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Biomedical subjects

G L Mutter

Publications and source records attributed to G L Mutter.

51 records · Page 3Linked to original sources
PubMed1993

Differential expression of the proto-oncogenes c-abl and c-mos in developing mouse germ cells.

C-abl and c-mos, two proto-oncogenes with unique patterns of expression in gonadal tissues, were examined by in situ hybridization with respect to their expression in the germ line. C-abl transcripts were observed to be most abundant in late round spermatids and elongating spermatids. C-mos transcripts were also expressed in round spermatids, but at much reduced levels compared to the levels of c-abl. C-abl mRNAs were also detected in mouse oocytes which have entered the growth phase. This temporal specificity of accumulation of c-abl transcripts was similar to that observed for c-mos, which also accumulates in growing and fully grown oocytes (follicle stages 4-6). Quantitative evaluation suggested that c-abl mRNA levels in oocytes are at least an order of magnitude lower than those of c-mos transcripts.

Aging↗
PubMed1993

Sex chromosome composition of complete hydatidiform moles: relationship to metastasis.

OBJECTIVE: Complete hydatidiform moles have a substantial risk for subsequent development of persistent or metastatic gestational trophoblastic tumor. We evaluated the hypothesis that presence of a Y chromosome in a complete hydatidiform mole confers an increased risk for developing metastatic gestational trophoblastic tumor. STUDY DESIGN: The polymerase chain reaction was applied to archival paraffin-embedded molar-tissue to identify Y chromosome-positive dispermic moles in patients who did or did not develop metastatic disease. To reduce the chances of analytic error, consensus polymerase chain reaction primers directed at homologous but different genes present on both X and Y chromosomes were used. RESULTS: Y-chromosome sequences were identified in 7.7% (1/13) of the metastatic group and 9.1% (2/22) of the nonmetastatic group, a statistically insignificant difference. CONCLUSION: We are unable to confirm any increased risk for metastasis in Y chromosome-positive compared with Y chromosome-negative complete hydatidiform mole.

Base Sequence↗
PubMed1993

The sex ratio of normal and manipulated human sperm quantitated by the polymerase chain reaction.

OBJECTIVE: To establish the primary sex ratio, the relative abundance of X and Y chromosome-bearing sperm, in unselected sperm and in sperm selected by swim-up or Sephadex filtration (SpermPrep column; Fertility Technologies, Inc., Natick, MA). This was done to evaluate the possibility that these semen manipulations change the primary sex ratio. DESIGN: Ninety-eight unmanipulated semen samples were analyzed for sex chromosome content using quantitative polymerase chain reaction (PCR). A smaller number of samples was analyzed before and after either swim-up or Sephadex filtration. RESULTS: The mean percentage of all sex chromosomes identified as a Y chromosome in unmanipulated semen samples ranged from 41.9% to 56.7%, with a mean average of 50.3%. There was no significant change in sex chromosome composition after either swim-up (n = 17) or column filtration (n = 20). CONCLUSIONS: The chromosome compositions of semen samples from a large number of men have equal numbers of X and Y. Swim-up and SpermPrep filtration do not appear to alter the primary sex ratio.

Humans↗
PubMed1993

Oppositely imprinted genes H19 and insulin-like growth factor 2 are coexpressed in human androgenetic trophoblast.

Human uniparental gestations such as gynogenetic ovarian teratomas and androgenetic complete hydatidiform moles provide a model to evaluate the integrity of parent-specific gene expression--i.e., imprinting--in the absence of a complementary parental genetic contribution. We studied expression, in these tissues, of the oppositely imprinted genes H19, which is an embryonic nontranslated RNA, and insulin-like growth factor type 2 (IGF2). Normal gestations only express H19 from the maternal allele and express IGF2 from the paternal allele, whereas neither is expressed from the maternal genome of gynogenetic gestations, and both are expressed from the paternal genome of androgenetic gestations. Coexpression of H19 and IGF2 in the androgenetic tissues was in a single population of cells, mononuclear trophoblast--the same cell type expressing these genes in biparental placentas. These results demonstrate that a biparental genome may be required for expression of the reciprocal IGF2/H19 imprint. Alternatively, biparental expression may be a normal feature of some imprinted genes in specific cell types. Additional experiments with other imprinted genes will clarify whether this reflects global failure of the imprinting process or a change specific to the IGF2/H19 locus.

Base Sequence↗
PubMed1992

The effect of consecutive day inseminations on semen characteristics in an intrauterine insemination program.

