The nephrogram of normovolemic, renal artery hypotension.

Experimental hemorrhagic hypotension results in a prolonged nephrogram during excretory urography. We evaluated the effect of reduced renal perfusion pressure on the nephrogram in normovolemic dogs. Renal artery perfusion pressure to one kidney was reduced to 40-50 mm Hg by inflating a renal artery balloon catheter. Subsequent urograms were qualitatively assessed for nephrographic density. Plasma and urinary iodine concentrations were determined by fluorescent excitation analysis. Total renal blood flow (TRBF) and its intrarenal distribution were assessed with isotopically labeled microspheres. In the majority of dogs severe oliguria and a prolonged and increasingly dense nephrogram were produced in the kidney exposed to reduced perfusion pressure. The nephrogram of the contralateral, normotensive kidney rapidly diminished in density, associated with the excretion of a large volume of dilute urine. The total urinary iodine excreted in 60 min was significantly less than that excreted by both kidneys in control experiments. TRBF to the hypotensive kidney was significantly reduced from its control level, and the percentage of TRBF perfusing the outer cortex decreased.     

Myotonic dystrophy as a disease of abnormal membrane receptors: An hypothesis of pathophysiology and a new approach to treatment

Muscle weakness, clinical myotonia, and multiple systemic organ disturbances characterize myotonic dystrophy. Many of these systemic disturbances involve target organ insensitivity to aminergic or peptidergic (hormonal) stimulation. Reduced density or impaired function of aminergic and peptidergic (hormonal) receptors throughout the body may underlie this disorder. Tricyclic antidepressant augmentation of aminergic function ameliorates depressive symptoms, increases strength, and improves clinical myotonia in myotonic dystrophy patients.     

Effect of acute and repeated chlordimeform treatment on rat hepatic microsomal drug metabolizing enzymes

The effect of chlordimeform (CDM) treatment on the hepatic microsomal drug metabolizing enzymes was examined in male and female rats following either acute or repeated treatment. After acute administration of chlordimeform (100 mg/kg, i.p., 1 hour before killing) differential effects were observed in various parameters of the hepatic microsomal mixed function oxidase system with significant decreases in ethylmorphine metabolism, cytochrome P-450 content, NADPH cytochrome c reductase, and in the spectral binding of hexobarbital and aniline while no changes were found in the metabolism of aniline or p-nitroanisole. Durations of zoxazolamine-induced paralysis and pentobarbital-induced hypnosis were increased significantly after acute CDM administration. Following repeated administration of CDM (75 mg/kg, i.p., for 4 days) to adult male rats, a decrease was observed in zoxazolamine-induced paralysis time while pentobarbital-induced hypnosis was not altered. Metabolism studies using isolated hepatic microsomal fractions showed a decreased rate of biotransformation of ethylmorphine and aniline while the activity of p-nitroanisole O-demethylase was not changed. No differences were found in cytochrome P-450 levels whereas microsomal spectral binding of hexobarbital was reduced while that of aniline was not affected. Following acute or repeated administration of CDM to adult female rats, decreases in the hepatic microsomal metabolism of aniline, but not ethylmorphine or p-nitroanisole, were observed. Addition of CDM to microsomal suspensions yielded a Type I binding curve.     

Endocapsular hypopyon: a clinical sign of localized endophthalmitis

Chronic intraocular infection following cataract extraction and intraocular lens (IOL) implantation has been documented by several authors. We report a case of chronic, bacterial endophthalmitis that clinically correlates with previous pathologic studies in which the focus of infection was sequestered in the capsular sac between the IOL and the posterior lens capsule. Successful management did not require IOL removal.     

Antibody-directed superantigen-mediated T-cell killing of myeloid leukaemic cell line cells

Abstract: Bacterial superantigens (SAgs) bound to MHC class II molecules on target cells are efficient activators of cytotoxic T cells expressing certain T cell receptor (TCR) Vβ regions. We described earlier that the specificity of the SAg Staphylococcus enterotoxin A (SEA) can be changed by introducing a D227A point mutation in the major MHC class II binding site and by genetically fusing the SEA mutant (SEAm) to protein A (PA). This SEAm-PA fusion protein can then be used to direct cytotoxic T cells to tumour cells coated with monoclonal antibodies (mAbs). In this communication, we tested the PA-SEAm fusion protein together with mAbs against the myeloid cell surface antigens CD13, CD15 and CD33. A SEA-reactive T cell line was used as effector cells against 10 different myeloid leukaemic cell lines. Optimal lysis of antigen positive leukaemic cells was obtained at a PA-SEAm concentration of 1 ng/ml and effector: target cell ratios of 15 : 1. No correlation between target cell sensitivity and the level of surface antigen expression could be seen. The 6 acute myeloid leukaemia (AML) cell lines tested appeared to be more sensitive than the 4 chronic myeloid leukaemia (CML) cell lines. The sensitivity of the AML cell line HL-60 could be improved further by stimulation with TNFα. This was accompanied by increased surface ICAM-1 expression whereas specific target molecule expression (CD13, CD33) was unchanged. This suggests that sensitivity to lysis is related to the leukaemic subtype and ICAM-1 expression but not to the tumour antigen density. Our results show that it is possible to direct cytotoxic T cells to myeloid leukaemia cells by using SAgs linked to mAbs, and encourage the construction and testing of a recombinant direct SAg-mAb fusion protein as a candidate drug for therapy of myeloid leukaemias.     

Twenty-Four-Hour Ambulatory Blood Pressure and Heart Rate Monitoring in Combat-Related Posttraumatic Stress Disorder

This study examined the cardiovascular correlates of posttraumatic stress disorder (PTSD) in Vietnam combat veterans using 24-hr ambulatory blood pressure and heart rate monitoring. Veterans with PTSD (n = 11) exhibited significantly higher heart rate and diastolic blood pressure across the 24 hr than veterans without PTSD (n = 7) (80.8 vs. 71.9 bpm, and 80.1 vs. 71.5 mm Hg, respectively). Heart rate during sleep was also significantly higher among veterans with PTSD, compared to veterans without PTSD (71.0 vs. 62.7 bpm). These results, based on a more naturalistic measurement methodology used outside the laboratory, support an association between PTSD and increased chronic cardiovascular arousal.     

Selection for B cells with productive IgL gene rearrangements occurs in the bursa of Fabricius during chicken embryonic development

The vast majority of immunoglobulin-expressing mature chicken B lymphocytes contain one functionally rearranged and one unrearranged allele of the immunoglobulin light chain (IgL) gene. Therefore, nearly all IgL V-J rearrangements present in mature chickens are in-frame. In contrast, the Ig genes of mature mammalian B cells contain a high proportion of out-of-frame V-J joints. To investigate the basis for this difference, gene rearrangement at the chicken IgL locus was characterized during embryonic development and in mature B-cell lines. Joining of the single functional variable (VL) segment with the single joining (JL) segment occurs in cells in multiple tissues during a transient period of chicken embryogenesis. Only one-third of the V-J joints cloned from days 10-12 of development are in-frame. An increasing proportion of in-frame V-J joints is observed within the bursa of Fabricius at successively later stages of development. Our data suggest that the bursa of Fabricius serves during embryonic development as a site of selective amplification of cells that have undergone productive V-J joining, such that nearly all V-J joints present in postembryonic B cells are in-frame. The high frequency of rearranged alleles joined in-frame that is found in posthatching bursal cells and mature B-cell lines appears to result from a low frequency with which cells undergo IgL rearrangement at both alleles, rather than from an increase in the precision of V-J joining in avian species.