Murine retroviral vector that induces long-term expression of HIV-1 envelope protein

A retroviral vector was constructed that induces long-term expression of human immunodeficiency virus type 1 (HIV-1) rev, vpu and env genes. The vector contains the neo gene and a cytomegalovirus (CMV) immediate early promoter followed by HIV-1 sequence. When HeLa cells were infected with viral stocks derived from this vector, about 25% of the resulting G418-resistant clones expressed HIV-1 envelope protein (Env), easily detectable by Western blot analysis, metabolic labelling, and syncytium formation after co-cultivation with HeLa-CD4 cells. In most cases the level of Env expression was higher than in a T cell line (H9) chronically infected with HIV-1. Env-expressing HeLa cell lines also expressed Rev, detected by transfection with a Rev-dependent CAT gene construct, and Vpu, detected by immunoprecipitation with a Vpu-specific antiserum. The 75% of G418-resistant HeLa cell lines that did not express Env were found to contain proviruses that had undergone deletion of env sequences corresponding to a known intron; presumably these cell lines arose as a result of infection with virions derived from spliced RNAs. This vector should be useful for studying non-transient effects of HIV Env, Rev and Vpu in tissue culture, and for the production of Env- and/or Rev-expressing cell lines.     

Primary aortic mural thrombus: presentation and treatment

Schizophrenic patients are extremely heavy tobacco smokers. However, a lower incidence of lung cancer in schizophrenic patients has been observed in comparison to other heavy smokers. Nicotine increases the proliferation of pulmonary neuroendocrine tissue, causing the release of a bombesin-like peptide. Thus, bombesin-like peptide levels in urine may be an indicator of precancerous, cigarette-induced lung damage. Bombesin-like peptide levels of 10 schizophrenic smokers and 11 schizophrenic nonsmokers were compared to those of nonschizophrenic subjects matched for age and pack-years of smoking. The nonschizophrenic smokers showed the expected increase in urinary bombesin-like peptide levels, as compared to nonschizophrenic nonsmokers. Schizophrenic patients had lower bombesin-like peptide levels independent of smoking effects. The mechanism of the difference in bombesin-like peptide levels between schizophrenic patients and nonschizophrenic subjects is unknown, but one possibility involves alteration in the alpha 7-nicotinic acetylcholine receptor, which mediates the growth of some neuroendocrine cell lines in vitro.     

Mode of chemotherapy does not affect complications with an implantable venous access device

BACKGROUND: Few reports have been made regarding the long term safety of implantable venous access devices used for the delivery of chemotherapeutic agents. The authors' goals were to determine the frequency of complications in patients receiving chemotherapy with these devices; to determine whether complications were associated with the mode of chemotherapy delivery (push/bolus or infusional regimens); and to evaluate the influence of other risk factors, including home-based versus hospital-based administration. METHODS: A total of 152 oncology patients at the John L. McClellan Memorial Veterans Administration Medical Center in Little Rock, Arkansas (ages 26-81 years; mean age, 62 years), who underwent surgical placement of an Infus-a-Port (Strato, Inc., Beverly, MA) between May 1, 1992 and May 31, 1994, were evaluated retrospectively for postplacement device complications, such as infection, thrombosis, and mechanical failure. RESULTS: Twenty-seven patients experienced 1 complication each: 17 episodes of device-related sepsis, cellulitis, or fever of unknown origin; 8 episodes of thrombosis or catheter occlusion; 1 episode of drug extravasation; and 1 mechanical failure. Patient age, frequency of port accession, mode of chemotherapy delivery, tumor type, and neutropenia were evaluated as risk factors, but none was statistically significant. Complications were more frequent during the first 90 days after implantation, but they continued to occur throughout the observation period. CONCLUSIONS: Complications attributable to an implantable venous access device were infrequent in this patient population. No differences in complications for patients receiving home-based versus hospital-based chemotherapy administration were noted, opening the possibility of significant time and cost savings with home treatment.     

