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Biomedical subjects

D H Hamer

Publications and source records attributed to D H Hamer.

At least 37 records · Page 2Linked to original sources
PubMed1995

Development and familiality of sexual orientation in females.

The development and familial clustering of sexual orientation were studied in 358 heterosexual, bisexual, and homosexual women. Sexual orientation, as measured by the Kinsey scales, was diverse yet showed statistical congruity and stability over a 1- to 1.5-year time span. Developmental patterns, as measured by retrospective reports on the ages of first sexual or romantic attraction and of self-acknowledgement of sexual orientation were very similar in the heterosexual and lesbian subjects except for the difference in object choice. The bisexual subjects displayed intermediate patterns that were more similar to the heterosexuals' on most facets yet closer to the lesbian subjects' on other dimensions. Familial clustering of nonheterosexual orientation was significant. Using two criteria, elevated rates of nonheterosexuality were found in four classes of relatives: sisters, daughters, nieces, and female cousins through a paternal uncle. The current data are not sufficient to distinguish between genetic and shared environmental sources of this familial aggregation. We discuss the possibility of using developmental criteria to differentiate between inherited and cultural sources of variation in female sexual orientation.

Adolescent↗
PubMed1995

Linkage between sexual orientation and chromosome Xq28 in males but not in females.

We have extended our analysis of the role of the long arm of the X chromosome (Xq28) in sexual orientation by DNA linkage analyses of two newly ascertained series of families that contained either two gay brothers or two lesbian sisters as well as heterosexual siblings. Linkage between the Xq28 markers and sexual orientation was detected for the gay male families but not for the lesbian families or for families that failed to meet defined inclusion criteria for the study of sex-linked sexual orientation. Our results corroborate the previously reported linkage between Xq28 and male homosexuality in selected kinships and suggest that this region contains a locus that influences individual variations in sexual orientation in men but not in women.

Base Sequence↗
PubMed1995

Recombination and allelic association in the Xq/Yq homology region.

The ends of the long arms of the human X and Y chromosomes contain a homologous region that can undergo sequence exchange. We have developed new polymorphic markers to analyze the genetic behavior of this region in the three-generation CEPH reference families. These Xq/Yq markers undergo crossovers in approximately 2% of male meioses in a pattern consistent with reciprocal recombination rather than gene conversion. Although the rate of recombination in males is significantly higher than in females or in autosomal sequences, it is more than an order of magnitude lower than in the short arm pseudoautosomal region at Xp/Yp. The Xq/Yq markers exhibit allelic association with one another, but not with markers in the X-specific or Y-specific regions of the sex chromosomes. Hence the Xq/Yq homology region displays behavior that is intermediate between sex-linked and true pseudoautosomal, and is unlikely to be essential for proper chromosome segregation.

Alleles↗
PubMed1994

Purification and characterization of a protein that binds to metal responsive elements of the human metallothionein IIA gene.

Metal responsive element (MRE) is a cis-acting DNA motif located in the upstream region of vertebrate metallothionein genes, which can confer metal responsiveness on downstream heterologous promoters. A protein that binds to the MRE sequence in a zinc-dependent manner (zinc regulatory factor; ZRF) was purified 16,000-fold from HeLa cell nuclear extracts by means of the avidin-biotin method, in which a complex formed between ZRF and a biotinylated probe containing MRE was trapped by streptavidin-agarose beads, and ZRF was recovered by salt extraction. By repeating the method three times, a homogeneous 116-kDa protein was obtained whose recovery was zinc-dependent and MRE sequence-specific. UV cross-linking analysis also revealed that a protein that specifically binds to MRE has the same molecular mass as the purified protein. Zinc-dependent and MRE sequence-specific footprints of ZRF were obtained on MREa and MREb in the upstream region of the human metallothionein IIA gene. The ZRF-MRE complex dissociates by the addition of chelating reagents, suggesting a direct role of zinc ions in the DNA binding of ZRF. Partial amino acid sequences of ZRF were found to be highly homologous to those of a mouse MRE-binding protein, mMTF-1.

Amino Acid Sequence↗
PubMed1994

Attachment of Cryptosporidium parvum sporozoites to MDCK cells in vitro.

