Comparative expression of the psoriasin (S100A7) and S100C genes in breast carcinoma and co-localization to human chromosome 1q21-q22

Using differential screening of a breast cancer cDNA library, we isolated a cDNA encoding the psoriasin (S100A7) protein, previously identified in psoriatic epidermis. In the present study, we demonstrate that the psoriasin gene is expressed in breast cancer cell lines and in cancer cells of some breast carcinomas but not in any non-cancerous tissues examined, except skin. Another S100 gene, S100C, which we co-localized with the psoriasin gene to human chromosome Iq21-q22, was found to be expressed in most tissues and cell lines evaluated. These findings add support to the concept that the S100 genes clustered in human chromosome Iq21-q22 are individually controlled and that some of them may be involved in the regulation of cell transformation and/or differentiation.     

Effect of age of onset of temporal lobe epilepsy on the severity and the nature of preoperative memory deficits

The nature and severity of pre-operative memory deficits observed in unilateral temporal lobe epilepsy depend upon a number of variables. Among these variables, age of seizure onset seems to be important. The age at which the lesion is sustained could modify the normal functional organization of the brain. Many studies have examined the effect of age of onset on the severity of memory deficits but have seldom focused on the nature of such deficits (verbal/nonverbal) as a function of epileptic focus laterality. This study investigates the effect of age of onset on the nature and severity of memory impairments. Fifty-six epileptics with unilateral temporal lobe epilepsy and 20 normal subjects were administered a neuropsychological evaluation. Four groups of patients were constituted: left or right temporal lobe epilepsy with early (0-5 years) or late (10 years and over) age of seizure onset. The early group showed major verbal and nonverbal memory deficits. The late group presented minor specific deficits: essentially verbal deficits with left temporal lobe seizures and nonverbal deficits with right temporal lobe seizures. These results may be interpreted in the framework of ontogenesis theories of hemispheric specialization.     

Cannabis use correlates with schizotypal personality traits in healthy students

The literature suggests that cannabis use and schizotypal traits both constitute risk factors for the later development of schizophrenia. However, their interrelationships remain to be evaluated. The present study examined the association between cannabis use and schizotypal traits in 232 healthy students who ranged in age from 18 to 25 years. All the students had completed the Schizotypal Personality Questionnaire and four of the Chapman Psychosis Proneness Scales: the Magical Ideation Scale; the Perceptual Aberration Scale; the Revised Physical Anhedonia Scale; and the Revised Social Anhedonia Scale. Subjects were divided into three groups according to cannabis use typology: those who had never used cannabis, those who were past or occasional users, and those who were regular users. Higher scores on the Schizotypal Personality Questionnaire and the Magical Ideation Scale characterized the regular and past or occasional users compared with those who had never used cannabis. The co-occurrence of cannabis use and schizotypal traits appeared to be independent of anxiety and depression dimensions. These data suggest that cannabis use and schizotypal traits have to be jointly considered in further longitudinal studies of schizophrenia risk factors.     

Laboratory diagnosis of congenital von Willebrand disease

Von Willebrand disease (vWD) is caused by quantitative or qualitative defects, or both, of the von Willebrand factor (vWF), a multimeric high-molecular glycoprotein (GP). Typically, it affects the primary hemostatic system, which is reflected by a mucocutaneous bleeding tendency simulating a platelet function defect. The vWF promotes its function in two ways: (1) by supporting platelet adhesion to the injured vessel wall under conditions of high shear forces and (2) by its carrier function for factor VIIIc (FVIIIc) in plasma. Because of the complexity of the disease, diagnosis of vWD is one of the most challenging of any coagulation disorder. The stepwise diagnosis of vWD includes patients and family history, screening procedures (bleeding time [BT], filter tests, platelet counts, activated partial thromboplastin time [aPTT]), confirmatory tests (vWF antigen [vWF:Ag], vWF ristocetin cofactor activity [vWF:RCo], vWF collagen-binding [vWF:CB] assay, ristocetin-induced platelet aggregation [RIPA], FVIIIc) and tests for final classification (multimeric analysis, FVIII binding capacity of vWF [vWF:FVIIIB], platelet vWF). In 1999, we classified 303 patients with congenital vWD as type 1 (n = 122), type 2 (n = 171), and type 3 (n = 10). Type 2 was further subdivided into type 2A (n = 126), type 2B (n = 17), type 2M (n = 22), and type 2N (n = 6). Type 2A showed a remarkable heterogeneity, with only 27.8% (n = 36) of the "classic" IIA pattern. The other high-frequency patterns were type IB (25.4% n = 32) and type IIE/F/H-like structural abnormalities (28.6% n = 36). The spectrum was completed with samples from patients with types 2D, 2C, 2C Miami, smeary structures, and other rare subtypes (together 18.9% n = 23).     

