YAC transgenic mice in the study of the genetic basis of Down syndrome.
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Animals↗
Biomedical subjects
C Griffin
Publications and source records attributed to C Griffin.
DNA sequence amplification in human prostate cancer identified by chromosome microdissection: potential prognostic implications.
The primary aim of this report was to examine the significance of increased DNA sequence copy number (gene amplification) in human prostate cancers. Three methodologies (chromosome microdissection, comparative genomic hybridization, and fluorescence in situ hybridization) were combined to (a) identify a common region of gene amplification in human prostate cells and (b) evaluate in patient samples the prevalence of this genetic change in both primary and recurrent prostate samples. The results of chromosome microdissection revealed a common amplified band region (8q24.1-24. 2) in two prostate cases with cytological evidence of gene amplification (double minutes). Fluorescence in situ hybridization using the 8q microdissection probe was performed on fresh tumor touch preparations from 44 randomly selected prostatectomy specimens. Amplification of DNA sequences from 8q24 was observed in 4 (9%) of 44 cases. Four of the 44 patients in this series presented with a positive lymph node at initial diagnosis and 3 of these 4 patients showed 8q amplification. Because of this finding, comparative genomic hybridization and fluorescence in situ hybridization were performed on tumor cells from nine prostate cancer patients with recurrent disease. In eight of nine cases a gain of DNA sequences encompassing 8q24 was observed. Taken together with other evidence implicating 8q gain in prostate cancer progression, these results suggest that the analysis of this genetic change may have diagnostic utility as a marker of prostate cancer progression.
Chromosome Banding↗
Pinnal diseases.
The pinna is the most obvious part of the canine and feline ear. It is a region of the body prone to numerous skin diseases, most of which have lesions on other body areas. A small number of diseases have lesions that are usually limited to the pinna. Other diseases involve the pinna as an initial or common site of disease.
Animals↗
Partial structure and mapping of the human myelin P2 protein gene.
The myelin P2 protein, a 14,800-Da cytosolic protein found primarily in peripheral nerves, belongs to a family of fatty acid binding proteins. Although it is similar in amino acid sequence and tertiary structure to fatty acid binding proteins found in the liver, adipocytes, and intestine, its expression is limited to the nervous system. It is detected only in myelin-producing cells of the central and peripheral nervous systems, i.e., the oligodendrocytes and Schwann cells, respectively. As part of a program to understand the regulation of expression of this gene, to determine its function in myelin-producing cells, and to study its role in peripheral nerve disease, we have isolated and characterized overlapping human genomic clones encoding the P2 protein. We report here on the partial structure of this gene, and on its localization within the genome. By using a panel of human-hamster somatic cell hybrids and by in situ hybridization, we have mapped the human P2 gene to segment q21 on the long arm of chromosome 8. This result identifies the myelin P2 gene as a candidate gene for autosomal recessive Charcot-Marie-Tooth disease type 4A.
Amino Acid Sequence↗
Is ovarian cancer a clonal disease?
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Alleles↗
Structure of the human spermidine/spermine N1-acetyltransferase gene (exon/intron gene organization and localization to Xp22.1).
The super induction of spermidine/spermine N1-acetyltransferase (SSAT), has been implicated in the cytotoxic response of human solid tumors to the bis(ethyl)polyamines. The SSAT response is a phenotype specific response and is modulated at the level of increased steady-state mRNA levels and enzyme protein. The human genomic region (4,095 bases) containing the coding sequence of SSAT has been cloned and localized to the Xp22.1 region. Primer extension analysis indicates the transcription of SSAT starts 179 bases upstream from the translational start site and appears to be under the control of a "TATA-less" promoter. The availability of this human clone will facilitate the direct functional examination of the SSAT gene.
Acetyltransferases↗
Transplantation of umbilical cord blood after myeloablative therapy: analysis of engraftment.
