Enhanced binding of low-affinity antibodies interacting simultaneously with targeted cell surface molecules and Fc receptor.

The possibility that different forms of class I molecules might be expressed on the cell surface of lymphocytes has been investigated periodically over the past several decades. A series of major histocompatibility complex (MHC) class I-specific monoclonal antibodies, including the commonly used antibodies 64-3-7 and 25-D1.16, bind B cells differentially, suggesting the existence of differentially expressed class I-associated cell surface determinants on B lymphocytes. However, the ability of antibodies to bind cells is determined by the sum of interactions between the antibodies and the molecules expressed on the cell surface. The interactions of class I-specific antibodies with B cells were dissected, revealing dual specificity of the antibodies for the targeted class I molecules, as well as to Fc receptors preferentially expressed by B cells. We demonstrate that antibodies simultaneously bind targeted class I molecules and Fc receptors expressed on the surface of B cells. Simultaneous binding to two cell surface structures significantly enhances the class I-specific binding pattern of certain antibodies by increasing their avidity, leading to apparent cell-specific differences in MHC expression patterns. We conclude that no differences in MHC structures need be postulated to account for the observed binding patterns.

A common mutation in the hominoid class I A-locus IFN-responsive element results in the loss of enhancer activity.

Despite the observed coordinate expression of HLA-A and -B antigens in somatic tissues, there is growing evidence that the A and B class I genes are differentially regulated at the transcriptional level. Previous studies indicate that this may be related to locus-specific structural differences in certain enhancer elements. We have recently examined the 5' proximal regulatory regions of the A and B homologs in the higher non-human primates and found pronounced differences between the loci. Sequence analysis shows the B-promoters are more homogeneous, whereas the A-locus promoters are divergent among the various species examined. The differences in A- and B-promoters is exemplified by the regulatory element referred to as the IFN-responsive element (IRE). While the B-locus IRE is conserved among all primates examined, the A-locus IRE are divergent and reveal different sequences in the human/chimpanzee, gorilla and orang-utan. In reporter gene bioassays, the B-locus IRE exhibited an enhancer activity in response to induction with IFN-beta and IFN-gamma. In contrast, all the variants of the A-locus IRE found in hominoid primates were unresponsive to IFN. One base substitution shared by all the primate IREs proved to be inactivating. These results provide a molecular basis of how duplicated gene loci encoding structurally and functionally similar antigen-presenting molecules may become differentially responsive to physiological stimulus.

Amino acid changes in the peptide binding site have structural consequences at the surface of class I glycoproteins.

Structural changes on the surface of the class I Ag binding domain resulting from point mutations localized inside the Ag binding cleft of the H-2Kb and Kf glycoproteins were revealed using mAb. Both the loss and gain of antibody binding sites found among naturally occurring K glycoproteins resulted from single amino acid substitutions at a variety of different positions buried within the Ag binding groove. Each of the amino acid replacements analyzed represented naturally occurring diversity known to exist among the functional class I Ag-presenting molecules of the mouse. The binding of the affected mAb was not significantly altered in Kb molecules expressed by transfected T2 cells. Because T2 cells have been shown to express Kb molecules that are either largely devoid of bound peptides or bind a vastly different set of low affinity peptides, it is unlikely that the detected structural changes were caused by alterations in the spectrum of peptides bound by the class I variant glycoproteins. Similarly, a class I point mutant, Kb-97R, that also has been shown previously to bind a very different set of peptides in comparison to the parental Kb molecule also displays normal antibody binding properties. We conclude from these studies that structural diversity within the Ag binding cleft indirectly influences the external surface of the Ag-presenting domain of the class I H chain. Significantly, this surface is the interface between the T cell receptor and MHC molecules and may make contributions to the fine specificity of allorecognition.

Behavioral and neuroanatomical sequelae of prenatal naloxone administration in the rat.

Pregnant Long-Evans hooded rats were dosed subcutaneously with 1 or 5 mg/kg/day naloxone hydrochloride, or an equal volume of vehicle, from gestational Day 4 (GD4) through GD19. Offspring were assessed for development of righting reflex, negative geotaxis, and open field activity, and for acquisition of a Warden maze; offspring sacrificed at postnatal Day (PND) 21 were assessed for several parameters of cerebellar, hippocampal, and motor cortical morphology. Five mg/kg/day naloxone accelerated development of negative geotaxis and righting reflex, while 1 mg/kg/day naloxone tended to slow development. Low dose females had significantly more errors than controls on the first day of maze learning. The high dose group had a significantly higher concentration of granule cells in the curvature of the dentate gyrus than controls; other neuroanatomical measures were unaffected by dosing. These findings confirm and extend previous work indicating that prenatal exposure to naloxone may alter neurobehavioral development in the rat.

Age-related changes of the prostate: evaluation by MR imaging.

The pelvic MR examinations of 40 men without known prostatic disease were reviewed retrospectively. Axial long TR/long TE images were evaluated with respect to prostatic zonal size and signal intensity. Findings were correlated with each patient's age (17-74 years). The central region of the prostate and the peripheral zone enlarged with age; the central gland increased in size by an average of 175% between the second and eighth decades and the peripheral zone increased by an average of 67%. The anterior fibromuscular stroma decreased with increasing age (from an average anteroposterior thickness of 1.2 cm in the second decade to 0.4 cm in the eighth decade) and also became thinner as a function of increasing gland size. The periprostatic venous plexus became less prominent as a function of increasing age, decreasing from 2.5 to 1.5 mm in average maximal diameter, but this venous caliber was not significantly correlated with gland size. The conspicuity of the peripheral zone with respect to the central gland was improved, both as a function of increasing age and increasing gland size, and conspicuity was greatest on long TR/long TE images because of excellent contrast resolution. We conclude that in older age groups, the zonal anatomy of the prostate is more clearly defined than in young patients, both because of morphologic changes in prostate structure and because of physiologic changes resulting in differing zonal MR signal intensities.

