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H W Schroeder

Publications and source records attributed to H W Schroeder.

At least 19 recordsLinked to original sources
PubMed1999

IgM heavy chain complementarity-determining region 3 diversity is constrained by genetic and somatic mechanisms until two months after birth.

Due to the greater range of lengths available to the third complementarity determining region of the heavy chain (HCDR3), the Ab repertoire of normal adults includes larger Ag binding site structures than those seen in first and second trimester fetal tissues. Transition to a steady state range of HCDR3 lengths is not complete until the infant reaches 2 mo of age. Fetal constraints on length begin with a genetic predilection for use of short DH (D7-27 or DQ52) gene segments and against use of long DH (e.g., D3 or DXP) and JH (JH6) gene segments in both fetal liver and fetal bone marrow. Further control of length is achieved through DH-specific limitations in N addition, with D7-27 DJ joins including extensive N addition and D3-containing DJ joins showing a paucity of N addition. DH-specific constraints on N addition are no longer apparent in adult bone marrow. Superimposed upon these genetic mechanisms to control length is a process of somatic selection that appears to ensure expression of a restricted range of HCDR3 lengths in both fetus and adult. B cells that express Abs of an "inappropriate" length appear to be eliminated when they first display IgM on their cell surface. Control of N addition appears aberrant in X-linked agammaglobulinemia, which may exacerbate the block in B cell development seen in this disease. Restriction of the fetal repertoire appears to be an active process, forcing limits on the diversity, and hence range of Ab specificities, available to the young.

Adult↗
PubMed1998

Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors.

To better understand the stage(s) of differentiation reached by B-type chronic lymphocytic leukemia (B-CLL) cells and to gain insight into the potential role of antigenic stimulation in the development and diversification of these cells, we analyzed the rearranged VH genes expressed by 83 B-CLL cells (64 IgM+ and 19 non-IgM+). Our results confirm and extend the observations of a bias in the use of certain VH, D, and JH genes among B-CLL cells. In addition, they indicate that the VH genes of approximately 50% of the IgM+ B-CLL cells and approximately 75% of the non-IgM+ B-CLL cells can exhibit somatic mutations. The presence of mutation varies according to the VH family expressed by the B-CLL cell (VH3 expressers displaying more mutation than VH1 and VH4 expressers). In addition, the extent of mutation can be sizeable with approximately 32% of the IgM+ cases and approximately 68% of the non-IgM+ cases differing by > 5% from the most similar germline gene. Approximately 20% of the mutated VH genes display replacement mutations in a pattern consistent with antigen selection. However, CDR3 characteristics (D and JH gene use and association and HCDR3 length, composition, and charge) suggest that selection for distinct B cell receptors (BCR) occurs in many more B-CLL cells. Based on these data, we suggest three prototypic BCR, representing the VH genes most frequently encountered in our study. These data suggest that many B-CLL cells have been previously stimulated, placing them in the "experienced" or "memory" CD5(+) B cell subset.

Amino Acid Sequence↗
PubMed1998

In situ hybridization analysis of immunoglobulin heavy chain variable gene expression with family specific oligonucleotide probes.

We have developed an improved in situ hybridization (ISH) technique for the analysis of human immunoglobulin heavy chain variable (V(H)) gene family expression in suspensions of human B lymphocytes. Oligonucleotide probes specific for framework region (FR) consensus germline sequences for each of the seven human V(H) gene families were designed and hybridization conditions were developed to accommodate the greatest degree of V(H) gene variation, maximize the sensitivity of transcript detection, and assure the specificity of the technique. The hybridization parameters were rigorously characterized by Southern hybridization to a panel of 30 V(H) cDNA clones and by ISH to 17 B cell lines expressing characterized V(H) genes. Results obtained with ISH using V(H) gene family and isotype-specific gene probes correlated well with histochemical measures of Ig gene product expression. Profiles of cellular V(H) gene expression were generated for mitogen stimulated peripheral blood B lymphocytes from six normal subjects. When compared with estimates of frequency of V(H) genes in the human germline, the results were consistent with a random pattern of V(H) family utilization.

Autoradiography↗
PubMed1998

Neuroendoscopic approach to intraventricular lesions.