The possibility that umbilical cord and placental blood from an HLA-identical sibling might produce stable donor-derived lymphohematopoietic engraftment was tested in a patient with juvenile chronic myelogenous leukemia (JCML). After conditioning with high-dose busulfan and cyclophosphamide, cryopreserved umbilical cord blood, containing 0.5 x 10(8) nucleated cells/kg and 2.7 x 10(4) colony forming units-granulocyte, macrophage (CFU-GM)/kg, was infused. A leukocyte count greater than 1,000/microL, absolute neutrophil count (ANC) greater than 500/microL, and platelet count greater than 20,000/microL (untransfused) were observed on days 39, 39, and 47 after transplantation, respectively. Donor cell engraftment was documented in the peripheral blood and bone marrow by cytogenetic analysis, restriction fragment length polymorphism (RFLP), and polymerase chain reaction (PCR) as early as day 21. Furthermore, the donor origin of each lymphohematopoietic lineage (ie, CD5+ T cells, CD19/20+ B cells, CFU-GM, and burst-forming unit-erythrocyte [BFU-E]) was confirmed. On day 200, assays of the peripheral blood and bone marrow showed an abnormal proliferation of CFU-GM at low seeding densities in the absence of exogenous growth factors, as well as a hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF), both pathophysiologic characteristics of JCML. Recurrent disease was confirmed histologically on day 225. Together, these results demonstrate that umbilical cord blood contains sufficient numbers of hematopoietic stem cells necessary for the engraftment of leukemia patients treated with myeloablative therapy and that the detection of "spontaneous" CFU-GM and hypersensitivity to GM-CSF after treatment is a marker of residual or recurrent disease in patients with JCML.
Base Sequence↗
Klippel-Feil syndrome.
Klippel-Feil syndrome is characterized by congenital fusion of two or more cervical vertebrae and may be associated with other organ system anomalies. Although many congenital anomalies are of little clinical importance to the emergency physician, Klippel-Feil syndrome is associated with both spontaneous and progressive neurologic sequelae as well as a predisposition for serious neurologic injury after relatively minor neck trauma. Such patterns of skeletal abnormalities as an unstable fusion pattern, craniocervical anomalies, and associated spinal stenosis are associated with a higher risk of neurologic sequelae. We report the case of a patient with a previously undiagnosed type II Klippel-Feil syndrome who presented after neck trauma to illustrate how further diagnostic imaging modalities may be required to elucidate the presence or absence of acute injury. Key considerations in the emergency management of such patients include radiographic evaluation for hypermobile cervical segments, the anticipation of difficult tracheal intubation, and proper follow-up and referral because of the associated other organ system anomalies and progression of the skeletal pathology.
Adolescent↗
Fear of a black (and working-class) planet: young women and the racialization of reproductive politics.
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Black or African American↗
Bone marrow transplantation of chronic myelogenous leukemia in chronic phase: evaluation of risks and benefits.
PURPOSE: Allogeneic bone marrow transplantation (BMT) is an option for some patients with chronic myelogenous leukemia (CML). We retrospectively evaluated the effect of various risk factors observed at diagnosis and at transplantation on survival, event-free survival (EFS), and relapse after BMT. PATIENTS AND METHODS: Seventy-nine patients with CML in chronic phase (CP) were treated with cyclophosphamide and total body irradiation followed by BMT. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine (CsA) in most instances or CsA plus the use of lymphocyte-depleted bone marrow (BM). RESULTS: Survival at 4.5 years was 52%. Stratified by age and GVHD prophylaxis, the actuarial survival was 65% (95% confidence interval [CI], 47% to 78%) in patients aged less than 30 years receiving unmanipulated BM, 33% (95% CI, 12% to 56%) in patients greater than or equal to 30 years old receiving unmanipulated BM, and 38% (95% CI, 14% to 63%) in patients greater than or equal to 30 years old receiving lymphocyte-depleted BM. In univariate analysis, patient age (greater than or equal to 30 years) and the use of lymphocyte-depleted BM negatively influenced EFS. When stratified by age and GVHD prophylaxis, however, ABO incompatibility, cytomegalovirus (CMV) seropositivity, and chronic GVHD significantly reduced the probability of EFS. Factors that have been associated with early death in nontransplanted patients (ie, sex, spleen size, blast and platelet counts at presentation) were not predictive of long-term survival outcome after BMT. CONCLUSIONS: The data suggest that (1) BMT should be offered early after diagnosis to all patients with CML in CP who have compatible sibling donors regardless of prognostic factors at presentation, (2) GVHD remains the principal cause of mortality after BMT in patients receiving CsA, and (3) T-cell depletion by the physical separation method of counterflow elutriation (CE) is associated with a significant risk of relapse.