Comparison between macaques' and humans' kinematics of prehension: the role of morphological differences and control mechanisms

Reaching and grasping has been widely studied in both macaques and humans, mainly with the aim of finding similar patterns of behavior in the two species. Little attention has yet been given to how morphological and behavioral differences between the two species might affect the kinematics of the movement. In this study, we present a careful analysis of the similarities and differences between humans' and macaques' prehension movements and discuss these with respect to both the control system and the biomechanics of the arm. Five humans and five macaques performed the same task, namely grasping small feeding objects using a precision grip. Macaques were observed in unconstrained conditions, free to adjust their body posture. The behavioral protocol for macaques revealed a postural preference for sitting and keeping the elbow slightly flexed when applying a precision grip. In agreement with the literature, kinematics revealed general features of movement common to both humans and macaques. However, within a similar timeframe, macaques produced steeper and wider excursion of the elbow and of the wrist, smaller abduction of the shoulder joint and larger displacement of the torso than humans did. The three-joint limb revealed stronger irregularities for the macaques. We hypothesize that the larger kinematic irregularities and the specific elbow--shoulder posture in macaques result in part from an effort of the control system to compensate for different biomechanical constraints, namely for limited shoulder-joint excursion, in order to achieve a similar range of comfort of motion. Finally, we briefly consider the influence of primitive neural circuits responsible for arm motion during locomotion and speculated on their influence on the control of reaching in macaques.     

Contribution of solid-state properties to the aqueous solubility of drugs.

This study investigates the influence of the solid-state properties melting point (T(m)), enthalpy of melting (DeltaH(m)) and entropy of melting (DeltaS(m)) of a drug on its intrinsic solubility (S(0)). For this purpose, 26 chemically and structurally diverse drugs covering the oral drug space were selected and the S(0), T(m), DeltaH(m) and DeltaS(m) were determined experimentally. The influence of T(m), DeltaH(m) and DeltaS(m) on S(0) was studied using regression analysis. The overall improvement of the predictions were 0.3 log units, however, five compounds (astemizole, glyburide, fenbufen, gliclazide and griseofulvin) were improved by more than one log unit. T(m) and DeltaH(m) had a larger effect than DeltaS(m) on the solubility predictions. The well-known general solubility equation (GSE) and the Dannenfelser semi-empirical equation for the calculation of DeltaS(m) were evaluated using our data set. While predictions of drug solubility obtained using the GSE were acceptable, the use of the experimental DeltaS(m) values instead of the constant 56.5 J mol(-1)K(-1) improved the accuracy of the prediction. The Dannenfelser equation underestimated the DeltaS(m) for most compounds with on average 15 J mol(-1)K(-1). Our results show that solid-state properties should be considered for improved performance of future models for prediction of drug solubility. In addition our study provides accurate experimental data on intrinsic solubility for 26 compounds, supplying a useful external data set for validation of drug solubility models.     

Von Willebrand Disease type 2M "Vicenza" in Italian and German patients: identification of the first candidate mutation (G3864A; R1205H) in 8 families

Von Willebrand disease type 2M "Vicenza" (VWD 2M V) is characterised by autosomal dominant inheritance, low von Willebrand factor (VWF) and the presence of "supranormal" multimers in plasma. This specific phenotype has been described in Italian and recently also in German patients. The molecular defect is linked to the VWF gene. However, no specific mutations have been identified until now. We analysed the complete coding region and adjacent intron sequences of the VWF gene in Italian families in comparison to German families with VWD 2M V by a PCR-based mutation screening, combined with SSC- and heteroduplex-analysis of exons 2 through 52, followed by direct sequencing. We identified the first heterozygous candidate mutation (G3864A; R1205H) in all affected members of the 7 Italian families and in 1 German patient but not in the unaffected family members nor on 100 chromosomes of normal subjects, suggesting a causal relationship between the mutation and the phenotype. Haplotype identity, with minor deviations in one Italian family, suggests a common but not very recent genetic origin of R1205H.