This study demonstrates a statistically significant decrease in semen volume, sperm concentration, and sperm motility in samples obtained on the 2nd day of consecutive day inseminations in an IUI program. This diminution in semen characteristics persists despite sperm washing. The effects of a second ejaculation on semen parameters in oligospermic and asthenospermic men were mixed. Thus, in general, sperm-washing procedures cannot overcome the natural reduction in semen quality produced by frequent ejaculations. Clinicians may wish to use this information in timing IUI cycle inseminations.

Ejaculation↗
PubMed1991

Molecular diagnosis of sex chromosome aneuploidy using quantitative PCR.

Numeric sex chromosome imbalances, or aneuploidies, are present in several pathological conditions including tumors, abnormal gestations, and clinical syndromes. Here we report a method to identify karyotypic imbalances of the X and Y chromosomes using the polymerase chain reaction (PCR). The polymerase chain reaction was used to quantitatively coamplify the sex chromosome linked genes ZFX and ZFY. Quantitation was facilitated by 1) use of a single primer set which recognizes both templates, 2) incorporation of radiolabelled nucleotides during amplification, and 3) use of amplification conditions which minimize heteroduplex formation. High accuracy of the method was confirmed by concordance with values expected from titrated male and female DNAs and cells from patients with sex chromosome aneuploidy. This approach provides a rapid and reproducible method of evaluating relative abundance of allelic genes, and might be applied to detection of autosomal aneuploidy.

Aneuploidy↗
PubMed1991

Testis-specific expression of the human MYCL2 gene.

We have characterized the expression of MYCL2, an intronless X-linked gene related to MYCL1. RNase protection analysis of a panel of human normal and tumor tissues has revealed that MYCL2 is expressed almost exclusively in human adult normal testis; much lower levels of transcript were detected in one human lung adenocarcinoma. No MYCL2 transcript was found in human testis RNA obtained from second trimester fetuses. This observation suggests a germ cell rather than somatic cell origin of the transcript and possible developmental regulation of MYCL2. Northern blot analysis of poly(A)+ RNA from adult human normal testis with an antisense riboprobe revealed a transcript of approximately 4.8-kb, which is in agreement with the size predicted from the MYCL2 nucleotide sequence. Antisense transcripts were found spanning regions of MYCL2 corresponding to all three exons of MYCL1. No sizable open reading frame was seen for the MYCL2 antisense transcripts suggesting that they may represent either regulatory sequences or an intron of a gene encoded by the complementary strand. RNase protection assays and the 5' RACE protocol (Rapid Amplification of cDNA Ends) were used to address the localization of the transcription start site of the MYCL2 sense transcript and different putative promoters and transcription regulatory elements have been identified.

Amino Acid Sequence↗
PubMed1988

Evidence for the involvement of the proto-oncogene c-mos in mammalian meiotic maturation and possibly very early embryogenesis.

The c-mos proto-oncogene exists as a maternal mRNA in mammalian oocytes, in that it has been shown to accumulate in mouse oocytes during the growth phase and to be present at high levels in fully grown oocytes. The function of c-mos during the subsequent development of the oocytes and embryos was examined by determining the fate of the oocyte c-mos mRNAs by in situ hybridization and Northern blot hybridization analysis. A substantial decrease in the levels of c-mos transcripts was observed in oocytes undergoing meiotic maturation. By the two-cell stage, levels of c-mos transcripts dropped to below the limits of detection using in situ hybridization. c-mos transcripts remained undectable through the blastocyst stage of embryogenesis. Analysis of meiotic maturation in vitro permitted finer temporal resolution of the initial drop in c-mos levels. Between approximately 7 and 17 h of culture, the amount of c-mos mRNA fell to 18-43% of the levels found in the fully grown oocyte. This interval corresponds to the progression of meiotic maturation from metaphase I to metaphase II. Our in vivo studies showed that ovulation per se is not the stimulus for the drop in c-mos transcript levels, since preovulatory metaphase II oocytes exhibited this decline to a degree comparable to that of ovulated metaphase II oocytes. The development specificity of c-mos transcript levels suggests a role of this putative serine kinase in the meiotic maturation of mammalian germ cells.

Bucladesine↗
PubMed1987

Bleomycin-associated pulmonary fibrosis: rapidly fatal progression without chest radiotherapy.

Two patients with carcinoma of the tonsil were treated with bleomycin (396 and 224 units, respectively) but not with radiotherapy. Respiratory insufficiency led to death 45 and 52 days, respectively, after onset of therapy. Chest radiographs before bleomycin therapy revealed no evidence for lung disease. Postmortem examinations showed severe interstitial and intraalveolar pulmonary fibrosis. Comparably rapid progression from radiographically normal pulmonary parenchyma to fatal fibrosis has been documented previously only in patients with thoracic neoplasia as well as, in all but one instance, either prior or concurrent chest radiotherapy. These two cases indicate that chest radiotherapy is not a necessary cofactor for the development of rapidly progressive, fatal, diffuse interstitial pulmonary fibrosis after bleomycin therapy.