OBJECT: The purpose of this study was to determine the efficacy of endoscopic treatment in patients with intraventricular tumors. METHODS: A series of 30 patients with endoscopically treated intraventricular lesions is reported. The lesions included seven colloid cysts, six astrocytomas, three subependymomas, two ependymomas, and one each of the following: pineoblastoma, pineocytoma/pineoblastoma (intermediate type), epidermoid cyst, pineal cyst, medulloblastoma, arteriovenous hemangioma, cavernoma, choroid plexus papilloma, pituitary adenoma, craniopharyngioma, melanoma, and germinoma. Total tumor resections, partial resections, biopsies, stent implantations, septostomies, and third ventriculostomies were performed. In two cases (two subependymomas > 2 cm in diameter), piecemeal endoscopic resection was ineffective because of the very firm consistency of the tumors. Therefore the endoscopic procedure was discontinued and the tumors were removed microsurgically. In the remaining cases the procedures were completed as planned. Even in the presence of difficulties such as poor orientation or significant bleeding, there was no need to abandon the endoscopic procedure. A total of 28 strictly endoscopic interventions were performed, in which the average duration was 85 minutes (range 35-170 minutes). All colloid cysts and the epidermoid lesion were completely evacuated and the capsules were widely resected. Total extirpation of solid tumors was achieved in five cases, whereas most astrocytomas were partially resected. The hydrocephalus-related symptoms resolved in all of the 22 patients with cerebrospinal fluid pathway obstruction. There were no endoscopy-related deaths. In two cases, major bleeding occurred and was controlled endoscopically. The authors observed one case of meningitis, one of mutism, two of memory loss attributed to forniceal injury, one of transient trochlear palsy after a biopsy specimen of an aqueductal tumor was obtained, and one of transient confusion after a biopsy specimen of a germinoma was obtained. CONCLUSIONS: In the authors' preliminary experience, the endoscopic approach was found to be safe and effective. In this series, it was possible to achieve relief of noncommunicating hydrocephalus, tumor resections, and even complete tumor removals by using endoscopic techniques. Based on the results, the authors believe that endoscopic techniques should be considered in the treatment of selected intraventricular lesions.

Adenoma↗
PubMed1998

Susceptibility locus for IgA deficiency and common variable immunodeficiency in the HLA-DR3, -B8, -A1 haplotypes.

BACKGROUND: A common genetic basis for IgA deficiency (IgAD) and common variable immunodeficiency (CVID) is suggested by their occurrence in members of the same family and the similarity of the underlying B cell differentiation defects. An association between IgAD/CVID and HLA alleles DR3, B8, and A1 has also been documented. In a search for the gene(s) in the major histocompatibility complex (MHC) that predispose to IgAD/CVID, we analyzed the extended MHC haplotypes present in a large family with 8 affected members. MATERIALS AND METHODS: We examined the CVID proband, 72 immediate relatives, and 21 spouses, and determined their serum immunoglobulin concentrations. The MHC haplotype analysis of individual family members employed 21 allelic DNA and protein markers, including seven newly available microsatellite markers. RESULTS: Forty-one (56%) of the 73 relatives by common descent were heterozygous and nine (12%) were homozygous for a fragment or the entire extended MHC haplotype designated haplotype 1 that included HLA- DR3, -C4A-0, -B8, and -A1. The remarkable prevalence of haplotype 1 was due in part to marital introduction into the family of 11 different copies of the haplotype, eight sharing 20 identical genotype markers between HLA-DR3 and HLA-B8, and three that contained fragments of haplotype 1. CONCLUSION: Crossover events within the MHC indicated a susceptibility locus for IgAD/CVID between the class III markers D821/D823 and HLA-B8, a region populated by 21 genes that include tumor necrosis factor alpha and lymphotoxins alpha and beta. Inheritance of at least this fragment of haplotype 1 appears to be necessary for the development of IgAD/CVID in this family.

Adult↗
PubMed1998

Clonally-related immunoglobulin VH domains and nonrandom use of DH gene segments in rheumatoid arthritis synovium.

