VWM) task in patients with cardiovascular disease (CVD). METHODS: Thirteen CVD patients underwent functional magnetic resonance imaging (fMRI) during a 2-Back VWM task, and B-mode ultrasound of the carotid arteries. IMT was calculated using an automated algorithm based on a validated edge-detection technique. The relationship between IMT and 2-Back-related brain activity was modeled using partial correlations controlling for age and small vessel disease as measured by white matter signal hyperintensities on MRI (WMH). RESULTS: Higher IMT was associated with lower 2-Back-related signal intensity and in the right middle frontal gyrus, independent of age and WMH. CONCLUSIONS: IMT may be one mechanism contributing to brain dysfunction in CVD. The blood oxygenation level-dependent (BOLD) contrast appears to be highly sensitive to peripheral vascular health as measured by IMT. Future studies should examine the sensitivity and specificity of the BOLD response for predicting cognitive decline in CVD.     

Nosocomial infections on a rehabilitation unit in an acute care hospital

In a one-year retrospective review, 138 symptomatic infections were identified in 145 admissions to a rehabilitation unit. One hundred twenty-six (91%) infections were either urinary or skin and soft tissue infections. The daily incidence of infection increased with increasing numbers of infections for infected patients. Patient factors associated with infection included male sex, young age, spinal cord injury, admission for management of decubitus ulcers or urinary infection, history of urinary infection, urologic interventions or skin breakdown, and bladder and bowel incontinence. All patients with a history of chronic urinary infection or skin breakdown developed infection. In a logistic regression model, factors that were independently associated with risk of infection in the remaining patients included sex, incontinence, chronic neurologic disease, and prior urologic interventions. This review suggests rehabilitation patients are at high risk of acquiring nosocomial infection. The subgroup of patients with the highest risk of infection are identifiable by specific characteristics.     

A novel 37-Kd adhesive membrane protein from cloned murine bone marrow stromal cells and cloned murine hematopoietic progenitor cells

The adhesion of hematopoietic progenitor cells to bone marrow stromal cells is critical to hematopoiesis and involves multiple effector molecules. Stromal cell molecules that participate in this interaction were sought by analyzing the detergent-soluble membrane proteins of GBI/6 stromal cells that could be adsorbed by intact FDCP-1 progenitor cells. A single-chain protein from GBI/6 cells having an apparent molecular weight of 37 Kd was selectively adsorbed by FDCP-1 cells. This protein, designated p37, could be surface-radiolabeled and thus appeared to be exposed on the cell membrane. An apparently identical 37- Kd protein was expressed by three stromal cell lines, by Swiss 3T3 fibroblastic cells, and by FDCP-1 and FDCP-2 progenitor cells. p37 was selectively adsorbed from membrane lysates by a variety of murine hematopoietic cells, including erythrocytes, but not by human erythrocytes. Binding of p37 to cells was calcium-dependent, and was not affected by inhibitors of the hematopoietic homing receptor or the cell-binding or heparin-binding functions of fibronectin. It is proposed that p37 may be a novel adhesive molecule expressed on the surface of a variety of hematopoietic cells that could participate in both homotypic and heterotypic interactions of stromal and progenitor cells.     

Issues in the management of behaviour disturbance as a consequence of severe head injury

The management of organic psychosocial deficit following severe head injury has been a neglected area of rehabilitation. Behavioural modification programmes are being utilised increasingly to ameliorate inappropriate behaviours within the rehabilitation framework. Patterns of organic psychosocial deficits in the head injured are described and issues in the management of behaviour disturbances and the constraints that operate in the application of psychological techniques to the population who suffer acquired brain damage are discussed.     

The potential role of the heparin-binding growth factor pleiotrophin in breast cancer

Summary We propose that the secreted protein pleiotrophin (PTN) is a major factor in the malignant progression of breast cancer. This hypothesis is based on the growth-stimulatory effects of PTN on cellsin vitro andin vivo and on its high levels of expression in 60% of tumor samples from breast cancer patients. The stimulation of proliferation and tube formation of endothelial cells by PTN suggests that it can serve as an angiogenesis factor during tumor growth. We hypothesize that PTN has the potential to support growth of breast cancer at its primary site and to enhance the ability of tumor cells to metastasize. Furthermore, we suggest that specific endocrine signals interact to regulate the expression of PTNin vitro andin vivo. Finally, we propose that understanding the functions of PTN and its hormonal regulation can lead to the development of novel therapeutic strategies for breast cancer.     

Correlation between the induction of an immediate early gene, zif/268, and long-term potentiation in the dentate gyrus.

Expression of the immediate early gene zif/268 (also termed NGFI-A, Krox 24, TIS8 and Egr-1) was investigated in awake rats following various long-term potentiation (LTP) induction protocols.zif/268 mRNA (Northern blots) and protein (immunohistochemistry) levels sharply increased following LTP, and followed a time course characteristic of other immediate early genes. When measured across 3 tetanization protocols known to produce differing degrees of LTP persistence,zif/268 induction was found to be more highly correlated with LTP duration than with the magnitude of initial LTP. These data support the hypothesis that the immediate early gene zif/268 plays a role as a third messenger in the cascade of cellular and nuclear events that govern the persistence of LTP.