Failure of dominant left-hemispheric activation to right-ear stimulation in schizophrenia

Schizophrenia is associated with an absence of the lateralizations that typify the human brain. Previous evidence emphasized structural changes, particularly reduced asymmetry in extension and surface of the planum temporale, although gross structural deviations occur only in a minority of patients. The present study describes an absence of lateralization on a robust functional measure that characterized schizophrenia patients: healthy subjects but not schizophrenics displayed a contralateral left-hemispheric dominance of the auditory evoked magnetic field to right-ear auditory stimulation. Absence of contralateral dominance in response to auditory stimuli among schizophrenia patients may indicate a failure to establish unequivocal left-hemispheric dominance of the phonological loop as hypothesized by Crow.     

The Effect of Correlation between Price and Quality on Consumer Choice

According to the price-expectancy model of consumer choice, consumers evaluate products by comparing the actual price with a reference or expected price determined from (a) product's quality and (b) the price-quality correlation of the product category. Choices between hypothetical products of beer are used to test the model against a model without a reference price. Consistent with the price-expectancy model, product preferences varied with the subjective correlation between price and quality: the relative preference for higher priced/higher quality products over lower priced/lower quality products increased as the subjective correlation increased. For some pairs, the correlation between price and quality created a preference reversal across contexts: the higher priced/higher quality product was chosen over the lower priced/lower quality product in the higher correlational context, but the lower priced/lower quality product was chosen over the higher priced/higher quality product in the lower correlational context. An additional study provided evidence that the price-quality correlation affects reference price, rather than reference quality, formation. Copyright 1998 Academic Press.     

Neurobehavioral deficits in mice lacking the erythrocyte membrane cytoskeletal protein 4.1

The erythrocyte membrane cytoskeletal protein 4.1 (4.1R) is a structural protein that confers stability and flexibility to erythrocytes via interactions with the cytoskeletal proteins spectrin and F-actin and with the band 3 and glycophorin C membrane proteins. Mutations in 4.1R can cause hereditary elliptocytosis, a disease characterized by a loss of the normal discoid morphology of erythrocytes, resulting in hemolytic anemia [1]. Different isoforms of the 4.1 protein have been identified in a wide variety of nonerythroid tissues by immunological methods [2-5]. The variation in molecular weight of these different 4.1 isoforms, which range from 30 to 210 kDa [6], has been attributed to complex alternative splicing of the 4.1R gene [7]. We recently identified two new 4.1 genes: one is generally expressed throughout the body (4. 1G) [8] and the other is expressed in central and peripheral neurons (4.1N) [9]. Here, we examined 4.1R expression by in situ hybridization analysis and found that 4.1R was selectively expressed in hematopoietic tissues and in specific neuronal populations. In the brain, high levels of 4.1R were discretely localized to granule cells in the cerebellum and dentate gyrus. We generated mice that lacked 4.1R expression; these mice had deficits in movement, coordination, balance and learning, in addition to the predicted hematological abnormalities. The neurobehavioral findings are consistent with the distribution of 4.1R in the brain, suggesting that 4.1R performs specific functions in the central nervous system.     

Stereotactic radiosurgery for patients with nonsmall cell lung carcinoma metastatic to the brain

BACKGROUND: A retrospective study of patients undergoing stereotactic radiosurgery for one to four brain metastases from nonsmall lung cell carcinoma (NSCLC) was performed to document outcomes and risks. METHODS: Seventy-seven patients underwent radiosurgery during a 7-year interval; 71 also underwent whole brain radiation therapy. Univariate and multivariate analyses were used to determine significant prognostic factors affecting survival. RESULTS: The overall median survival was 10 months after radiosurgery, and 15 months from the diagnosis of brain metastases. Five factors significantly affected survival: extent of systemic disease, presence of a neurologic deficit, size of the intracranial tumor, initial imaging appearance of intratumoral necrosis, and initial resection of the primary tumor of the chest. Median survival time was 26 months in a subgroup of patients with no extracranial metastases, no neurologic deficits, and a small tumor without necrosis. The authors evaluated 91 tumors with imaging. Local tumor control was achieved in 77 lesions (85%) and tumoral radiation necrosis developed in 4 lesions (4.4%). Nineteen new metastatic tumors developed during the observation interval. CONCLUSIONS: Stereotactic radiosurgery for NSCLC brain metastases is effective and is associated with few complications. The early detection of brain metastases and treatment with radiosurgery combined with radiation therapy provide the opportunity for extended high quality survival.     

