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Biomedical subjects

M Kessler

Publications and source records attributed to M Kessler.

At least 91 records · Page 5Linked to original sources
PubMed1997

Sialic acid residues indirectly modulate the binding properties of AMPA-type glutamate receptors.

Manipulations that disrupt the extracellular interactions of neural cell adhesion molecules (NCAMs) block the formation of stable long-term potentiation (LTP) but do not reverse already established potentiation. Several studies have implicated a change in AMPA-type glutamate receptors as being responsible for the expression of LTP but there are no evident links between NCAMs and the receptors. NCAMs are major carriers of sialic acid residues in the brain and removal of these with neuraminidase markedly affects the binding properties of the adhesion molecules. Therefore, the present study tested if neuraminidase treatment produces a change in AMPA receptors. Preincubation of cortical membranes with the enzyme for 15 min at 37 degrees C caused a approximately 5% reduction in the apparent sizes of NCAMs 140 and 180 but had no detectable influence on the sizes of various glutamate receptor subunits. The same treatment resulted in a 20 +/- 1% increase in the binding of [3H]AMPA with no apparent effect on binding to NMDA-type glutamate receptors or to high affinity kainate receptors. In membranes from the hippocampus, neuraminidase induced a 30 +/- 2% increase in binding which Scatchard analyses showed to be due to an increase in receptor affinity. Finally, neuraminidase had no effect on either the binding properties of solubilized AMPA receptors or on AMPA receptors stably expressed in a non-neuronal cell line. These results: (i) demonstrate that modulation of the extracellular environment can influence the binding properties of AMPA receptors, (ii) indicate that sialic acid residues in the extracellular compartment of synapses exert a significant and indirect influence on AMPA receptors and, (iii) suggest a route whereby NCAMs and LTP could be linked.

Animals↗
PubMed1997

Enhanced expression of CD31 and CD54 on tonsillar high endothelial venules in IgA nephropathy.

Abnormalities in the partition of IgA- and IgG-producing cells in the tonsils of patients with IgA nephropathy have been suggested to result from a dysregulation of cell trafficking and homing through high endothelial venules in this lymphoid tissue. In order to document such adhesion anomalies, we used the 36 monoclonal antibodies of the cell adhesion molecules subpanel of the Fifth International Workshop on Leukocyte Differentiation Antigens on frozen sections of tonsils from 10 patients and 15 controls. This allowed us to describe the partition of cell adhesion molecules in human tonsils and to demonstrate a significant enhancement of CD31 and CD54 expression on high endothelial venules of tonsils from patients with IgA nephropathy. These observations are in keeping with the hypothesis of an increased lymphocyte recruitment in tonsils in this disease.

Adolescent↗
PubMed1997

Evidence that a positive modulator of AMPA-type glutamate receptors improves delayed recall in aged humans.

Elderly subjects (65-76 years) were tested for recall of nonsense syllables prior to and after oral administration of 1-(quinoxalin-6 ylcarbonyl)piperidine (CX516), a centrally active drug that enhances currents mediated by AMPA-type glutamate receptors. A significant and positive drug effect was found for delayed (5 min) recall at 75 min posttreatment; average scores for the highest dose group were more than twofold greater than for the placebo group. The drug had no evident influence on heart rate or self-assessment of several psychological variables.

Aged↗
PubMed1997

Enhancement by an ampakine of memory encoding in humans.

Acentrally active drug that enhances AMPA receptor-mediated currents was tested for its effects on memory in humans. Evidence for a positive influence on encoding was obtained in four tests: (i) visual associations, (ii) recognition of odors, (iii) acquisition of a visuospatial maze, and (iv) location and identity of playing cards. The drug did not improve scores in a task requiring cued recall of verbal information. The selectivity of drug effects on memory was confirmed using tests of visual recognition, motor performance, and general intellectual functioning. These results suggest that positive modulators of AMPA receptors selectively improve at least some aspects of memory.

