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Biomedical subjects

S Geier

Publications and source records attributed to S Geier.

At least 19 recordsLinked to original sources

Acute rejection of marrow grafts in patients transplanted from a partially mismatched related donor: clinical and immunologic characteristics.

Bone marrow transplantation (BMT) from a partially mismatched related donor (PMRD) provides a treatment option for patients lacking a matched sibling donor. T lymphocyte depletion of the graft reduces the risk of severe graft-versus-host disease, but may increase the risk of graft failure. We evaluated the pattern of acute graft rejection in eight patients receiving PMRD BMT with respect to the conditioning therapy, diagnosis, age and sex of donor and recipient, degree of HLA mismatch, and peripheral blood immunophenotype at the time of graft failure. All grafts were partially depleted of T lymphocytes. Marrow grafts infused into patients who experienced acute rejection did not differ significantly in nucleated cell dose, degree of T lymphocyte depletion, T cell dose, or CFU-GM/kg infused, from those received by 31 patients who showed durable engraftment. In three of four patients who rejected their grafts, and had sufficient peripheral blood cells for immunophenotyping, a CD3+CD8+ T lymphocyte phenotype was predominant at the time of acute rejection. In one patient rejection was associated with a predominant population of CD3+CD4+ T lymphocytes. Rejection was significantly associated with chronic myelogeneous leukemia and in patients mismatched by more than two antigens.

Adult

Rejection of kidney allografts by MHC class I-deficient mice.

To evaluate the requirement for CD8+ T cells in kidney transplant rejection, we studied class I-deficient (class I-) mice that had received vascularized renal allografts. Because of the absence of MHC class I expression, these mice are grossly deficient in CD4-CD8+ alpha beta TCR+ cells. Despite the deficiency of CD8+ T cells in naive class I- mice, kidney allografts transplanted into class I- recipients developed significant reductions in renal blood flow and glomerular filtration rate to levels comparable to allograft controls. This functional deterioration was associated with histologic changes consistent with cellular rejection. There were no significant differences in the pattern, severity, or phenotypic character of the cellular infiltrate in allografts transplanted into class I- recipients compared to controls. In fact, substantial numbers of CD8+ T cells were present in these allografts, and the intensity and pattern of anti-CD8 staining was not different from controls. Virtually all of the CD8+ cells in the kidney grafts were class I- and CD4- and co-expressed CD8 alpha and beta chains; the majority were alpha beta TCR+. The CD8+ infiltrating cells were cytotoxic to donor targets but also exhibited activity against class I+ cells bearing self-MHC. Despite the marked CD8+ T cell infiltration of grafts, CD8+ T cells could not be detected by flow cytometry in freshly isolated splenocytes from the class I- recipients of allografts. High levels of circulating anti-class I antibodies were present in the serum of class I- recipients of kidney allografts, and these antibodies had unusual specificity in that they appeared to recognize framework epitopes of MHC class I. Thus, class I- mice readily reject kidney allografts. Although the number of CD8+ alloreactive precursors is substantially reduced in class mice, and their specificities are atypical, the pattern and character of the intra-graft CD8+ cellular response is not significantly altered. Thus, factors unrelated to precursor frequency determine the dimension of the intra-graft CD8+ response. Such factors might include cellular and/or biochemical properties of microenvironment within the graft.

Animals

[HIV-1 and tears. Results of virus isolation and polymerase chain reaction (PCR)].

Beside the threat of infection via HIV-containing blood, the ophthalmologist is especially interested in the possibility of HIV infection via the tears of HIV-positive persons. In a first step, we tried to isolate HIV-1 from the peripheral blood lymphocytes (PBL) of 50 HIV-1-antibody-positive persons in different stages of disease and to detect reverse transcriptase (RT) and p24 antigen (p24-Ag) in the supernatant. Simultaneously we carried out the same tests on tears of these patients. In 10 persons tears were collected using Schirmer strips, in 40 persons by means of microcapillaries. In a second step 10 sample pairs (PBL and tears) were tested with the polymerase chain reaction to detect proviral sequences of HIV-1 (gag, pol, env). In the first step it was not possible to isolate HIV-1 from tears, nor was it possible to detect RT or p24-Ag from the supernatant. In contrast, this was successful in 32 of the 50 examined cases for the PBL. In the second step, it was possible to detect gag, pol and env in all 10 PBL samples, while gag and pol could be detected only in one tear sample and env not at all. Our results show that the tears of HIV-positive persons contain extremely low quantities of tissue-infectious units of HIV. In addition, proviral sequences seem to occur in much lower frequency in tears than in PBL. Infection with HIV via tears therefore appears very unlikely. These findings make it possible to assign tears a place in a semiquantitative ranking of different body fluids by HIV-1 concentration.

