Smcx lies distal to DXHX674 and DXHX679 on the mouse X chromosome.
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Animals↗
Biomedical subjects
M J Mitchell
Publications and source records attributed to M J Mitchell.
Encyclopedia of the mouse genome V. Mouse Y chromosome.
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Animals↗
Identification of a mouse male-specific transplantation antigen, H-Y.
The male-specific transplantation antigen, H-Y, causes rejection of male tissue grafts by genotypically identical female mice and contributes to the rejection of human leukocyte antigen-matched male organ grafts by human females. Although first recognized 40 years ago, the identity of H-Y has remained elusive. T cells detect several distinct H-Y epitopes, and these are probably peptides, derived from intracellular proteins, that are presented at the cell surface with major histocompatibility complex (MHC) molecules. In the mouse, the gene(s) controlling H-Y expression (Hya) are located on the short arm of the Y chromosome between the zinc-finger genes Zfy-1 and Zfy-2. We have recently identified Smcy, a ubiquitously expressed gene, in this region and its X-chromosome homologue, Smcx. Here we report that Smcy encodes an H-YKk epitope that is defined by the octamer peptide TENSGKDI: no similar peptide is found in Smcx. These findings provide a genetic basis for the antigenic difference between males and females that contributes towards a tissue transplant rejection response.
Amino Acid Sequence↗
Localization of specific joint causing hindfoot pain: value of injecting local anesthetics into individual joints during arthrography.
OBJECTIVE: The purpose of this study was to evaluate the utility of selective injection of local anesthetic into hindfoot articulations for localizing the source of posttraumatic pain and to compare clinical response with the severity of degenerative change in the various articulations evident on plain radiographs or CT scans. SUBJECTS AND METHODS: Anesthetic arthrography was performed in 18 patients with posttraumatic hindfoot pain. In all, 32 joints were assessed: 15 talocalcaneonavicular, 11 subtalar, five ankle, and one calcaneocuboid. Following intraarticular injection of a mixture of equal amounts of meglumine diatrizoate 60%, lidocaine 1%, and bupivacaine 0.25%, patients were asked to grade the degree of pain relief they experienced on a scale from 0% to 100%. The degree of degenerative changes seen on preliminary radiographs and CT scans was graded blindly and retrospectively by an experienced musculoskeletal radiologist using a 3-point scale (grade 0 indicated a normal joint, grade 1 indicated mild to moderate degenerative change, and grade 2 indicated severe degenerative change). The value of findings on both routine radiographs and CT scans as predictors of the degree of symptomatic relief obtained from specific joint injections was determined. Arthrodesis was performed in nine patients on the basis of the results of anesthetic injections. RESULTS: The degree of pain relief experienced after intraarticular injection of anesthetic correlated with the severity of degenerative change as assessed by routine radiography in 15 of 32 joints and as assessed by CT in eight of 18 joints. In 14 of 32 joints assessed by routine radiography and in seven of 18 joints assessed by CT, the amount of pain relief achieved by anesthetic arthrography was less than that predicted by imaging evidence of degenerative disease. In five of 32 joints judged normal on plain film radiographs, significant pain relief was experienced following anesthetic injection, resulting in a change in the proposed surgical procedure. Long-term follow-up indicated satisfactory results in eight of the nine patients in whom arthrodesis was performed. CONCLUSION: Selective intraarticular anesthetic injections afford a direct method of confirming the site of hindfoot pain and may aid in surgical planning, because plain film radiography or CT may underestimate or poorly indicate the most symptomatic articulations.
Adult↗
Deletion mapping by immunoselection against the H-Y histocompatibility antigen further resolves the Sxra region of the mouse Y chromosome and reveals complexity of the Hya locus.
A genetic map of the mammalian Y chromosome cannot be produced by standard Mendelian methods because the Y does not participate in meiotic exchange over the majority of its length. However, deletion mapping of the mouse Y chromosome is facilitated by the fact that its short arm carries the histocompatibility-Y (Hya) locus. This locus encodes male-specific (H-Y) antigens that can be selected against in tissue culture by the technique of immunoselection. To produce cells carrying deletions, cytotoxic T lymphocytes (CTLs) specific for H-Y antigens were cocultured with a lymphoblastoid cell line derived from a mouse carrying the portion of the short arm defined by the Sxra translocation on the distal end of its X chromosome. H-Y antigen-loss variant cells that contained Y-specific deletions were identified. Molecular, karyotypic, and immunological analysis of the deletion variants allowed us to define up to 16 ordered intervals and suggested an overall organization of Sxra. The analysis also suggests that at least two and up to five distinct loci encode H-Y antigens.
