Ki-ras MUTATIONS IN ADENOMAS: A CHARACTERISTIC OF CANCER-BEARING COLORECTAL MUCOSA

Activating mutations in the Ki- ras 2 oncogene are frequently observed in sporadic colorectal adenomas and their incidence is reported to rise in large and tubulovillous adenomas to values close to those in carcinomas. This study shows that this property is a feature of adenomas growing in large bowel that has already demonstrated its propensity to engender malignant tumours: i.e., bowel in which there is a synchronous carcinoma. Adenomas from cancer-free bowel do not share this high incidence of Ki- ras mutations. This difference in mutation incidence between adenomas from cancer-free and cancer-bearing patients does not appear to derive from sampling bias relative to adenoma size, site, or patient age, nor is it found in another gene (APC) known to be of importance in adenoma formation. Large, dysplastic adenomas from cancer-bearing bowel, however, are particularly liable to carry Ki- ras mutations when they arise in patients over 70 years old. The observations suggest that the role of Ki- ras mutations may be more subtle than merely enhancing adenoma growth. Adenoma cells of cancer-prone individuals may suffer more mutational events than those in persons selected as cancer-free.     

CONGENITAL ANTERIOR URETHROCUTANEOUS FISTULA

PURPOSE: Congenital anterior urethrocutaneous fistula is a rare anomaly that may present in an isolated fashion or in association with other penile abnormalities, such as chordee or hypospadias. There have been 18 cases of congenital anterior urethrocutaneous fistula reported in the literature. We present 14 additional cases of congenital anterior urethrocutaneous fistula. MATERIALS AND METHODS: We treated 14 patients with congenital anterior urethrocutaneous fistula, of whom 9 were uncircumcised at presentation. Two patients had evidence of chordee and 4 had distal hypospadias. RESULTS: The type of repair was determined by the anatomical variations of this anomaly. All cases were corrected electively by various techniques based on the degree of the defect, including primary closure via a Thiersch-Duplay urethroplasty, pedicle flap urethroplasty, hinged flap urethroplasty and interpositioned island pedicle tube or onlay urethroplasty. CONCLUSIONS: To our knowledge the embryological events that cause anterior urethrocutaneous fistula are unclear but they likely result from a defective urethral plate or an abnormality of the infolding of the urethral groove. Surgical technique must be individualized to fit the defect. While there has been considerable skepticism regarding the existence of congenital urethrocutaneous fistula, the fact that 9 of our 14 patients were uncircumcised confirms the congenital nature of this lesion.     

Attentional modulation of startle in psychosis-prone college students

Attentional modulation of startle eyeblink was studied in college students putatively at risk for psychosis and in normal controls. At-risk subjects had extreme scores on scales for either anhedonia or perceptual aberration-magical thinking (per-mags). Subjects were presented with to-be-attended and to-be-ignored tones; white noise startle probes were presented at lead intervals of 60, 120, 240, or 2,000 ms following the onset of attended and ignored tones and during intertone intervals. Controls showed greater inhibition of startle blink at 120 ms and greater facilitation at 2,000 ms during to-be-attended than to-be-ignored tone, demonstrating attentional modulation of prepulse inhibition and facilitation. Both at-risk groups showed normal overall levels of early inhibition and late facilitation. However, per-mags failed to show attentional modulation of either inhibition at 120 ms or facilitation at 2,000 ms; anhedonics showed no modulation of inhibition and modulation of facilitation was delayed in development. The results for the per-mags are strikingly similar to those observed in schizophrenic patients and suggest that these deficits index a trait-linked vulnerability to disorders in the schizophrenic spectrum.     

Genetic control of immunity to Heligmosomoides polygyrus: presentation of promiscuous antigens to parasite-specific T cell hybridomas

The role of MHC class II in the presentation of Heligmosomoides polygyrus antigens has been investigated, using a number of T cell hybridomas produced in A and E positive and negative mice. By using fixed and irradiated antigen presenting cells (APC), further evidence has emerged, to support earlier data, that there can be differential processing requirements during the presentation of H. polygyrus antigens by A and E molecules. In concordance with these earlier observations, this work provides further evidence that individual T cells can respond to antigen when presented by more than one MHC molecule. Previously, this evidence has been restricted to individual MHC molecules of the same haplotype, hut these data show that H. polygyrus produces antigens which can he presented by both syngeneic and allogeneic MHC molecules. These antigens do not appear to be synonymous with the previously described H. polygyrus superantigen, as presentation is restricted to specific MHC haplotypes. It is proposed that H. polygyrus may produce these antigenic molecules as part of its strategy to manipulate the host immune system.     

