The Preclinical Safety Evaluation of Human Monoclonal Antibody against Cytomegalovirus

The human monoclonal antibody against cytomegalovinis (Mab C23)was examined pharmacokinetically and toxicologically as partof the preclinical studies prior to approval for human use.Rats given repeated intravenous administrations of Mab C23 producedno antibodies against Mab C23 and maintained a blood Mab C23level in a dose-dependent manner. However, pregnant rabbitsproduced antibodies against Mab C23. The half-life of Mab C23in plasma was 15.9 days in rats, which was similar to that ofnormal human serum -globulin (NHSG). Neither behavioral effectsnor circulatory disturbance was found in mice, rats, and dogseven after a single intravenous injection of 100 or 200 mg/kg,which corresponds to 50 or 100 times the intended clinical dosage.The repeated doses of 2, 10, or 20 mg/kg of Mab C23 on six occasionswith 1- or 2-week intervals elicited a transient decrease inleukocyte counts in rats given 10 or 20 mg/kg, but no adverseeffects in cynomolgus monkeys. Mab C23 did not cause any reproductiveor developmental toxicity when administered to rats and rabbitsat dose levels of 20 mg/kg or less. However, pregnant animalsshowed lower plasma levels of Mab C23 than non-pregnant animals.The chromosomal aberration test disclosed no clastogenicityin human lymphocytes. An immunostaining for Mab C23 revealedno localizations in several tissues of cynomolgus monkeys givenintravenous doses of Mab C23. The preclinical safety evaluationin animals other than rabbits, which produced no antibodiesagainst Mab C23, showed that the behavior of Mab C23 is pharmacokineticallysimilar to that of NHSG and is as safe as NHSG, which has longbeen used as a biological agent. However, because there wasa difference in blood levels of Mab C23 between pregnant andnonpregnant animals, its clinical administration to pregnantpatients should differ from that to non-pregnant patients.     

Personality differences in the Munich Personality Test between patients with major depression and panic disorder

This study attempted to determine whether patients with major depression and panic disorder could be differentiated by personality features, measured by the Munich Personality Test (MPT). One of the six MPT personality dimensions, `rigidity', was developed in relation to the `melancholic type of personality', which may be a specific personality feature of depressive subjects. We therefore hypothesized that the MPT might be sensitive to possible personality differences between patients with major depression and panic disorder. Sixty-six patients with major depression and 27 patients with panic disorder, taken from consecutive intakes at an outpatient unit, were compared in terms of six personality dimensions of the MPT. The results demonstrated that rigidity could significantly differentiate the two patient groups, even after the possible confounding effects on the personality assessments were statistically partialled out. The MPT was suggested to be powerful for describing distinctive personality features of depressive subjects from anxiety subjects.     

Perspectives on phantom boarder symptom

Phantom boarder symptom (PBS) is a hallucinatory and delusional syndrome that tends to occur in the elderly, in which the patient imagines that someone uninvited is living in their home. This article provides an overview of the historical background that has led to the current focus on PBS as a single symptom, from its classification as late paraphrenia to its being recognized as a type of misidentification, and discusses classification problems and PBS subclassifications. In addition, the results of our own investigation of PBS, which focused on PBS in senile dementia, support the findings of previous studies, such as the absence of a relationship between dementia severity and the occurrence of delusion. The discussion therefore focuses on the psychosocial factors that serve as the mechanism of PBS onset, and directions and possibilities for therapy are suggested.     

Haemophagocytic syndrome associated with Epstein-Barr virus infection and promoted by tuberculosis reactivation in a patient undergoing chronic haemodialysis

SUMMARY: A 73-year-old man who had been undergoing chronic haemodialysis (CHD) for 3 years developed haemophagocytic syndrome (HPS) that might have been triggered by Epstein-Barr virus (EBV) infection. the patient finally died of miliary tuberculosis (TB) reactivation that promoted the progression of HPS. Immunological abnormalities in patients undergoing CHD may be notable. the early diagnosis of TB reactivation may be important for reducing the mortality in cases of HPS, as a high incidence of TB is encountered in patients undergoing CHD. In contrast, the simultaneous occurrence of an EBER-positive hybridization signal with T cell-specific immunolabelling of CD45RO cells was well detected in the spleen and lymph nodes, and interferon gamma was elevated in the serum. These findings coincide with the reported preferential expansion of T cells rather than B cells in EBV infection, and support the hypothesis that systemic hypercytokinaemia caused by the proliferation of EBV-infected T cells may play a crucial role in the development of HPS.     

Magnetic resonance imaging study of the brain in aged volunteers: T2 high intensity lesions and higher order cortical function

Abstract The aims of the present study were to clarify the findings of magnetic resonance imaging (MRI) in the aging brain, and to relate the MRI findings to higher order cortical function. A total of 118 healthy aged volunteers (41 men, 77 women) underwent cranial MRI electroencephalography (EEG), Benton visual retention test (BVRT) and interview. The subjects had no past history or clinical evidence of cerebrovascular disorder, head trauma or dementia and were living at home without any difficulty. The majority of the subjects have participated in this series of studies since 1982. Using a 1.5 T superconductive MR instrument, T1-weighted, proton density and T2-weighted images were obtained. The MRI data were rated visually by regarding 12 items according to fixed criteria. T2 high signal intensity (T2HSI) lesions were found in 69.5% of subjects, the prevalence of which increased with age. T2HSI lesions were most frequently found in the basal ganglia (61.9%), followed by the thalamus (39.0%), parietal lobe (37.0%), temporal lobe (12.7%) and pons (8.5%). Among these lesions, lacunar infarction showed low signal intensity in T1-weighted images and was found in 24.6% of subjects, the prevalence also increasing with age. These findings, including brain atrophy determined according to similar criteria, were correlated closely with the subjects' age. The results of BVRT showed a close relation with T2HSI, suggesting that T2HSI may influence cognitive function. When the subjects were classified according to the presence of T2HSI, lacunar infarction and EEG abnormalities, brain atrophy was significantly milder in a group of subjects with T2HSI(-), lacunar infarction(-) and normal EEG than in the other groups. This suggests that changes seemingly representing physiological aging may be promoted by another pathological which also exerts influences on higher order cerebral function.     

Defective Calcium-Dependent Signal Transduction in T Lymphocytes of Ataxia-Telangiectasia

T-cell functions of two patients with ataxia-telangiectasia were investigated. Patients with ataxia-telangiectasia had reduced percentages of circulating CD3⁺ cells and CD4⁺ cells, although neither patient had a reduced percentage of circulating CD8⁺ cells. The proliferative responses and interleukin-2 production of peripheral blood mononuclear cells to T-cell mitogens were reduced in the patients. The intracellular calcium concentration in T cells or CD4⁺ cells from both patients was only slightly increased after phytohaemagglutinin stimulation. Moreover, the concentration after OKT3 stimulation was not or only slightly increased in T cells or CD4⁺ cells from both patients. Our results suggest that the functional defect of T cells is caused by defective Ca²⁺-dependent signal transduction through the CD3 complex of the surface in T cells of ataxia-telangiectasia.