Adolescent

The gene locus of the proton-translocating NADH: ubiquinone oxidoreductase in Escherichia coli. Organization of the 14 genes and relationship between the derived proteins and subunits of mitochondrial complex I.

The gene locus nuo of the proton-translocating NADH: ubiquinone oxidoreductase in Escherichia coli was identified by means of a DNA probe made by the polymerase chain reaction. The primers used for the reaction were derived from consensus sequences of the NAD(H)-binding subunit of mitochondrial NADH: ubiquinone oxidoreductase and the NAD(+)-reducing hydrogenase of Alcaligenes eutrophus. The nuo locus lies between minutes 49.2 and 49.6 on the E. coli chromosome and contains a cluster of 14 genes. They are bordered upstream by a sequence resembling sigma 70-dependent promoters and downstream by a sequence resembling rho-independent terminators. All 14 proteins derived from the nuo-genes are related to subunits of mitochondrial NADH: ubiquinone oxidoreductase, among which all subunits presumed to bind the substrates and to harbour the redox groups are found, as well as all seven mitochondrially encoded subunits. The E. coli enzyme seems to represent the minimal form of a proton-translocating NADH: ubiquinone oxidoreductase. The gene order in the nuo locus is conserved in comparison with other bacterial genomes and the chloroplast genome of higher plants. To some extent, the gene order correlates with the topological arrangement of the encoded subunits. The conception of modular evolution of NADH: ubiquinone oxidoreductase is further supported by the arrangement of the nuo-genes.

Alcaligenes

Improved renal function in mouse kidney allografts lacking MHC class I antigens.

The immunological responses that lead to rejection of organ and tissue transplants are triggered by the recognition of proteins encoded within the MHC. The relative contributions of responses directed toward MHC class I compared with class II in the loss of functional integrity of vascularized organ grafts have been difficult to define. The recent development of technologies which allow the generation of mice in which specific genes have been altered by gene targeting offers a new approach to addressing this question. We examine here the rejection of kidney allografts from mice lacking native MHC class I Ag. These mice were obtained from embryonic stem cells in which the beta 2 microglobulin (beta 2m) gene had been disrupted by homologous recombination. We found a significant improvement in function of renal allografts from MHC class I-deficient donors compared with allografts from donors with normal MHC class I expression. Surprisingly, the improved function of the MHC class I-deficient grafts was not associated with differences in mononuclear inflammatory cell infiltration of these grafts nor in differences in alloreactive proliferative or cytotoxic T cell responses. However, we did find differences in alloantibody response between the groups. Recipients of control allografts produced antibodies against both donor MHC class I and II, whereas recipients of MHC class I-deficient grafts formed alloantibodies primarily against donor MHC class II Ag. These studies confirm that immune responses directed toward donor MHC class I alloantigens contribute to kidney transplant dysfunction in this model. Also, these findings suggest that, at least for renal transplants, genetic manipulations which reduce MHC class I expression may be effective in overcoming some of the effects of MHC incompatibility.

Animals

Jaundice secondary to hepatic artery aneurysm: radiological appearance and clinical features.

Hepatic artery aneurysm comprises only 20% of all visceral aneurysms. The classical triad of abdominal pain, hemobilia, and jaundice is seen in less than one-third of cases. Up to 60% of patients present with an abdominal catastrophe. In our case of hepatic artery aneurysm, the diagnosis was suggested by CT scan and confirmed by angiography. Its appearance is also demonstrated on sonogram and cholangiogram. To our knowledge, this is the first case to be reported where the aneurysm was demonstrated on multiple radiographic images.

Aged

Regulation of class II gene expression in a murine pre-B cell line.

Class II major histocompatibility complex (MHC) gene expression has been studied in an Abelson virus-transformed pre-B cell line R8, and its Ia-negative variant R8205. These variant cells contained barely detectable levels of RNA specific for all class II genes, including the nonpolymorphic invariant chain gene (Ii), and did not express cell surface Ia. Fusion of this murine Ia-negative cell line to the human Ia-positive Raji cell produced an interspecies hybridoma that expressed the murine Ia. These data are further evidence for the existence of trans-acting factors that can regulate class II gene expression. Furthermore, the T cell-derived lymphokine B cell stimulatory factor 1 (BSF-1) induced expression of class II genes in the R8205 cells. Exposure of R8205 cells to an antibody that has been shown to mimic BSF-1 activity on normal B cells also resulted in expression of class II genes. These data demonstrate that three distinct signals--a lymphokine, an alloantibody binding to membrane structures, and an interspecies trans-acting factor--can induce expression of class II genes.