Expression of the Plasmodium berghei ookinete protein Pbs21 in a baculovirus-insect cell system produces an efficient transmission blocking immunogen

A surface protein of Plasmodium berghei ookinetes, Pbs21, was expressed in a baculovirus-insect cell system in cell culture and in Heliothis virescens larvae. Groups of BALB/c mice received two intraperitoneal inoculations of either i) Tris-buffer or homogenized H. virescens larvae infected with wild-type baculovirus; ii) enriched, homogenized ookinetes, or Hi) homogenizedH. virescens larvae expressing recombinant Pbs21 (rPbs21). All animals immunized with ookinetes or with rPbs21 had high litres of antibodies (IgG isotype) that bound to native Pbs21. The large majority of antibodies in immune sera of both groups recognized the antigen under non-reducing but not under reducing conditions. The predominant IgG-sub-classes in mice immunized with ookinetes was IgGl and in mice immunized with rPbs21, the subclasses were IgGl and IgG2a. Immunization with rPbs21 reduced the infec-tivity of P. berghei to mosquitoes by 91% compared to a 99% reduction following immunization with ookinetes. This preliminary data indicate that rPbs21 expressed in this eukaryotic system induces a transmission-blocking immunity which is more effective than that achieved using rPbsll expressed in Escherichia coli (Matsuoka et al. 1994).     

Masquerading Bundle-Branch Block—Electrophysiological Correlation

The term masquerading bundle-branch block has been used to describe a peculiar electrocardiographic abnormality in which the standard leads exhibit a left bundle-branch block pattern while the precordial leads manifest a right bundle-branch configuration. Autopsy studies of patients who have had this electrocardiographic pattern in life have shown diffuse conduction system disease, but direct recordings of conduction system function have never been reported. We recently cared for a man with masquerading bundle-branch block, and in this report we summarize the results of invasive electrophysiological testing. Our findings confirm that masquerading bundle-branch block can be associated with severe and diffuse conduction system disease, and that patients with this finding may require permanent pacemaker implantation, especially if they are symptomatic.     

Timing of the Upper Limit of Vulnerability is Different for Monophasic and Biphasic Shocks: Implications for the Determination of the Defibrillation Threshold

The upper limit of vulnerability (ULV) has been used in clinical studies to predict the DFT in patients with ICDs. Despite the ULV-DFT correlation, uncertainties about the optimal timing of the ULV determination remain. Previous studies using monophasic or biphasic shock waveforms reported differences in the ULV timing with respect to the electrocardiographic T wave. The purpose of this study was to directly compare the ULV timing for mono- versus biphasic T wave shocks. In ten isolated rabbit hearts, mono- and biphasic shocks were delivered randomly during the vulnerable window and at varying shock strengths to determine the ULV. The ULV timing was expressed as the coupling interval at the ULV, the myocardial repolarization state at the ULV measured by monophasic action potential recordings, and the relation between the ULV and the peak of the simultaneously recorded volume conducted T wave. The ULV for biphasic shocks occurred at longer coupling intervals than for monophasic shocks (188.0 ± 9.5 ms vs 173.5 ± 8.8 ms, P < 0.001). This resulted in a more repolarized myocardial state at the ULV for biphasic than for monophasic shocks (81.1%± 7.5% vs 66.9%± 9.0%, P = 0.002). The ULV for monophasic shocks occurred predominantly during the upslope of the T wave (8.0 ± 9.7 ms before the peak of the T wave) whereas the ULV for biphasic shocks occurred at or after the peak of the T wave (5.9 ± 9.3 ms after the peak of the T wave) (P < 0.001). Biphasic shocks delay the timing of the ULV as compared to monophasic shocks. This is important for the prediction of the DFT by ULV measurements.