BACKGROUND: Synovia of patients with long-standing rheumatoid arthritis (RA) are typically infiltrated with B lymphocytes and plasma cells that secrete large amounts of immunoglobulin. The CDR3 of an immunoglobulin heavy chain is composed of the VH-DH-JH join, with interposed N region addition, and thus defines clonal relatedness. Furthermore, the CDR3 lies at the center of the antigen binding site, so its length and composition influence antigen binding. We sought definitive evidence of an antigen-driven B cell response (i.e., clones derived from the same VH, DH, and JH gene segments with shared somatic mutations) in RA synovial mRNA transcripts, and to characterize CDR3 intervals at the target of inflammation in this autoimmune disease. MATERIALS AND METHODS: We screened a cDNA library generated from unselected cells from the knee joint of a 62-year-old white female with long-standing RA. This technique does not have the potential bias of selecting for antibodies that express a particular reactivity such as rheumatoid factor. C gamma recombinants were sequenced and progenitor VH, DH, and JH gene segments were assigned and somatic mutations determined by comparison to germline sequences. Analyses of DH reading frame utilization and hydropathy characteristics of CDR3s were performed. RESULTS: Two of 67 recombinants were derived from the same VH (V3-11) and JH gene segments, demonstrated shared mutations, and contained nearly identical VH-DH-JH joins, including N region addition. Three other recombinants contained identical sequence throughout the variable domain. We also found preferential utilization of a limited number of VH and DH gene segments and marked preference for a DH reading frame encoding predominantly hydrophilic residues. CONCLUSIONS: Analysis of expressed heavy chain variable domains strongly supports the hypothesis that the B cell response in RA synovium is at least in part antigen driven and oligoclonal.

Amino Acid Sequence↗
PubMed1998

Enhanced expression of immunoglobulin kappa light chains with unusually long CDR3 regions in patients with rheumatoid arthritis.

OBJECTIVE: Our previous sequence analysis of immunoglobulin kappa light chains revealed that some patients with rheumatoid arthritis (RA) expressed repertoires enriched for transcripts containing unusually long CDR3 lengths of 11 amino acid codons. This was due, in part, to N region addition at the Vkappa-Jkappa joins. In this study, we analyzed a larger number of individuals to determine how often enrichment of kappa light chain repertoires for 11 amino acid CDR3 occurs in synovial lymphocytes and peripheral blood lymphocytes (PBL) of individuals with RA. METHODS: To measure length variability of kappa chain CDR3 regions, we performed a 2 stage polymerase chain reaction amplification and polyacrylamide gel electrophoresis. We sampled PBL and synovial lymphocytes of 9 patients with longstanding RA, and used PBL of 9 age and sex matched healthy individuals as controls. RESULTS: In PBL of healthy individuals, there was low level but consistent expression of kappa chains containing CDR3 with 11 amino acids. In patients, there was enhanced expression of kappa chains containing CDR3 with 11 amino acids compared to healthy individuals. This enhanced expression of kappa chains containing CDR3 of 11 amino acids was more pronounced in synovial lymphocytes compared to PBL of the same patients. CONCLUSION: These findings suggest that there is antigenic selection of B cells bearing antibodies with unusually long kappa light chain CDR3 in RA.

Adult↗
PubMed1997

Ig D(H) gene segment transcription and rearrangement before surface expression of the pan-B-cell marker CD19 in normal human bone marrow.

The onset of IgH transcription and rearrangement is a defining characteristic of the progenitor population in which B-lineage commitment occurs. These features were used to better define the earliest stage of B-cell commitment in humans and to determine if these stages differ as a function of human ontogeny. Fetal and adult bone marrow mononuclear cells were sorted into B-lineage subpopulations on the basis of surface expression of the stem cell marker CD34, the pan-B-cell marker CD19, and IgM and analyzed for transcription and rearrangement of the IgH locus. The locus was found to be transcriptionally active before surface expression of CD19, as indicated by the presence of germline I mu, C mu, and D(H)Q52 transcripts in the CD34+ CD19- subpopulation. Transcripts from IgH alleles that had undergone DJC mu rearrangements were also detected in the CD34+ CD19- subpopulation. Within this subpopulation, low levels of DXP-containing DJC mu transcripts were detected in both fetal and adult cells. Although D(H)Q52 DJC mu transcripts were abundant in fetal CD34+ CD19- cells, they were not detected in cells of the same phenotype derived from adult bone marrow. In both fetus and adult, V(H)3-and V(H)6-containing VDJC mu transcripts were detected only in the CD19+ subpopulations. These data indicate that transcription of D(H)Q52-J(H) and DXP-J(H) rearrangements differs during fetal and adult B lymphopoiesis. Moreover, in both fetus and adult, transcription of unrearranged components of the IgH locus and DJ rearrangements can proceed before the surface expression of CD19.