Animals↗
A mouse Y chromosome gene encoded by a region essential for spermatogenesis and expression of male-specific minor histocompatibility antigens.
A new mouse Y chromosome gene, Smcy, has been isolated from the region encoding Spy, a spermatogenesis gene and Hya and Sdma, the genes that, respectively, control the expression of the male specific minor histocompatibility antigen H-Y, as measured by specific T-cell assays and the serologically detected male antigen SDMA. Smcy is well conserved on the Y in mouse, man and even marsupials. It is expressed in all adult male tissues tested and can also be detected during mouse development from as early as two cells. In addition, its human Y homologue, SMCY, is expressed in multiple tissues and maps to the same Yq deletion interval as the human H-Y antigen controlling locus, HY.
Amino Acid Sequence↗
A novel X gene with a widely transcribed Y-linked homologue escapes X-inactivation in mouse and human.
A new gene, designated Smcx, was cloned from the mouse X chromosome by its homology to the Y located gene Smcy. Using direct in situ hybridisation Smcx was mapped to the distal end of the mouse X chromosome (XF2-XF4) and its human homologue, SMCX, was mapped to proximal Xp (Xp11.1-Xp11.2). Further meiotic mapping in the mouse placed Smcx in the Plp-Pdha1 interval. As Smcx/SMCX have widely expressed homologues on the Y chromosome, they appeared good candidates for genes that escape X-inactivation. In the human we show this to be the case as SMCX is expressed in hamster-human hybrids containing either an active or inactive human X chromosome. Two alleles of Smcx were found to be expressed in T(16;X)16H female mice despite the intact X chromosome being inactive in all cells. This indicates that Smcx is also not subject to X-inactivation and provides the first example of a gene that is expressed from inactive and active X chromosomes in the mouse.
Alleles↗
A huge osteophyte in the sacroiliac joint: appearance on bone SPECT.
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Bone Neoplasms↗
Early recognition of sacroiliitis by magnetic resonance imaging and single photon emission computed tomography.
OBJECTIVE: To evaluate the role of magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) in the detection of sacroiliitis in patients with clinical features of inflammatory back disease but without conventional radiographic changes. METHODS: Twenty-four patients with inflammatory low back pain (ILBP) and normal or suspicious changes of sacroiliitis (New York criteria: 0-1) on conventional radiography, in addition to 12 control subjects were studied. MRI, bone and SPECT scans of the sacroiliac (SI) joints were obtained and interpreted without knowledge of patient identification. MRI scans were scored according to the modified New York criteria and examined for the presence of joint fluid, abnormalities in articular cartilage and in the underlying marrow signal. A quantitative and qualitative assessment of radiopharmaceutical uptake in the SI joints was derived from planar bone scan films and SPECT scans. RESULTS: MRI detected features of scaroiliitis in 54% of patients with ILBP and in 17% of controls (p = 0.07). Quantitative and qualitative analysis of planar bone scan films did not reveal any differences between the 2 patient groups. In contrast, SPECT scanning identified sacroiliitis in 38% of patients with ILBP compared to none in controls (p = 0.05). When MRI and SPECT scanning were combined there was evidence of sacroiliitis in 63% of patients with ILBP and in 17% of controls (p = 0.025). CONCLUSION: MRI and SPECT bone scanning provide objective and complementary evidence of sacroiliitis in patients with clinical features of inflammatory spinal disease in the absence of conventional radiographic changes.
Adult↗
Assessment of painful late effects of lumbar spinal fusion with SPECT.
