Integral membrane proteins carry out some of the most important functions of living cells, yet relatively few details are known about their structures. This is due, in large part, to the difficulties associated with preparing membrane protein crystals suitable for X-ray diffraction analysis. Mechanistic studies of membrane protein crystallization may provide insights that will aid in determining future membrane protein structures. Accordingly, the solution behavior of the bacterial outer membrane protein OmpF porin was studied by static light scattering under conditions favorable for crystal growth. The second osmotic virial coefficient~B 22 ! was found to be a predictor of the crystallization behavior of porin, as has previously been found for soluble proteins. Both tetragonal and trigonal porin crystals were found to form only within a narrow window of B 22 values located at approximately Ϫ0.5 to Ϫ2 ϫ 10 Ϫ4 mol mL g Ϫ2 , which is similar to the "crystallization slot" observed for soluble proteins. The B 22 behavior of protein-free detergent micelles proved very similar to that of porin-detergent complexes, suggesting that the detergent's contribution dominates the behavior of protein-detergent complexes under crystallizing conditions. This observation implies that, for any given detergent, it may be possible to construct membrane protein crystallization screens of general utility by manipulating the solution properties so as to drive detergent B 22 values into the crystallization slot. Such screens would limit the screening effort to the detergent systems most likely to yield crystals, thereby minimizing protein requirements and improving productivity.Keywords: cloud point; membrane protein crystallization; porin; protein-detergent complex; second osmotic virial coefficient; static light scattering Knowledge of a protein's three-dimensional~3D! structure is critical for any thorough understanding of its function. Consequently, much effort has been devoted to the problem of structure determination, and the number of proteins of known structure has grown explosively in the past several decades. Now that complete genomic sequences are becoming available for many organisms, structural biologists are redoubling their efforts and are crafting structural proteomics initiatives aimed at keeping pace with the flood of sequence information~Terwilliger et al., 1998!. However, the explosion in our knowledge of protein structure has not extended to integral membrane proteins. Even though 20-30% of the open reading frames found in a genome are likely to encode membranebound proteins~Wallin & von Heijne, 1998!, far fewer than 1% of the structures found in the Protein Data Bank represent membrane proteins. This disparity persists despite tremendous interest in membrane protein structure, fueled by the critical biological functions of these molecules and by their importance as drug targets.The relative lack of information about membrane protein structure can be traced directly to the technical difficulties associated w...

We describe two adult patients who presented with acute cerebral infarction and were found to have a hypercoagulable state due to nephrotic syndrome. One patient had a deficiency of free protein-S. The other patient had a pulmonary embolus 4 months after the stroke. Our cases demonstrate that the hypercoagulable state associated with nephrotic syndrome can be associated with cerebral arterial thrombosis and infarction in adults. Examination of the urine remains an important part of the evaluation of patients with recent stroke. We recently studied two patients who presented with acute ischemic stroke and were subsequently found to have a hypercoagulable state resulting from nephrotic syndrome. Case Reports Case 1A 36-year-old previously healthy man was transferred to the University of Iowa Hospitals shortly after the onset of right-sided weakness and the inability to talk. He did not have a history of cigarette smoking, alcohol consumption, or use of illicit drugs. There was no family history of stroke, heart disease, or other thrombotic disorders. On admission he had a global aphasia, right hemiparesis, right homonymous hemianopsia, and decreased sensory perception on the right. Carotid pulses were symmetrical, and there were no bruits. Cardiac examination was normal. He had no evidence of systemic embolization, peripheral edema, or deep-vein thrombosis.Computed tomography demonstrated an evolving ischemic infarct in the distribution of the left middle cerebral artery. A cerebral arteriogram demonstrated complete occlusion of the left middle cerebral artery (Figure 1). The proximal carotid and other intracranial vessels were normal. Laboratory studies included a normal complete blood count, normal concentrations of electrolytes, blood urea nitrogen, and creatinine, and normal serum chemistries. The total serum protein concentration was 4.1 (normal range 6-8) g/dl, and the serum albumin concentration was 2.4 (normal range 3.3-5) g/dl. Urinalysis revealed a high specific gravity of 1.027 and 3 + protein. Serum complement studies demonstrated a C 3 concentration of 76 (normal range 70-176) mg/dl and a decreased C 4 concentration of 9 (normal range 16-45) mg/dl. His evaluation also included a normal chest roentgenogram, a normal electrocardiogram, normal cardiac monitoring, and normal transthoracic, contrast, and transesophageal echocardiogTams. Venous Doppler study of the lower extremities was unremarkable. A 24-hour urine protein content was elevated at 11.4 (normal value <0.1) g. Prothrombin time, partial thromboplastin time, and thrombin time were normal. Fibrinogen concentration was increased to 701 (normal range 160-340) mg/dl. He had normal antithrombin-III, total protein-S, and protein-C concentrations. Plasminogen content was increased to 145% (normal range 90-110%). Free protein-S content was decreased to 55% (normal range 60-140%). Other studies included a nonreactive VDRL and negative assays for antinuclear antibodies, anticardiolipin antibodies, neutrophil cytoplasmic antibody, and cryoglobulins. Blood...

The general evaluation of the success of a regional mental health program was attempted through the use of the Goal Attainment Scale. There were 278 goal guides scored for 96 sample patients at periods of 6, 12, and 18 months after admission. The interrater reliability between pairs of raters at follow-up interviews was high (.87). The intraclass correlation for goal guides constructed by three independent goal setters was moderate (r=.71). The mean scores of the three raters, when compared to a consensus goal score, attained an intraclass coefficient of .91. Thus the goal-attainment scoring procedure was found to be reliable. However, no evidence could be discerned to support its validity as a measure of a patient's treatment outcome.

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We reviewed clinical features and outcomes of 16 patients (3 men and 13 women) aged 18–68 years, with nonseptic, nontraumatic superior sagittal sinus thrombosis (SSST). Most common risk factors were oral contraceptives, a postpartum state or malignancy. Two patients were noted to have a ‘lupus anticoagulant’; 1 of these had prior venous thrombosis in the legs and recurrent spontaneous abortions but no antiphospholipid antibodies. Five patients had ;poor outcomes, including 4 deaths. Of the 11 patients with good outcomes, 9 had no residual deficits. Intracranial hemorrhage was noted on initial CT in 3 patients. One had hemorrhagic transformation of a bland cerebral infarction without use of anticoagulants, as did 1 after receiving only 1,600 IU of intravenous heparin. Of the 11 patients who had a good outcome, 5 received full-dose intravenous heparin. Of the 5 patients who had a poor outcome, none received full-dose heparin due to the presence of either a large infarction or hemorrhage. Due to its infrequent occurrence and heterogenous nature, recommendations regarding heparin therapy for patients with nonseptic SSST should be individualized.