Adult↗
PubMed1997

VHDJH gene sequences and antigen reactivity of monoclonal antibodies produced by human B-1 cells: evidence for somatic selection.

To understand whether the distinct VHDJH gene utilization by natural polyreactive Abs reflects the developmentally restricted Ig VHDJH rearrangements putatively expressed by B-1 cells, we generated 11 (8 IgM, 1 IgG3, 2 IgA1), 7 (6 IgM, 1 IgG1), and 7 (2 IgM, 3 IgG1, 2 IgG3) mAb-producing lines using B-1a (surface CD5+, CD45RAlow), B-1b (surface CD5-, CD45RAlow, CD5 mRNA+), and B-2 (surface CD5-, CD45RAhigh, CD5 mRNA-) cells, respectively, sorted from adult human peripheral blood. Most B-1a and B-1b, but no B-2, cell-derived mAbs were polyreactive; i.e., they bound different self and foreign Ags with different affinities. B-1a and B-2 mAbs preferentially utilized VH4 (p = 0.003) and VH3 (p = 0.010) genes, respectively. All three mAb populations utilized DXP, DLR, DN DH genes, and JH6, but no mAb utilized DHQ52. There were fewer unencoded nucleotide (N) additions in the VHDJH junctions of B-1b (3.00 +/- 2.52, mean +/- SD) than of B-1a (12.45 +/- 3.93, p = 1.23 x 10(-5)) or B-2 (8.29 +/- 4.75, p = 0.020) mAbs. Partly due to the fewer N additions and a paucity of D-D fusions, the B-1b mAb CDR3s were significantly shorter than the B-1a mAb CDR3s (p = 0.013), which contained a nonrandom Tyr distribution (p = 0.003). Finally, all but two B-1 cell-derived mAbs were mutated, in a fashion similar to that of the Ag-selected B-2 mAbs. Thus, in the human adult, B-1 cells that make natural polyreactive Abs may not be representative of the predominantly B-1 developmental waves of colonization of the fetal and neonatal B cell repertoires, and are somatically selected.

Adult↗
PubMed1997

[Neuroendoscopy and endoscopic neurosurgery].

The trend in recent neurosurgery is going toward further reduction of invasiveness and avoidance of traumatization of the brain, spinal cord, and peripheral nerves to reduce the risk of neurological and mental deficit. In this way, the duration of hospital-stay and disablement can be shortened. An important "minimally invasive" technique is neuroendoscopy. The ventricular system and the subarachnoid space of the brain give suitable conditions for the use of an endoscope. Non-communicating hydrocephalus is the most frequent indication for an endoscopic approach. However, arachnoid cysts, cystic tumors, and intraventricular lesions may also effectively be treated with an endoscope. Using special instruments, laser devices, and bipolar diathermy, even highly vascularized lesions, such as cavernomas, may be completely resected. Moreover, endoscopes are used in the treatment of various spinal diseases and carpal tunnel syndrome, as well as in endoscopy-assisted microsurgery.

Brain Diseases↗
PubMed1997

Age-related changes in serum immunoglobulins in patients with familial IgA deficiency and common variable immunodeficiency (CVID).

The concentration of serum immunoglobulins in individuals with IgA deficiency (IgAD) and CVID can vary with age to have practical implications for evaluation, therapy, and genetic analysis. Most IgAD and CVID patients in our clinic population in the Southeastern United States have inherited part or all of two extended MHC haplotypes, referred to as haplotype 1 (HLA-DQB1 0201, HLA-DR3, C4B-Sf, C4A-0, G1-15, Bf-0.4, C2-a, HSP-7.5, TNF alpha-5, HLA-B8, HLA-A1) and haplotype 2 (HLA-DQB1 0201, HLA-DR-7, C4B-S, C4A-L, G11-4.5, Bf-0.6, C2-b, HSP-9, TNF alpha-9, HLA-B44, HLA-A29). In the present study, the clinic records of 68 CVID patients and 73 IgAD patients were reviewed to determine whether patients with familial or MHC-associated IgAD or CVID experience changes in serum immunoglobulin concentrations. An increase in serum immunoglobulin to the normal range was associated with clinical improvement in one patient with CVID and haplotype 2, two patients with IgAD and haplotype 2, and one IgAD patient whose haplotype was not determined. Two patients with haplotype 1 and one with haplotype 2 had a significant decline in serum immunoglobulin: one progressed from normal to IgAD associated with IgG subclass deficiencies, and two progressed from IgAD to CVID. Five of the seven patients with notable changing serum immunoglobulin levels have a family member with either IgAD or CVID. The findings suggest that familial, MHC-associated IgAD and CVID may be either progressive or reversible disorders, and emphasize the value of monitoring immunoglobulin levels in affected individuals and their family members.

