The CLDN5 locus may be involved in the vulnerability to schizophrenia.

The present study was designed to detect three single nucleotide polymorphisms (SNPs) located on 22q11 that was thought as being of particularly importance for genetic research into schizophrenia. We recruited a total of 176 Chinese family trios of Han descent, consisting of mothers, fathers and affected offspring with schizophrenia for the genetic analysis. The transmission disequilibrium test (TDT) showed that of three SNPs, rs10314 in the 3'-untranslated region of the CLDN5 locus was associated with schizophrenia (chi(2) = 4.75, P = 0.029). The other two SNPs, rs1548359 present in the CDC45L locus centromeric of rs10314 and rs739371 in the 5'-flanking region of the CLDN5 locus, did not show such an association. The global chi-square (chi(2)) test showed that the 3-SNP haplotype system was not associated with schizophrenia although the 1-df test for individual haplotypes showed that the rs1548359(C)-rs10314(G)-rs739371(C) haplotype was excessively non-transmitted (chi(2) = 5.32, P = 0.02). Because the claudin proteins are a major component for barrier-forming tight junctions that could play a crucial role in response to changing natural, physiological and pathological conditions, the CLDN5 association with schizophrenia may be an important clue leading to look into a meeting point of genetic and environmental factors.     

Evidence of melanogenesis in porcine retinal pigment epithelial cells in vitro

Several weeks after porcine retinal pigment epithelial (RPE) cell cultures attain confluence, macroscopically visible brown foci appear. The cuboidal cells that form the foci contain numerous phase dark granules that do not exhibit the autofluorescence characteristic of lipofuscin. The data described here indicate that the granules are melanosomes. Electron microscopy revealed three types of electron-dense granules in these cells: simple spheres 0.3-0.5 microns in diameter, large spheres 1-2 microns in diameter, and lysosomal aggregations of the smaller spheres. The matrix of both spheres is composed of 40-nm microvesicles that were also found free in the cytoplasm and aggregated within vacuolar structures. Reversed-phase high-performance liquid chromatography of RPE cells and their media detected melanogens, i.e. intermediates of melanin biosynthesis, including several indole derivatives. The porcine RPE cultures therefore may be a useful system for studying melanogenic regulation.     

NADPH-Diaphorase-Positive Neurons in Primate Cerebral Cortex Colocalize with GABA and Calcium-Binding Proteins

Neurons in the monkey cerebral cortex containing nicotinamideadenine dinucleotide phosphate-diaphorase (NADPH-d) can he dividedinto two distinct types, both nonpyramidal. Type I neurons havea large soma (diameter 20–50 µm), a dense NADPH-dhistochemical reaction. and are distributed throughout the cortex,but mainly in the subcortical white matter, and are mostly aspiny.Type II cells have a small soma (< 20 µm) with lightNADPH-d reactivity and are distributed primarily in the supragranularlayers, particularly layers II and upper III. The numericaldensity of type II cells is much greater than that of type I.Type I neurons also stain for GABA and a few intracortical typeI cells contain calbindin. All type II cells found here arecolocalized with both GABA and calbindin. Neither type I nortype II cells are stained for parvalbumin. Together with previous observations that almost all corticalNADPH-d cells in various subprimates are like type I cells,we suggest that type II cells may form a group of NADPH-d-richneurons differentiated in higher mammalian cortex from a subpopulationof calbindin-containing GABAergic interneurons, and these nitricoxide-synthesizing cells may play a role in control of intracorticalneuronal activity characteristic of higher cerebral functionsin advanced mammals.     

Acute and chronic hemodynamic effects of xamoterol in mild to moderate congestive heart failure.