Adult↗
PubMed1997

[Computer-assisted evaluation of mammography images. Initial clinical experiences].

UNLABELLED: Preceding studies have shown that a second independent reviewer of conventional mammographies increases the detection rate of features typical for malignancy by up to 15%. METHODS: In order to test a computer-aided diagnostic (CAD) system (ImageChecker, R2 Technology, USA) for the detection of pathologic criteria in conventional mammography, 96 mammographies were retrospectively evaluated using ImageChecker. Thirty-five of these mammographies had been diagnosed as not showing pathologies, and 61 had depicted histologically confirmed malignancy. RESULTS: Detecting 41 of 61 breast malignancies, ImageChecker showed a diagnostic sensitivity of 70.5%. All malignancies accompanied by microcalcifications were identified by ImageChecker, whereas 18 cases characterized by parenchymal opacity without microcalcifications were not marked. On the average, 1.95 markers per image were set, giving a total of 187 markers in this study. 63% of all markers showed normal tissue and were thus false positive. CONCLUSIONS: Pathologic parenchymal opacities in mammography are a well-known problem for all CAD systems in use. Despite this major drawback, even now ImageChecker can provide tremendous support in routine interpretation of conventional mammographies.

Breast Neoplasms↗
PubMed1997

[Modern ultrasound diagnosis of the female breast. Possibilities and limits].

PURPOSE: The rapid development of sonography made it seem advisable to reconsider the clinical value of breast ultrasound. Our experience with new techniques and current research will be presented. METHODOLOGY: Various indications for breast ultrasound will be discussed. New Doppler techniques extending the ability to detect low blood flow will be presented. RESULTS: The differentiation of suspicious areas seen on mammography and the detection of occult breast cancer are the major challenges in breast ultrasound. A limitation is its low capability to visualize microcalcifications. A promising approach is the development of highly sensitive, color-coded techniques for the detection of minimal blood flow. Another progress is the development of an ultrasound contrast medium that is not inactivated during first lung passage. CONCLUSION: Breast ultrasound provides complementary information to mammography. Using stable ultrasound contrast medium and highly sensitive color-coded Doppler techniques for the detection of minimal blood flow, we hope to find new criteria for the diagnosis of angioneogenesis in breast cancer.

Breast Neoplasms↗
PubMed1997

[MR mammography. Preoperative marking of non-palpable breast lesions with the Magnetom open at 0.2 T].

PURPOSE: To answer the following questions: whether reliable detection of lesions is possible in low-field-MRI-system (Magnetom Open 0.2 T) equipped with currently available hard- and software components in comparison to high field system (Magnetom Impact 1.0 T). Furthermore, whether localization of lesions suspect in MR-mammography can be realized in MR system of low field (Magnetom Open 0.2 T). PATIENTS AND METHODS: In 11 patients, suspect lesions were diagnosed in diagnostic MR-mammography acquired with high field system (Magnetom Impact 1.0 T) and were compared to low field MR-mammographies of 0.2 T (Magnetom Open 0.2 T). In six of the 11 patients a suspect lesion was localized using wire marking. RESULTS: All lesions considered suspect in diagnostic MR-mammography (Magnetom Impact 1.0 T) were also clearly identified in the 0.2 T system (Magnetom Open). In six cases wire marking was performed without any complications and with an accuracy of < or = 0.5 cm distance to the lesion. CONCLUSION: Although studies in the 0.2 T system clearly showed inferior SNR (34.6 vs. 83.1) and CNR (14.6 vs. 43.5) compared to studies with the high field system, all lesions considered suspect in diagnostic MR-mammography were reliably identified also in 0.2 T studies. Due to its open construction permitting permanent access to the breast and due to sufficient image quality, the Magnetom Open is suitable for interventions on the breast.

Biopsy↗
PubMed1997

Low levels of spontaneously activated peripheral IgA-secreting cells in nontransplanted IgA nephropathy patients.