Aged↗
PubMed1987

Distinct developmental patterns of c-mos protooncogene expression in female and male mouse germ cells.

The protooncogene c-mos is expressed in murine reproductive tissues, producing transcripts of 1.7 and 1.4 kilobases in testis and ovary, respectively. In situ hybridization analysis of c-mos expression in histological sections of mouse ovaries revealed that oocytes are the predominant if not exclusive source of c-mos transcripts. c-mos transcripts accumulate in growing oocytes, increasing 40- to 90-fold during oocyte and follicular development. c-mos transcripts were also detected in male germ cells and are most abundant after the cells have entered the haploid stage of spermatogenesis. This developmentally regulated pattern of c-mos expression in oocytes and spermatogenic cells suggests that the c-mos gene product may have a function in normal germ-cell differentiation or early embryogenesis.

Animals↗
PubMed1987

Differential expression in murine somatic and germinal tissues of transcripts homologous to an abundant embryonal-carcinoma-cell mRNA.

EC1, a clone from a cDNA library of embryonal-carcinoma (EC) cells, was used to study the expression of the gene(s) homologous to this sequence in murine germ cells and somatic tissues. Northern-blot analysis was used to determine the size and relative abundance of ECl transcripts in EC cells, ovary, testis, liver, spleen, brain, thymus, and bone marrow. The stage-specific expression of EC1-related transcripts in meiotic cells was examined in enriched populations of testicular cells (meiotic prophase spermatocytes, early and late spermatids, and residual bodies). All tissues and cells examined contained mRNAs of approximately 1.3 and approximately 3.6 kb which were homologous to EC1. In RNA from liver and thymus, a faint, lower-molecular-weight transcript of 0.75 kb was seen. A unique pattern of expression was observed in male germ cells. In cells that had completed meiosis, two additional transcripts of 1.0 and 4.4 kb were visualized, as well as high levels of expression of the 1.3- and 3.6-kb species. Only the 1.3- and 3.6-kb transcripts were detected in ovarian RNAs. The high level and stage specificity of expression of EC1-related mRNAs in germ cells suggest that this gene may be important in meiosis or in germ-cell maturation.

Animals↗
PubMed1986

Isolation of a mouse cDNA coding for a developmentally regulated, testis-specific transcript containing homeo box homology.

A clone, pHBT-1, containing sequences homologous to Drosophila homeo boxes has been isolated from a mouse testis cDNA library. The sequence is 80% homologous at the DNA level and 88% homologous at the amino acid level to the homeo box sequence of the Antennapedia gene of Drosophila. Sequences flanking the 3' end of the homeo box are highly diverged from other murine homeo box-containing genes characterized to date. RNA blot hybridization analysis of mouse testis poly(A)+ RNA revealed transcripts of approximately 1.4 kb in length. Within the limits of sensitivity of detection of Northern blot analysis, no transcripts were seen in any of the adult somatic tissues examined. Other tissues that contain stem cells, namely those of the hemopoietic system, also lacked detectable amounts of HBT-1 transcripts. HBT-1 transcripts were limited to male germ cell-containing tissues, since RNAs from juvenile and adult ovaries did not contain detectable amounts of the 1.4-kb transcripts. Expression of the HBT-1 gene was not detected in embryonic testes, nor in tests of neonatal animals which contain germ cells up to the Type B stage of spermatogonial development. A role for the expression of the HBT-1 gene in the meiotic stages of male germ cell differentiation is postulated.

Animals↗
PubMedDate not supplied

Clonal analysis of sacrococcygeal "teratomas".

Congenital masses of the sacrococcygeal region commonly contain multiple tissues and have variously been subclassified as neoplasms or congenital hamartomas based on clinicopathological and embryological observations. We have used a polymerase chain reaction-based assay for nonrandom X chromosome inactivation to infer the clonality of three cogenital sacrococcygeal tumors previously diagnosed as teratomas. One solid immature teratoma was monoclonal, and a predominantly cystic histologically mature mass was polyclonal. A third immature teratoma was noninformative because of baseline asymmetry of polyclonal tissue X inactivation. We confirm that immature teratomas at this site appear to be monoclonal neoplasms and suggest that at least some histologically mature "teratomas" are more appropriately classified as hamartomas.

Cloning, Molecular↗