Neither L-arginine nor L-NAME affects neurological outcome after global ischemia in cats

BACKGROUND AND PURPOSE: We attempted to determine whether N-nitro-L-arginine methyl ester (L-NAME) would improve neurological outcome and whether L-arginine (L-ARG) would worsen neurological outcome after transient global ischemia. METHODS: Halothane-anesthetized cats (n = 6 for each group) were treated with intravenous saline, L-NAME (5 mg/kg or 10 mg/kg), or L-arginine (300 mg/kg) 30 minutes before 10 minutes of ischemia (temporary ligation of the left subclavian and brachiocephalic arteries with hemorrhagic hypotension to 50 mm Hg). At 30 minutes of reperfusion, cats in the L-ARG group were administered an additional 300 mg/kg dose of intravenous L-arginine. RESULTS: Time (mean +/- SE) to isoelectric electroencephalography was similar among groups (saline, 26 +/- 11 seconds; L-NAME-5, 15 +/- 4 seconds; L-NAME-10, 36 +/- 27 seconds; and L-ARG, 22 +/- 7 seconds). At 72 hours, reperfusion pathological injury was severe and neurological deficit score (mean, range) was similar among groups (saline, 38[11 to 70]; L-NAME-5, 52 [40 to 73]; L-NAME-10, 47 [23 to 70]; and L-ARG, 40 [0 to 79]). CONCLUSIONS: Nitric oxide is not important in the mechanism of brain injury after global ischemia in cats.     

Use of hypertonic (3%) saline/acetate infusion in the treatment of cerebral edema: Effect on intracranial pressure and lateral displacement of the brain

OBJECTIVE: To determine the effect of continuous hypertonic (3%) saline/acetate infusion on intracranial pressure (ICP) and lateral displacement of the brain in patients with cerebral edema. DESIGN: Retrospective chart review. SETTINGS: Neurocritical care unit of a university hospital. PATIENTS: Twenty-seven consecutive patients with cerebral edema (30 episodes), including patients with head trauma (n = 8), postoperative edema (n = 5), nontraumatic intracranial hemorrhage (n = 8), and cerebral infarction (n = 6). INTERVENTION: Intravenous infusion of 3% saline/acetate to increase serum sodium concentrations to 145 to 155 mmol/L. MEASUREMENTS AND MAIN RESULTS: A reduction in mean ICP within the first 12 hrs correlating with an increase in the serum sodium concentration was observed in patients with head trauma (r2 = .91, p = .03), and postoperative edema (r2 = .82, p = .06), but not in patients with nontraumatic intracranial hemorrhage or cerebral infarction. In patients with head trauma, the beneficial effect of hypertonic saline on ICP was short-lasting, and after 72 hrs of infusion, four patients required intravenous pentobarbital due to poor ICP control. Among the 21 patients who had a repeat computed tomographic scan within 72 hrs of initiating hypertonic saline, lateral displacement of the brain was reduced in patients with head trauma (2.8 +/- 1.4 to 1.1 +/- 0.9 [SEM]) and in patients with postoperative edema (3.1 +/- 1.6 to 1.1 +/- 0.7). This effect was not observed in patients with nontraumatic intracranial bleeding or cerebral infarction. The treatment was terminated in three patients due to the development of pulmonary edema, and was terminated in another three patients due to development of diabetes insipidus. CONCLUSIONS: Hypertonic saline administration as a 3% infusion appears to be a promising therapy for cerebral edema in patients with head trauma or postoperative edema. Further studies are required to determine the optimal duration of benefit and the specific patient population that is most likely to benefit from this treatment.     

Lysosomal targeting of P-selectin is mediated by a novel sequence within its cytoplasmic tail