Adolescent↗
Comparison of molecular and cytogenetic methods in the evaluation of engraftment following allogeneic bone marrow transplantation.
Cytogenetic evaluation of patients after bone marrow transplantation (BMT) has provided a standard method of documentation of hematopoietic engraftment. More recently, recombinant DNA technology has also been applied to determine engraftment status. In order to establish the relative utility of these methods in clinical practice we have directly compared the data from cytogenetic and recombinant DNA methods, evaluating engraftment status in 68 BMT recipients. Patients were evaluated pre-transplant, 30, 60, 90, and 180 days after BMT, and yearly thereafter for 1) the presence or absence of the Y chromosome in sex-mismatched allogeneic transplant recipients, 2) the presence or absence of the Philadelphia chromosome [t(9;22)] in patients transplanted for chronic myelogenous leukemia (CML), 3) restriction fragment length polymorphism (RFLP) profiles, and/or 4) clonal rearrangement of the bcr gene. Cytogenetic examination of unstimulated bone marrow and recombinant DNA tests of nucleated peripheral blood or bone marrow cells produce qualitatively similar data in the identification of patient and donor cells and/or normal and tumor cells. Differences in the results obtained by the two analytic methods were most often due to the restricted cell populations evaluable by cytogenetic studies of PHA-stimulated peripheral blood specimens. DNA analyses could frequently be applied at earlier intervals after transplantation and, in cases of graft rejection, when cell counts were low. Although recombinant DNA methods required fewer cells and demonstrated greater sensitivity in detection of minor cell populations in the majority of instances, the cytogenetic evaluation may complement the DNA studies and allow detection of additional chromosomal anomalies.
Bone Marrow Transplantation↗
Bioethics. How to manage conflicting values.
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Bioethics↗
Comparative mapping of the constitutional and tumor-associated 11;22 translocations.
The reciprocal t(11;22)(q23;q11) is the most common non-Robertsonian constitutional translocation in humans. The tumor-associated 11;22 rearrangement of Ewing sarcoma (ES) and peripheral neuroepithelioma (NE) is cytologically very similar to the 11;22 constitutional rearrangement. Using immunoglobulin light-chain constant region, ETS1 probes, and the technique of in situ hybridization, we previously were able to show that the constitutional and ES/NE breakpoints are different. As a first step toward isolating these translocation junctions and to further distinguish between them, we have made somatic cell hybrids. Cells from a constitutional 46,XX,inv(9),t(11;22) carrier and from an ES cell line with a t(11;22) were separately fused to a hypoxanthine-guanine phosphoribosyltransferase-deficient Chinese hamster cell line (RJK88). Resulting clones were screened with G-banding and Southern hybridization. Hybrid clones derived from the constitutional t(11;22) were established which contained the der(22) and both the der(22) and the der(11). Hybrid clones derived from the ES cell line containing the der(11) were isolated. Using the technique of Southern hybridization we have sublocalized the loci; ApoA1/C3, CD3D, ETS1, PBGD, THY1, D11S29, D11S34, and D11S147 to the region between the two breakpoints on chromosome 11 and V lambda I, V lambda VI, V lambda VII, and D22S10 to the region between the breakpoints on chromosome 22. Using anonymous DNA probes, we found that D22S9 and D22S24 map proximal to the constitutional breakpoint and that D22S15 and D22S32 map distal to the ES breakpoint on chromosome 22.
Animals↗
Structural and functional analysis of a growth-regulated gene, the human calcyclin.
