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Biomedical subjects

C Griffin

Publications and source records attributed to C Griffin.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1989

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

Growth factor requirements of childhood acute leukemia: establishment of GM-CSF-dependent cell lines.

Eight permanent cell lines were established from cells of 50 consecutive patients with childhood acute leukemia. Three cell lines required growth factor-containing conditioned media. Analysis using blocking antisera and recombinant granulocytic macrophage (GM) colony-stimulating factor (CSF) identified GM-CSF as a growth factor required to establish the latter three cell lines and necessary for their continuous proliferation in chemically defined medium. Two of the GM-CSF-dependent cell lines were derived from patients with undifferentiated T- and a biphenotypic B-myelomonocytic leukemia, which suggests that GM-CSF might maintain proliferation of leukemias originating from immature progenitor cells. Cytogenetic analysis indicated that all established leukemic cell lines were aneuploid, with six lines containing chromosomal alterations related to those observed in the leukemic cells of the patient. Two patients did not have an abnormal clone identified in the marrow but did yield an aneuploid cell line. These studies indicate that GM-CSF-dependent leukemic cell lines can be established in a fraction of childhood leukemia. These cell lines lend themselves to studies aimed at the evaluation in vitro of the role of growth factors in controlling proliferation and differentiation of leukemic cells.

Acute Disease↗
PubMed1986

A novel glycoprotein for detection of herpes simplex virus type 1-specific antibodies.

A novel herpes simplex virus type 1 (HSV-1)-specific glycoprotein reactive with monoclonal antibody H1379 was purified by affinity chromatography. This glycoprotein, provisionally designated as gG-1, forms two sets of bands with molecular weights of 40-44,000 and 60-88,000. When used in an immunodot enzymatic assay, gG-1 reacted strongly with rabbit antisera to HSV-1, but not with sera hyperimmune to HSV-2. Specificity of the assay was further established by the lack of reactivity of convalescent sera collected from 20 patients with primary genital HSV-2 infections, and from 100 sero-negative individuals. In contrast, antibodies to gG-1 were detected in 9 of 10 patients with primary HSV-1 infection, and in 63/67 patients with culture-positive, recurrent oral or genital HSV-1 infection. Reproducibility of the gG-1 immunodot assay for HSV-1 antibody detection was 96%. Serological assay with purified gG-1, done in parallel with the assay using purified gG-2 described in an earlier report, provides simple and reliable methods to detect type-specific HSV-1 and HSV-2 antibodies for seroepidemiological studies.

Animals↗
PubMed1986

Adaptation of a commercially available indirect fluorescent antibody slide test for measuring measles-specific immunoglobulins.

A commercially available indirect fluorescent antibody (IFA) test was evaluated for the determination of measles-specific immunoglobulins G and M (MIgG, MIgM). The IFA test detected fourfold rises of MIgG in 34 of 35 (97%) cases of measles confirmed by complement fixation or hemagglutination inhibition. In determining immune status, MIgG-IFA correlated with hemagglutination inhibition in 22 of 23 (96%) cases. The IFA test detected MIgM in only 11 of 34 acute-phase sera collected within 5 days of the reported onset of rash and in the convalescent specimens of another 13 of the 35 specimens. The IFA test is an effective method for the conventional diagnosis of measles and for determining immune status. This IFA test has a limited role as a rapid diagnostic test for measles when used to detect measles-specific MIgM in acute-phase sera obtained from patients with suspected measles.

Agglutination Tests↗
PubMed1986

Neurologic complications in oral polio vaccine recipients.

Between April 1982 and June 1983 four children 3 to 24 months of age were referred for evaluation of neurologic abnormalities found to be compatible with vaccine-related poliovirus infection, which had not been suspected by referring physicians. Patients were epidemiologically unrelated residents of Indiana, and none had prior symptoms suggestive of immunodeficiency. All had received poliovirus vaccine orally (first dose in three, fourth dose in one) and a diphtheria-tetanus-pertussis injection in the left anterior thigh within 30 days of symptoms. A vaccine-like strain of poliovirus was isolated from each patient, and each had symptoms (left leg paralysis in three; developmental regression, spasticity, and progressive fatal cerebral atrophy in one) persisting for at least 6 months. Immune function was normal in two with poliovirus type 3 infection, and abnormal (hypogammaglobulinemia, combined immunodeficiency) in two with type 1 and type 2 infection, respectively. The incidence of observed vaccine-related poliovirus infection in Indiana recipients of orally administered poliovirus vaccine was 0.058 per 100,000 per year, significantly greater (P less than 0.001) than predicted.

Atrophy↗
PubMed1986

Hydrochlorothiazide-induced thrombocytopenic purpura.

A case of thrombocytopenic purpura caused by hydrochlorothiazide is reported. A 65-year-old man received hydrochlorothiazide 50 mg/d to control his mild hypertension. Approximately one year after initiation of therapy, the patient developed epistaxis and generalized malaise with anorexia. A peripheral blood smear showed a reduction in platelets. The drug was discontinued; two weeks later the patient's symptoms resolved completely and his platelet count returned to normal. The results of several experiments suggest a mechanism of sensitivity, i.e., an antigen-antibody type of reaction. Hydrochlorothiazide therapy should be stopped if thrombocytopenic purpura develops. If recognized early, the symptoms will resolve spontaneously. The use of corticosteroids may aid in shortening the duration of thrombocytopenia.

Aged↗