Immunohistochemical localization of carboxypeptidases E and D in the human placenta and umbilical cord

Carboxypeptidase E (CPE) is highly concentrated in neuroendocrine tissues and is the only carboxypeptidase detected in mature secretory vesicles. Carboxypeptidase D (CPD), a carboxypeptidase with CPE-like activity, is widely distributed in tissues and is present in the trans-Golgi network. Previous work had shown that both CPE and CPD are expressed in the human placenta and that CPD is expressed at much higher levels than CPE. The present work provides evidence for the co-localization of CPE and CPD to basal plate extravillous trophoblasts and maternal uteroplacental vascular endothelial cells, chorionic villous endothelial cells, amnionic epithelial cells, and umbilical venous and arterial smooth muscle cells. Whereas the intensity of CPD immunostaining is similar in the placenta and umbilical cord, CPE staining in the placenta is much weaker than in the umbilical cord, suggesting that CPD plays a more important role in the processing of placental peptides. Immunoelectron microscopy of umbilical venous smooth muscle cells shows subcellular localization of both enzymes to the rough endoplasmic reticulum. In addition, CPE is present just subjacent to the cell membrane. The difference in cellular and subcellular localization between the two enzymes indicates that they perform distinct functions in the processing of placental peptides and proteins.     

Correlates of college student marijuana use: results of a US National Survey

Drug resistance is one of the problems severely limiting chemotherapy in cancer patients. Thus, it is very important to develop new drugs that are effective against drug-resistant tumour cells. The novel anti-tumour agent NK109 has been developed from benzo[c]phenanthridine derivatives by Nippon Kayaku (Tokyo, Japan). We have confirmed that NK109 shows anti-tumour effects against a number of human tumour cell lines by inhibiting DNA topoisomerase II activity through the stabilization of the cleavable complex. Further, its efficacy against several drug-resistant tumour cell lines was also shown. NK109 showed potent anti-tumour activity against doxorubicin-resistant human tumour cell lines that have a typical multidrug resistance phenotype caused by P-glycoprotein. NK109 was not pumped extracellularly by P-glycoprotein and, consequently, NK109 accumulated in resistant cells. Cisplatin-resistant human tumour cell lines, which demonstrated decreased cisplatin accumulation, were sensitive to NK109. NK109 non-cross-resistance was confirmed using xenografts of tumour cells that were resistant to cisplatin in SCID mice. Furthermore, etoposide-resistant cells, with decreased topoisomerase II activity, were markedly sensitive to NK109 when compared with their parent cells, suggesting the possibility that the cytotoxic mechanism of NK109 differs from that of etoposide. In conclusion, NK109 is a very promising new anti-tumour drug for clinical use, because the efficacy of NK109 is not susceptible to several known molecular alterations that are associated with drug resistance. A clinical study of this compound is now in progress in Japan.     

Direct measurement of steroid sulfate and glucuronide conjugates with high-performance liquid chromatography-mass spectrometry

Laser Doppler flowmetry (LDF) is a sensitive method for the measurement of microvascular blood flow in tissue. The method has been found useful for estimating skin, liver, or gastrointestinal blood flow. Whether it can be applied laparoscopically and whether it is able to measure the intraparenchymal blood flow of an intraabdominal organ is still unknown. In a pilot study, 6 pigs received a laparotomy for placement of a 19-gauge LDF needle probe into the renal parenchyma. Three different locations of the lower pole kidney were chosen for the blood flow measurement. The reliability of using the instrument to measure the renal tissue blood flow was assessed by comparison of the results of renal arterial blood flow obtained from a well-established methodology--ultrasonic Doppler flowmetry. Recordings were taken following (a) intravenous administration of 0.005 mg/kg norepinephrine, (b) manual compression of the suprarenal aorta, and (c) intravenous injection of a lethal dose of phenobarbital (50 mg/kg). Measurements of LDF were possible in all kidney units. The renal tissue perfusion detected by LDF correlated excellently with the renal arterial blood flow under different renal perfusion pressures. The feasibility of using LDF probe to measure the renal tissue perfusion in a laparoscopic model was then assessed in 15 pigs. Under pneumoperitoneum, the right kidneys were approached transperitoneally with the animal in the decubitus position. A total of three trocars were used. The peritoneum and Gerota's fascia were incised and the LDF needle probe was manipulated and inserted by an endoforceps into the renal tissue via a 5-mm trocar. The insertion of the LDF needle probe was technically feasible in all 15 kidney units, and the depth of insertion could be adjusted under direct vision. Baseline values for the renal cortical and renal medullary blood flow were 50.1 +/- 17.7 and 8.8 +/- 3.3 ml/min/100 g tissue, respectively. Spatial variations of the LDF measurements averaged 6%, and temporal variations over 15 min averaged 5%. Four additional hemodynamic parameters were simultaneously recorded, including left carotid artery blood flow, aortic blood pressure, inferior vena caval pressure, and intraabdominal pressure. It appears that systemic and renal hemodynamic parameters can be monitored reliably and continuously in the porcine model. This method allows further information concerning hemodynamic changes and safety of laparoscopy to be obtained.