UNLABELLED: The authors reviewed planar, SPECT and other contemporaneous radiologic images of the spine and the medical records of 33 patients with back pain after lumbar fusion surgery in order to determine the value of SPECT in the assessment of painful late effects of spinal fusion surgery. METHODS: Twenty-one patients had lateral fusion, nine patients had posterior fusion only and three patients had anterior and posterior fusions. There were 24 patients who had surgery more than 4 yr ago (late group, mean 11.8 yr) and 9 patients who had surgery less than 4 yr ago (early group, mean 17.8 mo). RESULTS: The most common SPECT abnormality in patients in the late group were lesions in the vertebral bodies and apophyseal joints in the free motion segments adjacent to the fused segments (62.5% of patients). Such lesions occurred in 46% of patients after lateral fusion, in 87.5% of patients after posterior fusion and in 67% of patients after posterior and anterior fusions. No SPECT abnormalities were detected in the fused segments in patients in the late group with solid lateral fusion but were detected in three patients with solid posterior fusion. These results correlate with biomechanical studies that have shown posterior fusion to produce the largest amount and lateral fusion to produce the least amount of stress in the free segments adjacent to the fusion. Lateral fusion was found to have a more stabilizing effect than posterior fusion. CONCLUSION: In addition to the already established value of SPECT in detecting painful pseudoarthrosis, our results indicate that SPECT is of value in the assessment of painful late effects of fusion.
Adult↗
Effects of plant flavonoids and other allelochemicals on insect cytochrome P-450 dependent steroid hydroxylase activity.
The plant flavonoids flavone, chrysin, apigenin, kaempferol, morin, quercetin, myricetin and phloretin were found to inhibit in a dose-dependent manner the cytochrome P-450 dependent ecdysone 20-monooxygenase activity associated with adult female Aedes aegypti, wandering stage larvae of Drosophila melanogaster, and fat body and midgut from prewandering and wandering stage last instar larvae of Manduca sexta. The concentrations of these flavonoids required to elicit a 50% inhibition of the steroid hydroxylase activity in all the insects ranged from ca 1 x 10(-5) to 1 x 10(-3) M. In addition, lower concentrations (1 x 10(-6) to 1 x 10(-5) M) of the flavonols kaempferol, morin, quercetin and myricetin significantly stimulated (50-100% above control) M. sexta fat body ecdysone 20-monooxygenase activity. Other plant allelochemicals examined and found to significantly inhibit insect ecdysone 20-monooxygenase activity include corynanthine, quinidine, and quinine; whereas, indican and mimosine were found to significantly stimulate M. sexta fat body steroid hydroxylase activity. Several allelochemicals were without effect at all concentrations tested. Although none of the compounds tested in this study elicited effects at very low concentrations (1 x 10(-9) to 1 x 10(-8) M), the in vitro monooxygenase radioassay does hold considerable promise as a screening tool for the detection and identification of plant allelochemicals which may function as biopesticides affecting insect ecdysteroidogenesis.
Aedes↗
Role of SPECT in differentiating malignant from benign lesions in the lower thoracic and lumbar vertebrae.
The authors categorized 125 spinal lesions in cancer patients and 127 lesions in patients with back pain according to their location in the vertebra on single photon emission computed tomographic (SPECT) images. Forty-four lesions were metastases, all in patients with known malignancy. Lesions in the apophyseal joints were all benign. Lesions manifesting as abnormal uptake projecting beyond the vertebral body surface were osteophytes. Thirty-seven percent of the lesions detected in cancer patients were categorized in either of these two benign categories. Lesions showing focal or diffuse uptake in the body were usually benign (96% and 87%, respectively). Lesions showing uptake in the body and pedicle were usually metastases (83%). When abnormal uptake was seen in both the body and posterior elements but with an intervening normal pedicle, benign disease was the most common cause (93%). It was concluded that the location of lesions on tomographic images provides useful information for differentiation between malignant and benign lesions in the vertebrae.
Diagnosis, Differential↗
Single photon emission computed tomography in the diagnosis of inflammatory spondyloarthropathies.