Prostatic carcinoma: staging with MR imaging at 1.5 T.

Magnetic resonance (MR) imaging was used to stage prostatic carcinoma in 81 patients with a proved diagnosis. MR imaging findings were correlated with histologic findings regarding the local extent of disease (37 patieNts) and the presence of nodal metastases (51 patients). Tumor nodules were detected in the peripheral zone (PZ) in 34 of 37 patients and were of low signal intensity compared with the signal of the PZ. Hemorrhage in the PZ represented a problem in tumor detection and in tumor volume measurement. When multiple criteria for local tumor spread were combined, MR imaging had a sensitivity of 72%, a specificity of 84%, and an accuracy of 78% in the differentiation of stage A or B from Stage C or D disease. Assessment of seminal vesicle invasion was more accurate than assessment of direct extracapsular spread. In five patients, microscopic invasion of the capsule (stage C) was classified as stage B with MR imaging; from a clinical standpoint, this should not affect patient treatment and prognosis. The MR imaging sensitivity in the detection of lymph node metastases was 69%, with a specificity of 95% and an accuracy of 88%. In this study MR imaging proved reliable in the comprehensive evaluation and staging of prostatic carcinoma.

Renal allografts: prospective analysis of Doppler sonography.

Fifty-six consecutively transplanted renal allografts were prospectively evaluated with serial Doppler sonographic examinations. Thirty-eight episodes of transplant rejection in 32 patients (63% proved pathologically) and 24 episodes of acute tubular necrosis (ATN) in 24 patients were encountered. The Doppler spectral waveform was characterized by means of the pulsatility index (PI), systolic/diastolic ratio (SDR), diastolic/systolic ratio (SDR), diastolic/systolic ratio (DSR), and resistive index (RI). Accuracy was optimized with use of top normal values as follows: PI = 1.8, SDR = 4.0, DSR = 0.25, RI = 0.75. There were no significant differences in the indices for those patients undergoing rejection versus those with ATN. The sensitivity for predicting transplant rejection was adversely affected by the history of either ATN or a previous rejection episode in the same allograft. Comparison with concurrent radionuclide examinations revealed similar sensitivities for rejection with scintigraphy and sonography. Differentiation of ATN from rejection was more reliable with scintigraphy than with sonography.

Transvaginal and transabdominal sonography: prospective comparison.

Transvaginal (TV) and transabdominal (TA) sonography were compared in a prospective study. A total of 230 examinations (126 pelvic, 104 pregnancy) were performed on 215 patients, ranging in age from 14 to 80 years. The improved anatomic detail on TV scans yielded new information in 138 (60%) examinations and better visualization of pelvic structures in 51 (22%) examinations. There was no important difference in diagnostic information provided by the two imaging modalities in 36 (16%) cases, and TV images were worse in five (2%). The clinical diagnosis was altered on the basis of TV sonographic findings in 54 (24%) cases and confirmed with certainty in 166 (72%). Diagnostic problems posed by TA scanning were not resolved by TV scanning in ten (4%) instances. Statistical analysis indicated that TV scanning was significantly better than TA scanning in the visualization of gestational sac contents (P less than .005), detection of fetal heart motion (P less than .001), and evaluation of the endometrial canal in the retroverted or retroflexed uterus (P less than .001). TV scanning was significantly better than TA scanning in visualization of the ovaries in patients with uterine leiomyomas (P less than .005) but not significantly better in peri- and postmenopausal patients (P greater than .05).

Cryptococcosis associated with sarcoidosis: CT and MR findings.

Two cases of cryptococcal abscesses were identified in patients with sarcoidosis. The diagnostic imaging tests were not specific for cryptococcus prior to needle aspiration of the abscesses, but they did enable successful biopsy for diagnosis and treatment.

Effects of maternal hydration on fetal renal pyelectasis.

Fetal renal pyelectasis is a frequent finding on routine obstetrical sonography. The cause of this pelvocalyceal dilatation is often not apparent, although urinary tract obstruction is the most important condition to be excluded. One of the many hypothetical explanations for minimal fetal renal pyelectasis suggests that aggressive maternal hydration before sonography leads to fetal diuresis with resultant pelvocalyceal dilatation. In this study, 20 pregnant volunteers underwent sonography after 10-12 hours of dehydration, after which 1,000 ml of fluid was administered and repeat sonography was performed. Despite a significant increase in the state of maternal hydration as determined by a decrease in urine specific gravity, there was no significant change in the degree of fetal renal pyelectasis before and after hydration. Therefore, pelvocalyceal dilatation identified prenatally should not be attributed to maternal hydration.

Perforation of distal esophagus with lesser sac extension: CT demonstration.

Two cases of esophageal perforation with abdominal extension are described. Radiographic and clinical aspects are discussed with the emphasis on CT as the modality of choice for demonstrating the location and extent of extraesophageal involvement.

Factors affecting physicians' choice to practice in a fee-for-service setting versus an individual practice association.

Individual Practice Associations (IPAs) must be able to recruit physicians from the community to compete in the future. This article reports the results of a study to assess the factors that influenced physicians in the Research Triangle area of North Carolina to join a primary care network type of IPA. Results indicate that physicians with lower incomes and fewer physician visits and those who were newly established in the community were more likely to join. Peers had a strong influence on their decisions, while Blue Cross/Blue Shield marketing representatives did not.