Development and characterization of a monoclonal antibody to human embryonal carcinoma

A monoclonal anti-testicular carcinoma antibody was obtained via the somatic cell fusion technique by immunization of BALB/c mice with freshly prepared single cell suspension from a patient with testicular embryonal carcinoma with choriocarcinoma components. The hybridoma supernates were screened against the testicular carcinoma cells used in the immunization as well as normal mononuclear white blood cells isolated from the same patient. An antibody (5F9) was selected which bound to fresh tumor cells from two patients with embryonal testicular carcinoma and failed to bind to fresh tumor cells from 24 patients (2 seminoma, 2 melanoma, 3 neck, 2 esophageal, 1 ovarian, 3 colon, 1 prostate, 2 breast, 1 liposarcoma, 3 endometrial, 1 kidney, 1 adrenal, 1 larynx and 1 bladder tumors) or cell suspensions prepared from normal liver, lung, spleen, ovary, testes, kidney, red blood cells or white blood cells. The antibody was tested for its binding to several well established cancer cell lines, and was found to bind to the BeWo human choriocarcinoma and two human embryonal carcinoma cell lines. The antibody did not react with 22 other cell lines or with hCG. The antibody was labeled with 131I and injected into nude mice bearing BeWo tumors and evaluated for tumor localization by performing whole body scans with a gamma camera 5 days later. Six mice injected with the antibody showed positive tumor localization without the need for background subtraction while six mice injected with MOPC-21, a murine myeloma immunoglobulin, demonstrated much less tumor localization. Tissue distribution studies performed after scanning showed specific tumor localization (8:1 tumor: muscle) for the monoclonal antibody and no specific localization for MOPC-21. This antibody thus has selective reactivity with the surface of tumor cells from embryonal carcinoma (testicle) and choriocarcinoma both in vitro and in vivo.     

Indomethacin and flurbiprofen speed recovery of rat bronchial epithelium after exposure to cigarette smoke

The cigarette smoke-induced rat model of chronic bronchitis was used to study the time course of the return of cigarette smoke-induced secretory cell hyperplasia to the normal and the capacity of two non-steroidal anti-inflammatory drugs to speed this recovery. Cigarette smoke alone significantly increased (P less than 0.05) the number of secretory cells in all of the eight airway levels studied to between 52-225% above control values. After cessation of exposure, recovery was complete by 9 days in the trachea, between 10-21 days in 'proximal' intrapulmonary airways and 43-84 days in distal bronchioli. Indomethacin and flurbiprofen, given by intraperitoneal injection at 4 mg/kg body weight for 21 days of the recovery period, significantly reduced the time taken for recovery to between 4 and 9 days in intrapulmonary airways but had no effect in the trachea.     

Is EMDR an exposure therapy? A review of trauma protocols

This article presents the well established theoretical base and clinical practice of exposure therapy for trauma. Necessary requirements for positive treatment results and contraindicated procedures are reviewed. EMDR is contrasted with these requirements and procedures. By the definitions and clinical practice of exposure therapy, the classification of EMDR poses some problems. As seen from the exposure therapy paradigm, its lack of physiological habituation and use of spontaneous association should result in negligible or negative effects rather than the well researched positive outcomes. Possible reasons for the effectiveness of EMDR are discussed, ranging from the fundamental nature of trauma reactions to the nonexposure mechanisms utilized in information processing models.     

Mixed organic brain syndrome as a manifestation of systemic mastocytosis

Systemic mastocytosis is a disease characterized by an excessive accumulation of mast cells, and associated with skin lesions, flushing, diarrhea, tachycardia, and psychiatric manifestations. In order to define more clearly the psychiatric manifestations, ten patients with this disorder underwent unstructured psychiatric interviews and a battery of psychologic testing. Both revealed a pattern of cognitive and affective changes in the majority of these patients, best categorized as an atypical or mixed organic brain syndrome. The cognitive changes consisted of diminished attention and memory, and the affective changes of anger, irritability, and, to a lesser extent, depression. These manifestations fluctuated with the level of disease activity, and appeared in some cases to respond to histamine antagonists and disodium cromoglycate, medications used to control the excessive mast cell activity. It is important for psychiatrists to be aware that mental status changes can represent psychiatric manifestations of mastocytosis, a readily treatable medical disorder.     