Xamoterol, a new beta 1 partial agonist, has the potential to modulate cardiac response to variations in sympathetic tone in patients with heart failure. Its properties should result in beta-receptor stimulatory effects at low levels of sympathetic tone and beta-receptor protective effects at higher levels of sympathetic tone. The acute effects of intravenous (i.v.) xamoterol on hemodynamics at rest and during exercise were studied in 30 patients with mild to moderate heart failure (13 patients in New York Heart Association class II; 17 in class III) due to ischemic (n = 24) or cardiomyopathic (n = 6) heart disease. Cardiac index, stroke volume and stroke work index at rest were significantly improved after i.v. administration of xamoterol and consistent with net agonist effects. During exercise, heart rate and double product were significantly reduced (net antagonist effects), but with preservation of the expected increases in cardiac index and systolic blood pressure. These hemodynamic findings confirm the ability of xamoterol to modulate cardiac response to variations in sympathetic tone. Tachyphylaxis and arrhythmogenicity limit the chronic use of drugs with full beta-agonist properties as positive inotropes in heart failure. The patients were therefore entered into a 6-month double-blind, placebo-controlled, crossover study of chronic oral xamoterol therapy, 200 mg twice daily, and the hemodynamic responses to i.v. xamoterol were repeated at the end of the trial. No impairment in either resting or exercise effects was observed, indicative of a maintained response and absence of tachyphylaxis after chronic therapy. Furthermore, 24-hour ambulatory electrocardiographic monitoring showed no change in ventricular arrhythmias during oral treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Principles for managing penetrating craniocerebral injuries caused by firearm missiles

Penetrating craniocerebral firearm injuries remain one of the most lethal causes of all trauma and are common both in war or peace time. Data were reviewed for 4140 severely head-injured patients (Glasgow Coma Scale (GCS) scores 3-8) treated at Xi-Jing Hospital between 1973 and 1993; 51 of these patients had acute penetrating craniocerebral injuries caused by firearm missiles. These patients consisted of 46 males (90.2%) and 5 females (9.8%) ranging in age from 3 months to 48 years (median 22.4 years). The lesion types included 2 tangential wounds, 37 tubular wounds and 12 through-and-through wounds. All cases were urgent with the patients in severe and unstable states. After emergency treatment and operation, 5 cases died (9.8%). Follow up studies at three months showed that 23 cases (45.1%) had made a good recovery. Moderate disability, severe disability and vegetative states in this series were 29.4%, 13.7% and 2.0% respectively. Long term follow up studies indicated that 32 were able to resume their occupation. The principles for managing penetrating craniocerebral firearm injuries and suggestions for operation are discussed.     

Reconstruction of the anterior face of the base of the skull using coral grafts

Following experimental investigations on animals, small coral grafts have been utilized on patients since 1985 to fill in burr holes (42 patients). This first clinical experimental step has been satisfactory. Therefore, blocks of corals have since then been used as bone graft substitutes for anterior skull basis reconstruction (12 patients). Cheap and easily sterilized, coral implants have the advantage of being inert (99% of calcium carbonate), biodegradable and well reossified. They shorten surgical procedures by avoiding the use of iliac and/or costal grafts. No infectious complications have been noted.     

Influence of pancreas transplantation on cardiorespiratory reflexes, nerve conduction, and mortality in diabetes mellitus

Cardiorespiratory reflexes (CRR) were studied by measuring heart-rate variation during 6 breaths/min respiration and a Valsalva maneuver in 232 insulin-dependent diabetic subjects. Abnormalities were found in 175 patients. During a 7-yr follow-up, 41 (23.4%) patients with abnormal and 2 (3.5%) with normal CRR tests died. The mortality rates of diabetic patients with abnormal autonomic function tests were 17% at 2.5 yr, 33% at 5 yr, and 40% at 7 yr, significantly higher (P less than 0.002) than in patients with normal tests (rates of 4.6, 4.6, and 13.8% at the respective intervals). Nerve conduction studies (NCS) were indicative of somatic neuropathy in 148 of 205 patients. Mortality rates were higher in patients with abnormal NCS than in those with normal results (P less than 0.025). Among patients with abnormal autonomic function, patients with a functioning pancreas transplantation (PTx) had better survival rates than patients with a failed PTx (P less than 0.005) and, on long-term follow-up, better rates than patients without PTx. Similar results were found comparing the same group of patients who had abnormal NCS.     

Effects of an anti-interleuktn-6 (IL-6) murine monoclonal antibody in a patient with acute monoblastic leukemia

Because IL-6 has been involved in the pathogenesis of acute monoblastic leukemia, we investigated thein vitro anti-proliferative effect and thein vivo anti-tumoral effect of an anti-IL-6 murine monoclonal antibody (mAb) in a patient with MSB type acute leukemia. In the current study, we clearly show the IL-6 dependence of monoblastic cell viability and proliferationin vitro in short-term cultures of malignant cells and the clinical activity of the anti-IL-6 murine mAb. The complete neutralization of IL-6in vivo was associated with a transient but complete disappearance of malignant monoblastic cells in the peripheral blood, with improvement or even normalization of several other biological parameters of disease activity, No immunization against the anti-IL-6 murine mAb was observed.