Adolescent↗
PubMed1997

Endoscopic observation of a slit-valve mechanism in a suprasellar prepontine arachnoid cyst: case report.

OBJECTIVE AND IMPORTANCE: There are several theories regarding the genesis of arachnoid cysts. However, controversy continues over what mechanisms are involved in the formation of the cysts. CLINICAL PRESENTATION: A 6-year-old female patient presented with precocious puberty. The results of a neurological examination were unremarkable. Magnetic resonance imaging revealed a large suprasellar prepontine arachnoid cyst. INTERVENTION: An endoscopic ventriculocystostomy via a right frontal burr hole was performed. During inspection of the cyst, we clearly observed a slit-valve mechanism that was obviously responsible for the formation and enlargement of the cyst. The valve was formed by an arachnoid membrane surrounding the basilar artery. Synchronous with pulsation, the valve opened and closed rapidly. CONCLUSION: A slit-valve mechanism seems to be at least one factor of the genesis of suprasellar prepontine arachnoid cysts.

Arachnoid↗
PubMed1997

Infrared-based neuronavigation and cortical motor stimulation in the management of central-region tumors.

An infrared-based neuronavigation device (Surgical Microscope Navigator) integrating a pointer system with microscope guidance, is presented. We report our experience with this system in 17 patients undergoing surgery for space-occupying lesions of the central region. Cortical motor stimulation was additionally used in selected cases. The system was helpful in all operations by guiding craniotomy, corticotomy, or extent of tissue resection. Gross total tumor removal was possible in all patients but 1. Technical problems occurred in 1 case. Postoperative neurological worsening was found in 3 patients; this was reversible within a few weeks in 2 of them. In 9 cases, neuronavigation (combined with cortical stimulation, if necessary) probably prevented permanent neurological injury by exactly localizing tumors in the central area. It is concluded that neuronavigation (combined with motor cortex stimulation) may decrease neurological injury or neurosurgical invasiveness in lesions of the central region.

Astrocytoma↗
PubMed1996

The J chain gene is transcribed during B and T lymphopoiesis in humans.

In mice and chickens, J chain appears to be expressed only in activated B cells and plasma cells. In humans, studies based mainly on transformed cells suggest that J chain expression may initiate during earlier stages in B lineage differentiation. In the present study, we isolated a series of hematopoietic subpopulations from human fetal and adult tissues by immunofluorescence cell sorting and examined each subpopulation for J chain expression by reverse transcriptase-PCR. In fetal and adult bone marrow, J chain transcripts were detected at all stages of B lineage differentiation, including the progenitor (CD34+/CD19-) and pro-B (CD34+/CD19+) cell subpopulations. J chain mRNA was also detected during fetal thymocyte development: double negative (CD4-/CD8-) through single positive (CD4+ or CD8+) cell subpopulations. The J chain message was not detected in peripheral CD3+ T cells, CD14+ monocytes, and CD56+ NK cells from either fetal or adult samples. The nucleotide sequence of J chain PCR products from CD34+/CD19- bone marrow progenitors and CD4+/CD8- thymocytes proved identical to the previously reported sequence of functionally spliced J chain mRNA. These results suggest that the J chain gene is transcriptionally active during early stages of both B cell and T cell differentiation, before the expression of their respective Ag receptors.

Adult↗
PubMed1996

Endoscopic treatment of an unusual multicystic lesion of the brainstem: case report.

We report a 32-year-old woman who presented with headache, mild hemiparesis and clumsiness of the right hand. CT and MRI revealed a multicystic formation of the brainstem involving the thalamus and midbrain. We inspected the formation endoscopically and fenestrated some of the cysts. In one of the cysts we found an anomalous vascular nidus. Postoperative MRI revealed reduction of the fenestrated cysts. The patient is doing well 13 months after endoscopy and has no neurological deficit.

Adult↗