Mycoplasma pneumoniae Induces Chronic Respiratory Infection, Airway Hyperreactivity, and Pulmonary Inflammation: a Murine Model of Infection-Associated Chronic Reactive Airway Disease

Because chronic Mycoplasma pneumoniae respiratory infection is hypothesized to play a role in asthma, the potential of M. pneumoniae to establish chronic respiratory infection with associated pulmonary disease was investigated in a murine model. BALB/c mice were intranasally inoculated once with M. pneumoniae and examined at 109, 150, 245, 368, and 530 days postinoculation. M. pneumoniae was detected in bronchoalveolar lavage fluid by culture or PCR in 70 and 22% of mice at 109 and 530 days postinoculation, respectively. Lung histopathology was normal up to 368 days postinoculation. At 530 days, however, 78% of the mice inoculated with M. pneumoniae demonstrated abnormal histopathology characterized by peribronchial and perivascular mononuclear infiltrates. A mean histopathologic score (HPS) at 530 days of 5.1 was significantly greater (P < 0.01) than that for controls (HPS score of 0). Serum anti-M. pneumoniae immunoglobulin G was detectable in all of the mice inoculated with M. pneumoniae and was inversely correlated with HPS (r = -0.95, P = 0.01) at 530 days postinoculation. Unrestrained whole-body plethysmography measurement of enhanced pause revealed significantly elevated airway methacholine reactivity in M. pneumoniae-inoculated mice compared with that in controls at 245 days (P = 0.03) and increased airway obstruction at 530 days (P = 0.01). Murine M. pneumoniae respiratory infection can lead to chronic pulmonary disease characterized by airway hyperreactivity, airway obstruction, and histologic inflammation.     

Is the grading of breast carcinomas affected by a delay in fixation?

Summary The effect of delay in fixation on the modified Bloom and Richardson grade of eight breast carcinomas was investigated. Topologically shuffled samples of each tumour were immersed in fixative at times of 0.5, 2, 4, 6, 18 and 24 h after surgical removal. The grade of each tumour was assessed at delays of 0.5 and 6 h. The tubule formation and nuclear pleomorphism components of the grade showed no change with a delay in fixation of 6 h. The number of mitotic figures declined by a mean of 53% over the same period and this resulted in a decrease in the histological grade of one of the tumours. The implications of these findings for the handling of breast specimens in a diagnostic histopathological laboratory are discussed.Some of these data were presented at the 162nd meeting of the Pathological Society of Great Britain and Ireland at Cambridge, 3 January 1991. Published as an abstract in J Pathol (1991) 163:154A     

Cognitive impairment after unilateral hemispheric injury of congenital or adult origin.

OBJECTIVE: The purpose of this study was to assess and compare cognitive functioning in adults with unilateral hemispheric injury due to either congenital damage or an ischemic event in young adulthood. METHOD: Adults with cerebral palsy resulting from left hemispheric brain damage were compared with adults who had a unilateral stroke in either the left or the right hemisphere. Our primary interest was to determine the impact on hemispheric dominance as revealed by dichotic listening, a task that assesses the bias for preferential listening and processing of sounds. Performance also was determined on a language-related task (word finding) and a spatial task (dot localization). RESULTS: Scores on the Quick Neurological Screening Test indicated that all participants demonstrated significant neuromotor deficits, whereas scores on the Barthel Index indicated that the participants were functional in basic activities of daily living. On cognitive assessments, healthy control participants demonstrated a pronounced left-hemisphere dominance and right-ear advantage; participants with injury to the left hemisphere showed a strong shift toward a right-hemisphere and left-ear dominance. In particular, injury of congenital origin appeared to foster this neural reorganization and localization of language-related functions into the healthy hemisphere. This shift was associated with a deterioration of performance on both the language and the spatial tasks. CONCLUSION: The importance of appreciating subtle deficits after unilateral injury is important in therapy. The dichotic listening test may provide a simple and useful means for evaluating persistent unilateral brain dysfunction in the clinical setting.     

The functioning and well-being of depressed patients. Results from the Medical Outcomes Study

We describe the functioning and well-being of patients with depression, relative to patients with chronic medical conditions or no chronic conditions. Data are from 11,242 outpatients in three health care provision systems in three US sites. Patients with either current depressive disorder or depressive symptoms in the absence of disorder tended to have worse physical, social, and role functioning, worse perceived current health, and greater bodily pain than did patients with no chronic conditions. The poor functioning uniquely associated with depressive symptoms, with or without depressive disorder, was comparable with or worse than that uniquely associated with eight major chronic medical conditions. For example, the unique association of days in bed with depressive symptoms was significantly greater than the comparable association with hypertension, diabetes, and arthritis. Depression and chronic medical conditions had unique and additive effects on patient functioning.