The pathognomonic presence of IgA in the glomerular mesangium of patients with IgA nephropathy (IgAN) suggests an abnormal control of IgA metabolism in this disease that could be modified in transplanted IgAN patients. Alterations of IgA production have been demonstrated in both bone marrow samples and mucosae-associated tissues from IgAN patients, but the analysis of IgA production by peripheral B lymphocytes in culture has yielded conflicting results, some investigators showing an enhanced secretion of IgA and others reporting similar data as with control samples. Little is known about the endogenous activation state of B cells in IgAN, which can be approached by analyzing peripheral Ig-producing cells, a number of which are recirculating between lymphoid organs. In the present study, two methods were applied to appreciate the numbers of spontaneously activated peripheral B cells. The ELISPOT method provided information about short-term secretion of Igs. Intracytoplasmic immunofluorescence for IgA allowed to identify IgA-containing cells, either as short-rimmed immunocytes or as brightly stained immunoblasts with an enlarged cytoplasm. These cells were enumerated in IgAN patients (n = 31), transplanted IgAN patients (n = 27), control patients with other biopsy-proven renal diseases (nontransplanted, n = 48; transplanted, n = 38), and in healthy individuals (n = 18). The number of IgA spot-forming cells obtained in the control groups (1,251 +/- 95 cells/10(6) lymphocytes [mean +/- SE]) was consistent with those in similar previously reported studies, but differed significantly (P = 0.01) from those observed in nontransplanted IgAN patients, who had a surprisingly lower number of such cells (699 +/- 97 cells/10(6) lymphocytes); the number of IgA spot-forming cells in the transplanted IgAN patients (1,355 +/- 182 cells/10(6) lymphocytes) did not differ from that in the control groups. The same pattern was seen for IgA-containing immunoblasts. There was no difference in IgG (overall, 214 +/- 13 cells/10(6) lymphocytes) and IgM (overall, 61 +/- 10 cells/10(6) lymphocytes) spot-forming cell numbers between the five groups of individuals tested, suggesting that the anomaly noted in IgAN patients was not related to technical problems and that this could be a new feature of this renal disease. The normal levels of spontaneously activated peripheral IgA-producing cells found in transplanted IgAN patients suggest that immunosuppressive treatments could interfere with the anomalies of IgA metabolism in this disease.

Adult↗
PubMed1997

Stable expression of recombinant AMPA receptor subunits: binding affinities and effects of allosteric modulators.

Homomeric AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type glutamate receptors (GluRs) were stably expressed in kidney cells from cDNAs encoding GluR1 flop, GluR2 flip, GluR2 flop, and GluR3 flop subunits. The recombinant receptors were of the expected size and showed functional properties in whole-cell recording as previously reported. [3H]AMPA binding to all subunits was increased to a similar extent by the chaotropic ion thiocyanate (SCN-). Significant differences were found in the Scatchard plots, however, which were linear and of high affinity for GluR1 and -3 receptors (K(D) values of 33 and 52 nM, respectively) but showed curvature for GluR2 receptors, indicating the presence of two components with distinct affinities. As with brain AMPA receptors, solubilization of GluR2 receptors reduced the number of lower-affinity sites and correspondingly increased the number of higher-affinity sites. The sulfhydryl reagent p-chloromercuriphenylsulfonic acid, which increases binding to brain receptors, produced only minor changes except in the case of GluR2 flip. These results indicate that GluR2, among the subunits examined here, most closely resembles the native AMPA receptors in brain membranes. [3H]AMPA binding was inhibited in a noncompetitive manner by two drugs that change the desensitization kinetics of the AMPA receptor. In agreement with physiological observations, the apparent affinity of cyclothiazide for GluR2 flip (EC50 = 7 microM) was higher than that for receptors made of flop subunits (49-130 microM). In contrast, BDP-37, a member of the benzamide family of drugs, exhibited a lower potency for GluR2 flip (58 microM) than for any of the flop isoforms (18-40 microM). These results predict that the action of centrally active AMPA-receptor modulators varies across brain regions depending on their flip/flop composition.