OBJECTIVE: The role of bone scintigraphy in the evaluation of patients with inflammatory spondyloarthropathy is controversial and previous studies have reported a lack of sensitivity and specificity. The aim of our study was to determine whether single photon emission computed tomography (SPECT) scanning would enhance the clinical utility of bone scintigraphy in the detection of inflammatory axial disease, in particular sacroiliitis. METHODS: Twenty patients with definite sacroiliitis (New York criteria > 1) on plain film radiographs and 20 age matched controls were studied. Bone scintigraphy and SPECT scanning were carried out 2 h after an intravenous injection of 99mTc imidodiphosphonate (IDP). A quantitative and qualitative assessment of radiopharmaceutical uptake in the sacroiliac (SI) joints was derived from planar films and a qualitative analysis of uptake in the SI joints was derived from SPECT scans. All films were read without knowledge of patient identification. RESULTS: Quantitative analysis of planar films did not identify any difference between study and control groups (p > 0.05). Qualitative assessment of planar films identified features of sacroiliitis more frequently in patients than in controls (p < 0.05) with a sensitivity of 25% and a specificity of 95%. SPECT scanning also revealed enhanced radiopharmaceutical uptake in the SI joints more frequently in patients than in controls (p < 0.001) with a sensitivity of 85% and a specificity of 90%. Increased uptake in the lumbar facet joints and costovertebral joints was identified in 3 patients. Similar abnormalities were not detected in the control group. CONCLUSION: Our results indicate that SPECT scanning is both sensitive and specific for the detection of established sacroiliitis and may also identify inflammatory disease at other sites in the spine.
Adult↗
Marsupial Y chromosome encodes a homologue of the mouse Y-linked candidate spermatogenesis gene Ube1y.
The mammalian subclass Theria consists of infraclasses Metatheria (marsupials) and Eutheria ('placentals') which diverged from each other 120-150 million years before present (Myr BP). Both infraclasses have Y chromosome-dependent testis determination but direct molecular evidence linking the Metatherian and Eutherian Y chromosomes is lacking. Comparative analyses indicate that three mammalian genes have remained Y-linked for at least 80 Myr, since the divergence of the Eutherian orders from a common ancestor. These are Zfy, a gene encoding a transcription factor of the zinc-finger type; Sry, the putative primary testis-determining gene; and Ube1y (formerly Sby or A1s9Y-1), a candidate for the mouse spermatogenesis gene Spy, encoding a ubiquitin-activating enzyme E1 homologue. Although in marspials Zfy homologues are autosomal, a Y homologue of Sry has recently been isolated. We report here the identification of a functional marsupial Y-linked homologue of the murine Ube1y gene establishing that Metatherian and Eutherian Y chromosomes diverged from a common ancestor. This extreme conservation indicates that Ube1y plays a critical role in male development.
Amino Acid Sequence↗
Selective suppression of the catalytic activity of cDNA-expressed cytochrome P4502B1 toward polycyclic hydrocarbons in the microsomal membrane: modification of this effect by specific amino acid substitutions.
Human hepatoma HEPG2 cells were infected with recombinant vaccinia virus vectors containing cDNAs encoding both known and variant rat cytochromes P450 (CYP). CYP2B1 and CYP2B2 cytochromes were equally well expressed (110-140 pmol/mg of microsomal protein) and catalyzed metabolism of 7,12-dimethylbenz[a]anthracene (DMBA). Their regioselectivity for DMBA metabolism paralleled that of the respective purified rat liver enzymes and reproduced previously reported regioselective differences between CYP2B1 and CYP2B2 [Wilson et al. (1984) Carcinogenesis 5, 1475-1483]. CYP2A1 and CYP2A2 expressed in HEPG2 microsomes exhibited nearly equal DMBA-metabolizing activities that closely matched that of purified CYP2A1. Although purified rat liver CYP2B1 was 3 times more active than purified rat liver CYP2B2, the expressed recombinant microsomal CYP2B1 (rCYP2B1) was 20 times less active than rCYP2B2, where activity matched that of the purified cytochrome. Microsomal suppression of rCYP2B1 catalytic activity was also observed for benzo[a]pyrene. Specific amino acid substitutions at equivalent positions of the completely homologous NH2-terminal halves of rCYP2B1 and rCYP2B2 changed this suppression effect. Thus, a L58----F, I114----F double mutant exhibited 3 times the normal activity for rCYP2B1 while remaining inhibitory for rCYP2B2. The single substitutions produced very different effects. The L58----F substitution prevented expression of rCYP2B1, while the I114----F substitution was inhibitory for both rCYP2B1 and rCYP2B2 (40 and 70%). A single E282----V mutation produced a stimulation of rCYP2B1 activity comparable to that of the L58----F, I114----F double substitution.(ABSTRACT TRUNCATED AT 250 WORDS)
9,10-Dimethyl-1,2-benzanthracene↗
Effects of the adenylate cyclase activator forskolin and its inactive derivative 1,9-dideoxyforskolin on insect cytochrome P-450 dependent steroid hydroxylase activity.
