Biomedical subjects

L E Kerr

Publications and source records attributed to L E Kerr.

At least 19 recordsLinked to original sources

PubMed2000

Caspase 6 activity initiates caspase 3 activation in cerebellar granule cell apoptosis.

Using a well documented ex vivo system consisting of rodent cerebellar granule cells (CGCs) the activation of caspases 3 and 6 during apoptosis induced by withdrawal of trophic support was analyzed. At the time of deprivation, the addition of the irreversible, broad-spectrum caspase inhibitor zVADfmk or the cell permeable, caspase 6 inhibitor CP-VEID-cho can transiently suppress the appearance of apoptosis, including the early appearance of DNA fragmentation. Using immunoblotting and fluorogenic peptide assays we observe deprivation-induced activation of caspases 3 and 6, but not caspase 9. Furthermore, active caspase 6 is capable of processing and activating procaspase 3 in cellular extracts prepared from non-apoptotic CGCs, whereas caspase 3 failed to activate caspase 6. In consonant with this, the cell permeable caspase 6 inhibitor prevented deprivation-induced caspase 3 activation whereas a cell permeable caspase 3 inhibitor, CP-DEVD-cho, had no effect on caspase 6 activation. This would indicate that caspase 6 is a significant inducer of the early caspase 3 activity in apoptotic CGCs.

Amino Acid Chloromethyl Ketones↗

PubMed1999

Cloning, sequencing and site of origin of the rat sperm receptor protein, ZP3.

The ZP3 gene encodes for a zona glycoprotein that serves as both a cell-specific binding site for capacitated spermatozoa and an inducer of acrosomal exocytosis during fertilisation. In this study we have determined the nucleotide sequence of rat ZP3 (accession no. Y10823), predicted primary amino acid structure and determined the cellular origin of this molecule within the ovary. Rat ZP3 was found to have an open reading frame of 1272 nucleotides encoding a polypeptide chain of 424 amino acids that was expressed exclusively by the actively growing oocyte population. Rat ZP3 exhibited 91%, 78% and 66% identity with the mouse, hamster and human homologues, respectively. Key features of mouse ZP3, including the number and location of cysteine and proline residues and N-linked glycosylation sites, were also conserved in the rat homologue. The putative O-linked glycosylation sites, a series of serine residues at ZP3(329-334), were also conserved in rat and mouse ZP3, although immediately downstream of this site the amino acid sequences deviated over a short stretch of amino acids. The hydropathicity profile revealed two hydrophobic domains. The first was associated with a putative N-terminal signal sequence which is unusual in the rat in possessing a proline residue at the -1 position relative to the signal cleavage site, a feature it shares with human and marmoset ZP3 but not mouse. The second hydrophobic domain was observed at the C-terminus downstream of a TGF-beta type III receptor domain that appears to be common to all ZP3 sequences examined to date.

Amino Acid Sequence↗

PubMed1998

Molecular basis of sperm-egg interaction and the prospects for immunocontraception.

As the molecular basis of sperm-egg interaction is resolved, so new opportunities are created for the development of immunological approaches to disrupt the process of conception. Thus, realisation that the zona glycoprotein, ZP3, serves as a specific receptor for spermatozoa, has prompted a detailed examination of its contraceptive potential. In primate models, recombinant ZP3 has been shown to suppress fertility very efficiently, however this efficacy is tempered by the appearance of adverse side-effects involving accelerated primordial follicle depletion and a lymphocytic infiltration of the ovarian stroma. Synthetic peptides encoding B-cell epitopes have been found to circumvent the lymphocyte response although the effectiveness of such reagents in preventing the loss of primordial follicles has not yet been determined. The induction of active immunity against sperm-specific antigens has also been shown to generate long term infertility in both males and females. Molecular and immunological techniques are now being used to produce a rapidly expanding list of unique sperm antigens which are currently being evaluated to determine their potential contribution to the development of safe, effective, contraceptive vaccines.

Animals↗

PubMed1996

Expression of protamine P2 in the testis of the common marmoset and man visualized using non-radioactive in-situ hybridization.

Information on the organization of the spermatogenic cycle of the common marmoset (Callíthrix jacchus), a small New World primate, is limited to a single histological report on the differentiation of spermatids. In the present study we have used non-radioactive in-situ hybridization with a cRNA probe directed against marmoset protamine 2, on fixed sections of marmoset and human testis to elucidate the organization of mature germ cells within the seminiferous epithelium. Specificity of the probe was checked on Northern blots; mP2 hybridized exclusively to mRNA in samples extracted from marmoset and human testis. In sections from human and marmoset testis, positive staining for mRNA was confined to round and elongating spermatids and in the human was reduced in samples from patients with incomplete spermatogenesis. In the human, P2 mRNA was present in groups of cells consistent with the presence of more than one stage of the spermatogenic cycle in transverse sections of individual tubules. In the marmoset, P2-positive cells were detected as a continuous ring of staining in the majority of sections of tubules whilst in others only a group(s) of cells was positive. We conclude that the arrangement of the spermatogenic wave in this New World primate may be intermediate between that seen in rodents (segmental) and in the human (helical).

Amino Acid Sequence↗

PubMed1995

Sperm antigens and immunocontraception.

The development of novel forms of contraception is one way in which the world population crisis is being tackled. The concept of a contraceptive vaccine based on gamete-specific antigens is a particularly attractive approach. Much research has been carried out to identify sperm antigens which could be used as the immunogen. The most encouraging leads have come from groups using monoclonal antibodies to identify and characterize sperm antigens important for fertility (e.g. SP-10, PH-20 and PH-30). Identification of these molecules will also enable the development of specific tests for the diagnosis of immune infertility.

Antibodies, Monoclonal↗

PubMed1990

Occupational health: a classic example of class conflict.

The history of class conflict in occupational health in the United States is illustrated by the current Pittston Company attack on coal miners' health benefits, the silicosis and asbestosis controversies, the corporate restrictions on state workers' compensation laws, and the unremitting management opposition to the federal Coal Mine Health and Safety Act of 1969 and the Occupational Health and Safety Act of 1970. A positive action program is presented as the basis for convening the long-overdue White House Conference on Occupational Health and Safety. Mining engineers are urged to support that action program to prevent unnecessary work-related death and disability.

Humans↗

PubMed1986