Calcyclin was originally defined as a cDNA clone (2A9) whose cognate RNA is growth-regulated and whose sequence shows strong similarities to the sequences of the S-100 protein, a calcium-binding protein, as well as to a subunit of the major cellular substrate for tyrosine kinase. Using the full-length cDNA, we have now isolated from a human genomic library several phages containing calcyclin sequences. One of the phages, ch. 28-10, contains the entire calcyclin gene, plus extensive flanking sequences. The calcyclin gene is a unique copy gene and has 3 exons. The 5' flanking sequence has been characterized, both structurally and functionally. Besides a TATA box, it contains, in the region proximate to the cap site, GC boxes and a sequence with a strong homology to the enhancer core of the SV40 promoter. Other enhancer-like elements are found scattered in both the 5' and 3' flanking regions. The proximate 5' flanking region is very active in driving the transient expression of linked reporters in transfection experiments. Finally, the calcyclin gene has been localized to the long arm of human chromosome 1, near the ski oncogene.
Base Sequence↗
Magnetic resonance appearance of slow flow vascular malformations of the brainstem.
Twelve patients with slow flow brain stem vascular malformations had magnetic resonance scans performed on a 1.5 Tesla scanner using T1 (TR = 400-800 ms, TE = 25 ms) and T2 (TR = 2000 ms, TE = 20, 25, 80 ms) weighted scans. Eight patients (70%) had solitary brainstem vascular malformations while 4 (30%) had multiple lesions both supra and infratentorially. Five patients had venous angiomas demonstrated by angiography and MR. There were 26 lesions seen on MR of which only 14 were identified by CT. These lesions demonstrated a specific MR image pattern indicative of subacute or chronic parenchymal hematoma. It was characterized by an iso to hyperintense central signal surrounded by a well defined thin band of low signal intensity. The central zone could appear to be single or multilocular. In multilocular lesions the hemorrhages within different cells could be of different ages. One patient did not have findings of a chronic hematoma but exhibited only low signal secondary to calcification and a venous angioma. None of these lesions had surrounding edema. Despite the variable etiologies of slow flow vascular malformations of the brainstem, their MRI manifestations seem to indicate a final common pathway of chronic hematoma. These lesions are quite distinct from MS or tumor, the usual clinical considerations in the differential diagnosis.
Adolescent↗
Postthyroidectomy respiratory distress.
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Airway Obstruction↗
Use of cerebrospinal fluid gating to improve T2-weighted images. Part II. Temporal lobes, basal ganglia, and brain stem.
Ungated and gated magnetic resonance images of the temporal lobes, basal ganglia, and brain stem acquired with the use of long repetition times (TRs) and long echo-delay times (TEs), were compared quantitatively. Twenty-five pairs of images obtained on a 1.5-T system were evaluated. Ungated images (TR = 2,000 msec, TE = 80 msec) were acquired in the same manner as gated images except for TR, which, for gated studies, was determined by a patient's heart rate and generally fell into the 1,500-1,800-msec range. Three image parameters were assessed: signal-to-noise ratio (S/N), object contrast, and resolving power. In both normal and abnormal brain tissue, gated images were superior to ungated images in object contrast and resolving power and equivalent in S/N. More so than in comparable studies of the spinal cord, ungated studies were susceptible to both false-positive and false-negative interpretations. As in spinal cord studies, the major benefit of gating was the elimination of phase shift images arising from basal cisterns and the third ventricle.
Basal Ganglia↗
Potential false-negative MR images of the thoracic spine in disk disease with switching of phase- and frequency-encoding gradients.
Two patients with thoracic disk protrusion were evaluated with magnetic resonance imaging. A T1-weighted spin-echo sequence was used, with and without switching of the phase- and frequency-encoding gradients. Both disks were well delineated when the frequency-encoding gradient was parallel to the spinal axis. When the gradients were switched (with the phase-encoding gradient parallel to the spinal axis), both herniated disks were partially obscured by a posteriorly displaced fat signal from marrow, caused by a chemical shift artifact. In addition, the anterior subarachnoid space appeared falsely narrowed, and the cerebrospinal fluid (CSF) signal intensity was increased, which reduced the CSF-cord contrast. These findings suggest that switching the orientation of the frequency- and phase-encoding gradients may result in false-negative T1-weighted sagittal images of the thoracic spine.
Adult↗