Signals controlling the intracellular targeting of many membrane proteins are present as short sequences within their cytoplasmic domains. P-selectin is a type I membrane protein receptor for leukocytes, acting during the inflammation response. Heterologous expression experiments have demonstrated that its 35-residue cytoplasmic tail contains signals for targeting to synaptic-like microvesicles, dense-cored granules, and lysosomes. We have examined the lysosomal targeting information present within the cytoplasmic tail by site-directed mutagenesis of horseradish peroxidase-P-selectin chimeras followed by transient transfection in H.Ep.2 cells. Assaying lysosomal targeting by subcellular fractionation as well as intracellular proteolysis, we have discovered a novel lysosomal targeting signal, KCPL, located within the C1 domain of the cytoplasmic tail. Alanine substitution of this tetrapeptide reduced lysosomal targeting to the level of a tailless horseradish peroxidase-P-selectin chimera, which was previously found to be deficient in both internalization and delivery to lysosomes. A proline residue within this lysosomal targeting signal makes a major contribution to the efficiency of lysosomal targeting. A diaminobenzidine density shift procedure established that chimeras with an inactivated KCPL sequence are present within transferrin-positive compartments. Such a mutant also displays an increased level of expression at the plasma membrane. Our results indicate that the sequence KCPL within the cytoplasmic tail of P-selectin is a structural element that mediates sorting from endosomes to lysosomes.     

Symptomatic recurrent carotid stenosis and aneurysmal degeneration after endarterectomy

BACKGROUND: Aneurysmal degeneration of a carotid reconstruction was not recognized until the patient, who was known to have recurrent carotid artery stenosis, had a thromboembolic stroke. This sequelae of carotid endarterectomy is a serious complication, associated with a high morbidity and mortality rate. This review was conducted to establish the risk of transient ischemic attack and stroke for patients found to have recurrent carotid stenosis associated with aneurysmal degeneration of the carotid artery after endarterectomy. METHODS: A case is reported, and 100 literature references of aneurysmal degeneration of the carotid artery after endarterectomy were reviewed. RESULTS: False aneurysm from anastomotic disruption was the most common presentation identified in the cases reviewed. Nineteen of the patients had a significant neurologic event; however, three (50%) of six patients with aneurysm and recurrent carotid artery stenosis had a transient ischemic attack or stroke. CONCLUSIONS: The incidence of neurologic symptoms is markedly increased when recurrent carotid artery stenosis is associated with carotid aneurysm. During postoperative surveillance after endarterectomy, the identification of recurrent carotid artery stenosis requires evaluation for aneurysmal degeneration of the carotid artery with duplex scanning. These patients are at significant risk for transient ischemic attack and stroke. This rare complication merits operative repair.     

合成二氧化氯的催化剂和方法及该催化剂的制备

使用一种失活速率降低的催化剂用亚氯酸钠的水溶液合成二氧化氮。催化剂最好为钯,钯与其它钯系金属的混合物（如Ｐｂ＋Ｐｔ）或者是钯与第１副族金属的混合物（Ｐｂ＋Ａｕ）,所用的载体为可用第１主族金属的硕酸盐如（Ｋ２ＣＯ３）、第２主族金属的碳酸盐（如ＣａＣＯ３）或者是可转化成ＭｇＯ的镁盐改性的物质,载体还可以是第１主族金属的碳酸盐（如Ｋ２ＣＯ３）或者是可转化成ＭｇＯ的镁盐改性的物质,载体还可以是第１主族金属     

Genomic organization, fine-mapping, and expression of the human islet-brain 1 (IB1)/c-Jun-amino-terminal kinase interacting protein-1 (JIP-1) gene

Islet-brain 1 (IB1), a regulator of the pancreatic beta-cell function in the rat, is homologous to JIP-1, a murine inhibitor of c-Jun amino-terminal kinase (JNK). Whether IB1 and JIP-1 are present in humans was not known. We report the sequence of the 2133-bp human IB1 cDNA, the expression, structure, and fine-mapping of the human IB1 gene, and the characterization of an IB1 pseudogene. Human IB1 is 94% identical to rat IB1. The tissue-specific expression of IB1 in human is similar to that observed in rodent. The IB1 gene contains 12 exons and maps to chromosome 11 (11p11.2-p12), a region that is deleted in DEFECT-11 syndrome. Apart from an IB1 pseudogene on chromosome 17 (17q21), no additional IB1-related gene was found in the human genome. Our data indicate that the sequence and expression pattern of IB1 are highly conserved between rodent and human and provide the necessary tools to investigate whether IB1 is involved in human diseases.