The adenylate cyclase activator forskolin and its pharmacologically inactive derivative 1,9-dideoxyforskolin were found to inhibit in a dose-dependent fashion the ecdysone 20-monooxygenase activity associated with wandering stage larvae of Drosophila melanogaster and fat body and midgut from last instar larvae of the tobacco hornworm, Manduca sexta. The concentrations of these labdane diterpenes required to elicit a 50% inhibition of the cytochrome P-450 dependent steroid hydroxylase activity in the insect tissues ranged from approximately 5 x 10(-6) to 5 x 10(-4) M.
Adenylyl Cyclases↗
Relative activity of structural analogues of amsacrine against human leukemia cell lines containing amsacrine-sensitive or -resistant forms of topoisomerase II: use of computer simulations in new drug development.
Anilino analogues of amsacrine showed increased activity against amsacrine (AMSA)-resistant cell lines when compared with the parent compound, but the mechanisms of amsacrine resistance in these lines were unknown (Finlay, G. J., Baguley, B. C., Snow, K., and Judd, W., J. Natl. Cancer Inst., 82: 662-667, 1990). We tested the cytotoxic and DNA-cleaving activities of two amsacrine analogues which were derivatives of 9-anilinoacridine (1'-methylcarbamate and 1'-benzenesulfonamide) against an amsacrine-resistant human leukemia cell line (HL-60/AMSA) whose resistance is due to an amsacrine-resistant topoisomerase II. Neither agent could overcome the amsacrine resistance of HL-60/AMSA. Neither agent could induce HL-60/AMSA topoisomerase II-mediated cleavage of DNA in an isolated biochemical system, although at high concentrations the two analogues could inhibit HL-60/AMSA topoisomerase II-mediated DNA strand passage. Both analogues were at least as active, if not more active, than amsacrine against amsacrine-sensitive HL-60 and its topoisomerase II. Comparison of the cellular and biochemical results with those from computer simulation of the energy-minimized structures of amsacrine, its inactive isomer o-AMSA, and the two new active analogues suggests the following possibilities: (a) the positioning of the potential topoisomerase II-binding site (1'-anilino group) of the two new drugs resembles the positioning of this site in amsacrine; (b) the HL-60 topoisomerase II has a binding site which interacts with amsacrine and the two anilino analogues but not with o-AMSA, an analogue with altered positioning of the methoxy group; (c) the HL-60/AMSA topoisomerase II interacts with reduced affinity with amsacrine and the two anilino analogues, although HL-60/AMSA topoisomerase II still interacts with the structurally distinct topoisomerase II-reactive nonintercalator, etoposide; (d) because of their higher DNA binding affinity or the greater possible positions of their side groups in comparison to amsacrine, the two analogues can, at high concentrations, inhibit the strand-passing activity of HL-60/AMSA topoisomerase II.
Amsacrine↗
A placebo controlled trial of remoxipride in the prevention of relapse in chronic schizophrenia.
Sixty-two DSM III chronic schizophrenic inpatients were selected for a double-blind, placebo controlled, multi-centre, relapse prevention study of remoxipride, a selective dopamine (D2)-receptor antagonist. After a 1 month placebo washout, 23 patients had relapsed and were withdrawn. Of the remaining patients 19 were randomised to remoxipride (150-300 mg daily) and 20 to placebo. Their median age was 58 years, 26 were male, and the median duration of illness was 33 years. After 24 weeks a further total of 8 remoxipride and 17 placebo patients had been withdrawn. Excluding three patients withdrawn for reasons other than relapse, the comparative relapse rates were 37% and 75%, respectively (P = 0.015). Efficacy analyses using clinical global impression (P = 0.04) and change in BPRS scores (P = 0.016) were in favour of remoxipride. Extrapyramidal symptoms were minimal in both groups. Treatment emergent adverse events were similar in the two groups. Remoxipride is therefore of potential value as a safe drug which is both effective and well tolerated in the long term management of chronic schizophrenic patients.
Adult↗