The initial attachment of Cryptosporidium parvum sporozoites to host cells in vivo may be a critical event in the pathogenesis of this infection. The molecular basis of attachment and the conditions influencing this host-parasite interaction have not been studied systematically. Therefore, we have developed a sporozoite attachment model by using paraformaldehyde-fixed Madin-Darby canine kidney (MDCK) cells. Attachment of sporozoites to fixed MDCK cells was quantitated by indirect immunofluorescence and confirmed by transmission electron microscopy. Attachment in this system was time, temperature (37 degrees C), and pH (7.2 to 7.6) dependent. Dose-response studies demonstrated that the attachment of sporozoites to fixed MDCK cells was a saturable process. Attachment was enhanced in the presence of 10 mM manganese, 1 mM calcium, and 1 to 10 mM zinc. Attachment of sporozoites to MDCK cells was inhibited in a dose-dependent manner by polyclonal anti-Cryptosporidium antisera and by purified immunoglobulin G (IgG). This model will be useful for the study of parasite and host cell molecules involved in the initial interaction of C. parvum sporozoites with their target cell.

Adhesiveness↗
PubMed1993

A linkage between DNA markers on the X chromosome and male sexual orientation.

The role of genetics in male sexual orientation was investigated by pedigree and linkage analyses on 114 families of homosexual men. Increased rates of same-sex orientation were found in the maternal uncles and male cousins of these subjects, but not in their fathers or paternal relatives, suggesting the possibility of sex-linked transmission in a portion of the population. DNA linkage analysis of a selected group of 40 families in which there were two gay brothers and no indication of nonmaternal transmission revealed a correlation between homosexual orientation and the inheritance of polymorphic markers on the X chromosome in approximately 64 percent of the sib-pairs tested. The linkage to markers on Xq28, the subtelomeric region of the long arm of the sex chromosome, had a multipoint lod score of 4.0 (P = 10(-5), indicating a statistical confidence level of more than 99 percent that at least one subtype of male sexual orientation is genetically influenced.

Female↗
PubMed1990

Gonococcal pericarditis with tamponade in a patient with systemic lupus erythematosus.

Pericarditis is one of the most frequent manifestations of systemic lupus erythematosus; however, purulent pericarditis and tamponade are rare. We describe a patient with systemic lupus erythematosus and culture-proven gonococcal arthritis who developed purulent pericarditis with intracellular gram-negative diplococci. Evidence of tamponade was seen on echocardiography. There has not been a reported case of Neisseria gonorrhoeae in pericardial fluid or tissue since the introduction of antibiotics.

Adult↗
PubMed1989

Fine mapping of a mouse metallothionein gene metal response element.

Metal-regulated transcription of metallothionein (MT) genes in higher eucaryotes involves multiple copies of a highly conserved 17-base-pair metal-regulatory element (MRE). We have assayed by transient transfection the ability of mouse MT-I element d (MREd) to confer metal responsivity to constructs containing the mouse MT-I TATA box and the bacterial chloramphenicol acetyltransferase indicator gene. A single copy of MREd works bidirectionally to afford a three- to fourfold induction, and dual copies act cooperatively to yield a 10- to 20-fold response. Element d responds to the same spectrum of heavy metals as doses the complete MT gene promoter. The sequences involved in induction by metals were delineated by analyzing point mutations in MREd. While nucleotides of the highly conserved core sequence TGCPuCXC are critical, substitutions in the less conserved regions affect the induction response only marginally. These sequences include residues of a potential Sp1-binding site, suggesting that if Sp1 binds to MREd, it has little if any role in induction by metals.

Animals↗
PubMed1988

Overexpression of metallothionein confers resistance to anticancer drugs.

Resistance to antineoplastic agents is the major obstacle to curative therapy of cancer. Tumor cell lines with acquired resistance to the antineoplastic agent cis-diamminedichloroplatinum(II) overexpressed metallothionein and demonstrated cross-resistance to alkylating agents such as chlorambucil and melphalan. Human carcinoma cells that maintained high levels of metallothionein because of chronic exposure to heavy metals were resistant to cis-diamminedichloroplatinum(II), melphalan, and chlorambucil. Furthermore, cells transfected with bovine papilloma virus expression vectors containing DNA encoding human metallothionein-IIA were resistant to cis-diamminedichloroplatinum(II), melphalan, and chlorambucil but not to 5-fluorouracil or vincristine. Thus, overexpression of metallothionein represents one mechanism of resistance to a subset of clinically important anticancer drugs.

Animals↗