Allosteric Regulation↗
PubMed1997

[Morphology and contrast enhancement of ductal carcinoma in situ in dynamic 1.0 T MR mammography].

PURPOSE: The detectability with magnetic resonance mammography (MR-M) of non-invasive ductal carcinoma in situ (DCIS), its morphology, and patterns of contrast enhancement were studied. MATERIAL AND METHODS: A total of 849 MR-M examinations were performed in 741 patients using a dynamic, contrast-enhanced FLASH 3D sequence at 1.0 T. Surgical breast biopsies were obtained in 332 cases. Histological work-up confirmed 164 carcinomas, including 20 DCIS. RESULTS: Of 20 DCIS, 14 were correctly diagnosed by MR-M on the basis of focal increase of signal intensity. In two cases (10%), no increase of signal intensity was observed. In another three cases (15%), multifocal enhancement lead to a false-negative diagnosis. In one case (5%), DCIS was a random finding in a patient diagnosed and treated for adjacent phylloides tumour. The sensitivity of MR-M was 70%. 4 (20%) of the DCIS did not show microcalcifications at conventional mammography and were only detected at MR-M. The sensitivity of conventional mammography also amounted to 70%. However, the combination of both imaging methods increased sensitivity to 90%. CONCLUSION: Ductal carcinoma in situ is not reliably detectable by MR-mammography alone due to lack of a uniform pattern of enhancement.

Biopsy↗
PubMed1997

Toxoplasmosis in kidney transplant recipients: report of six cases and review.

Six patients with toxoplasmosis complicating renal transplantation are described, and 25 other reported cases are reviewed. The mean age of the 31 patients was 35.16 years. Most of the recipients (25 of 29) showed signs of toxoplasmosis within 3 months post-transplantation, with fever, neurological disturbances, and pneumonia as the main clinical features. Diagnosis was established at autopsy in 15 cases, by serology in 13 cases, and by direct examination, culture, or polymerase chain reaction of biological samples in 5 cases. Seventeen patients also had concomitant infections. The donor was the likely source of transmission to 10 recipients; reactivation was suspected in two cases. The source of transmission could not be determined for the remaining 19 patients. The mortality rate was 64.5%. Ten of the 11 patients given specific treatment survived, indicating that early diagnosis and therapy are essential.

Adult↗
PubMed1997

Serum anti-rabbit and anti-horse IgG, IgA, and IgM in kidney transplant recipients.

BACKGROUND: The therapeutic efficacy of horse antilymphocyte globulins (ALG) or of rabbit antithymocyte globulins (ATG), used for both the prevention and treatment of allograft rejection has been well documented. However, clinical use of these heterologous antibodies can result in the production of antibodies against horse or rabbit proteins and in the development of serum sickness via circulating immune complexes. METHODS: We studied the production of human IgG, and IgM anti-rabbit and anti-horse globulins, in 240 serum samples from 111 kidney transplant recipients, of whom 89 were treated with ALG or ATG (Mérieux-France) as prophylaxis. RESULTS: Up to 8.9% of the patients had anti-ALG and/or -ATG antibodies before the first transplantation. This proportion increased significantly after. Preimmunization did not appear to be predictive of the occurrence of clinical serum sickness, yet sensitization increased, after transplantation, in up to 71% of the subjects who developed this disorder (P = 0.02). In patients receiving a second transplant, pretransplantation antibody levels were not modified by the immunosuppressive therapy applied. No relationship was found between early rejection and antiglobulin antibodies. CONCLUSIONS: Serum anti-rabbit and/or -horse antibodies were demonstrated in a significant proportion of kidney recipients, even before transplantation, possibly due to environmental exposure. A classical pattern of IgM increase was observed when the patients developed an immune response to ALG or ATG, and an IgA response after ALG. These results suggest that patients receiving ALG/ATG should be monitored for the production of anti-ALG/ATG immunoglobulins.