Animals

Prolonged psychic epileptic seizures: a study of the absence status.

Long-lived epileptic seizures associated with spike-and-wave complexes are presently considered to be the absence status, i.e., the generalized nonconvulsive status. EEG radiotelemetry allowed us to record three prolonged seizures of 3 epileptic patients. Clinical manifestations included selective rather than global impairment of higher cortical functions. Clinical impairment appeared only when patients were in a state of activity and if those altered functions were used. EEG abnormalities were diffuse, but among them spike-and-wave complexes were never diffuse. It was impossible to establish close electroclinical correlation. However, the clinical and electrical evolution was roughly isomorphic, i.e., cyclic. Major clinical manifestations were associated with spikes rather than with slow waves. Lastly, patients showed common ictal psychopathological symptoms. The problem of classifying such seizures in either the generalized or partial status is discussed. The role of selective impairment of mental functions in psychopathological symptoms is also dealth with.

Adolescent

Ictal tonic postural changes and automatisms of the upper limb during epileptic parietal lobe discharges.

Tonic postural changes of the upper limb accompanied by epileptic parietal lobe discharges are not well known. The authors report 3 such cases. In the 3 patients, a total of 18 spontaneous seizures were recorded, 12 by telemetry, from either scalp electrodes or stereotactically implanted electrodes. Of these 18 seizures, 14 included tonic postural changes of the upper limb accompanied by a contralateral parietal discharge. Combining these 3 cases with the 4 such cases in the literature, the authors found that the clinical pattern consisted of a tonic postural change in one upper limb associated with automatisms of the opposite upper limb. It was also found that the same patient might have automatisms involving the upper limb in some seizures and upper limb postural changes in other seizures, both accompanied by the same electrical discharge. It is concluded that tonic postural changes and automatisms in the upper limb may be interchangeable.

Adult

The seizures of frontal lobe epilepsy. A study of clinical manifestations.

We describe ictal clinical manifestations of frontal lobe epileptic seizures in 22 patients. After examination of all ictal clinical data, 14 catergories of signs and symptoms were established. The validity of the ictal clinical data used was confirmed on the basis of 99 frontal lobe seizures recorded by tele-electroencephalogram or tele-stereo-electroencephalogram. The main conclusion is that the frontal lobe appears to be partially connected with motor acitivity.

Adolescent

Automatisms during frontal lobe epileptic seizures.

Three new cases of automatisms occurring during frontal lobe epileptic seizures are reported. If these cases are added to those already published and adequately described in the literature, a total of 12 cases is obtained. An attempt is made to elucidate the clinical characteristics of automatisms encountered during frontal lobe seizures. This kind of automatism would seem to be clinically distinguishable from other types.

Adolescent

[Behavioral manifestations induced by electric stimulation of the anterior cingulate gyrus in man].

The electrical stimulation of a restricted part of area 24 in awake man elicits important behavioral changes. The present study is dealing with 83 epileptic patients whose brain activity was recorded in SEEG conditions, with a view to possible neurosurgery. In order to determine how seizures originate and propagate, 116 multileads electrodes (65 right, 51 left) were stereotaxically inserted in the anterior part of the cingular gyrus. 521 stimulations were performed. In 362 cases, this stimulation induced a particular behaviour which was characterized by an arousal, motor activities (involving fingers and hand, mouth, legs, eyes, associated movements of hand mouth, highly integrated movements), thymic modifications and hallucinatory manifestations. Topographical organization of the effective area in the cingular gyrus and the relation between the electrical responses and stimulation parameters are studied.

Adolescent

Clinical note: clinical and tele-stereo-EEG findings in a patient with psychomotor seizures.

A patient was studied who had posttraumatic epilepsy with adversive, psychomotor, and grand mal seizures. During tele-EEG recording from depth electrodes, 4 psychomotor seizures were accompanied by discharge originating in the frontal lobe. The patient sometimes could recall his behavior and believed it to be voluntary. Amnesia was more apt to be total after the seizure than during it.

Adult