Adult↗
PubMed1997

IgA nephropathy: prognostic classification of end-stage renal failure. L'Association des Néphrologues de l'Est.

BACKGROUND: As yet, no clinical or morphological prognostic classification of IgA nephropathy (IgAN) has been generally accepted. The objective of our study was to quantify the risk of developing end-stage renal failure (ESRF) in IgAN. METHODS: We report a prospective longitudinal study of 210 patients with IgAN confirmed by biopsy between 1987 and 1991. Thirty-two (15.2%) patients were lost to follow-up. Mean follow-up after renal biopsy was 5.6 (SD = 2.6) years. The variables included age, gender, illnesses prior to discovery of IgAN, clinical features at IgAN discovery, 24-h proteinuria, serum creatinine, IgA level, and antihypertensive drugs taken at the time of renal biopsy. Sixty-six renal biopsies were classified by light-microscopy according to Lee's morphological classification. The end-point was ESRF. Survival was analysed by a backward and forward stepwise procedure using the Cox model. The most accurate determination of relative risk was obtained by assessing collinearity of the variables. RESULTS: Thirty-three patients (15.7%) (31 men) developed ESRF. The five univariately significant variables: gender, gross haematuria, 24-h proteinuria (24-P), serum creatinine (SC), and antihypertensive treatment, were candidates for multivariate analysis. The final model used SC (< or = 100, 100-150, > 150 mumol/l), 24-P (< 1, > or = 1 g/day) and gender (female vs male) as independent variables (relative risk and 95% confidence interval were 3.5 (2.1, 5.9) for SC; 5.1 (1.9, 13.6) for 24-P; and 3.5 (0.9, 15) for gender). These estimates were used to construct a prognostic classification of ERSF for men with IgAN: stage 1 (SC < or = 150 mumol/l and 24-P < 1 g/day), stage 2 ((SC > 150 mumol/l and 24-P < 1 g/day) or (SC < or = 150 mumol/l and 24-P > or = 1 g/day)); stage 3 (SC > 150 mumol/l and 24-P > or = 1 g/day). The ESRF-free survival was estimated with Kaplan-Meier analysis. It was 98.5% for stage 1, 86.6% for stage 2, 21.3% for stage 3 (P < 0.001), 7 years after histological diagnosis. The validity of Lee's prognostic classification was confirmed using an independent sample. CONCLUSIONS: These classifications identify groups at high risk of ESRF. Therapeutic studies should focus on these groups.

Adult↗
PubMed1997

Maintaining a hip registry for 25 years. Mayo Clinic experience.

A computerized database was established for all total joint replacements done at the authors' institution. To date the registry contains information on more than 56,000 arthroplasties of which more than 30,000 involve the hip. The registry was designed to determine the effectiveness of total hip arthroplasty as a function of implant design, surgical technique, and patient selection. Furthermore, by maintaining and updating the patient record, data regarding success or anticipated failure could be communicated to the patient. Finally, this resource would provide reliable information that could be communicated to the orthopedic community. Patients are routinely evaluated at 1, 2, and 5 years postoperatively and at 5-year intervals thereafter by examination or letter or telephone questionnaire. Followup of patients at each interval is approximately 95%. Patients are more likely to respond by questionnaire (rather than be seen in person) if they are older, if a longer time has elapsed since surgery, or if they live a long distance from the clinic. Data are collected by five full time employees including computer and statistical support specifically assigned to the project. The annual joint registry budget is in excess of $400,000. Unfortunately, the future of this endeavor is challenged by the needs to: (1) show cost effectiveness of the activity; (2) update and validate outcomes instruments used as input into the database; and (3) maintain satisfactory followup rates in a medical economic environment that often discourages patient return visits or local assessment.

Adult↗