Phorbol esters down-regulate alpha-fetoprotein gene expression without affecting growth in fetal hepatocytes in primary culture

The mammalian spermatozoon undergoes continuous modifications during spermatogenesis, maturation in the epididymis, and capacitation in the female reproductive tract. Only the capacitated spermatozoa are capable of binding the zona-intact egg and undergoing the acrosome reaction. The fertilization process is a net result of multiple molecular events which enable ejaculated spermatozoa to recognize and bind to the egg's extracellular coat, the zona pellucida (ZP). Sperm-egg interaction is a species-specific event which is initiated by the recognition and binding of complementary molecule(s) present on sperm plasma membrane (receptor) and the surface of the ZP (ligand). This is a carbohydrate-mediated event which initiates a signal transduction cascade resulting in the exocytosis of acrosomal contents. This step is believed to be a prerequisite which enables the acrosome reacted spermatozoa to penetrate the ZP and fertilize the egg. This review focuses on the formation and contents of the sperm acrosome as well as the mechanisms underlying the induction of the acrosome reaction. Special emphasis has been laid on the synthesis, processing, substrate specificity, and mechanism of action of the acid glycohydrolases present within the acrosome. The hydrolytic action of glycohydrolases and proteases released at the site of sperm-zona binding, along with the enhanced thrust generated by the hyperactivated beat pattern of the bound spermatozoon, are important factors regulating the penetration of ZP. We have discussed the most recent studies which have attempted to explain signal transduction pathways leading to the acrosomal exocytosis.     

Neutralization of IL-12 demonstrates the existence of discrete organ-specific phases in the control of Leishmania donovani

Aspergillus nidulans grows by apical extension of multinucleate cells called hyphae that are subdivided by the insertion of crosswalls called septa. Apical cells vary in length and number of nuclei, whereas subapical cells are typically 40 microm long with three to four nuclei. Apical cells have active mitotic cycles, whereas subapical cells are arrested for growth and mitosis until branch formation reinitiates tip growth and nuclear divisions. This multicellular growth pattern requires coordination between localized growth, nuclear division, and septation. We searched a temperature-sensitive mutant collection for strains with conditional defects in growth patterning and identified six mutants (designated hyp for hypercellular). The identified hyp mutations are nonlethal, recessive defects in five unlinked genes (hypA-hypE). Phenotypic analyses showed that these hyp mutants have aberrant patterns of septation and show defects in polarity establishment and tip growth, but they have normal nuclear division cycles and can complete the asexual growth cycle at restrictive temperature. Temperature shift analysis revealed that hypD and hypE play general roles in hyphal morphogenesis, since inactivation of these genes resulted in a general widening of apical and subapical cells. Interestingly, loss of hypA or hypB function lead to a cessation of apical cell growth but activated isotropic growth and mitosis in subapical cells. The inferred functions of hypA and hypB suggest a mechanism for coordinating apical growth, subapical cell arrest, and mitosis in A. nidulans.     

Stimulation of insulin release and potentiation of the insulinotropic action of antidiabetic agents by 1,2,3-tri(methylsuccinyl)glycerol ester in anaesthetized rats

The study was designed to investigate the effect of creatine monohydrate ingestion (20 g daily for 5 days) on performance in 45 s maximal continuous jumping and in all-out treadmill running at 20 km x h(-1), (inclination 5 degrees, duration approximately 60s). The participants were qualified sprinters and jumpers. The effect of creatine was compared with placebo in a double-blind design. Creatine (Cr) supplementation led to a significant enhancement of performance capacity in the jumping test by 7% during the first 15 s and by 12% during the second 15 s of the exercise. The positive effect of Cr supplementation was not observed in the last third of the continuous jumping exercise, when the contribution of anaerobic metabolism was decreasing. The time of intensive running up to exhaustion improved by 13%. The results show that Cr supplementation helps to prolong the time during which the maximal rate of power output could be maintained.     

Oral dosing of rats with OM-89 results in the appearance of specific OM-89 antibodies of the IgG2a isotype: possible significance in the treatment of rheumatoid arthritis

OM-89 is a glycoprotein-rich extract of Escherichia coli shown to be effective in the treatment of rheumatoid arthritis (RA). It has been reported that oral dosing of animals results in the appearance of specific OM-89 antibodies. In the current study we have investigated some of the immunoglobulin isotypes that may be involved. OM-89 antibodies of IgG1, IgG2a and IgM isotypes were measured by ELISA in serum from rats dosed three times a week for 3 weeks at 4 or 40 mg kg(-1). The results showed a small but significant rise in IgM and a greater rise in IgG2a. The possibility that antigens within OM-89 (e.g. hsp65) may have homology with antigens involved in RA raises the possibility that OM-89 antibodies, particularly of the IgG2 class, may block pathogenic antigens from being recognized by T cells.     

Long-term results of total hip replacement in young patients who had ankylosing spondylitis. Eighteen to thirty-year results with survivorship analysis

We determined the long-term results of total hip replacement in a series of young patients who had ankylosing spondylitis. Between 1966 and 1978, forty-three Charnley low-friction arthroplasties were performed in twenty-four patients who had an average age of 28.8 years (range, nineteen to thirty-nine years) at the time of the operation. There were seventeen men and seven women. The average duration of follow-up for the series was 22.7 years (range, one month [a perioperative death] to 30.3 years). Four patients (seven hips) had died an average of 12.6 years (range, one month to 18.7 years) after the operation. The twenty surviving patients had clinical and radiographic follow-up until the time of writing or until both of the original components had been revised. All patients had substantial relief of pain and improvement of function and the range of motion of the joint. Twenty-one patients (88 per cent; thirty-nine hips) were completely free of pain (6 points, according to the scale of Merle d'Aubigne and Postel), and the remainder had only slight discomfort (5 points). Ten acetabular components and one femoral component were revised because of aseptic loosening, and one patient had a revision of both components because of late deep infection. Three additional femoral components were revised during a revision operation for a loose acetabular component. Although the femoral components were not loose, they had been in place for more than ten years and it was thought likely that the bearing surface was damaged. The average time to revision was 13.3 years (range, 4.0 to 20.3 years). At an average of 22.7 years, thirty-eight (88 per cent) of the original femoral components and thirty-two (74 per cent) of the original acetabular components remained in situ. The average annual rate of acetabular wear was 0.12 millimeter for the entire series. Only six hips (14 per cent) had minor heterotopic ossification, and none of the hips had clinically important ossification (class III or IV according to the system of Brooker et al.). To our knowledge, the present report describes the largest series of total hip arthroplasties, with the longest duration of follow-up, in young patients who had ankylosing spondylitis. Survivorship analysis with use of the Kaplan-Meier method revealed that the probability of survival of the femoral component (with 95 per cent confidence intervals) was 91 per cent (83 to 99 per cent) at twenty years and 83 per cent (72 to 94 per cent) at thirty years. The probability of survival of the acetabular components was 73 per cent (61 to 84 per cent) at twenty years and 70 per cent (57 to 83 per cent) at thirty years. The probability that both components would survive was 91 per cent (82 to 100 per cent) at ten years, 73 per cent (61 to 84 per cent) at twenty years, and 70 per cent (57 to 83 per cent) at thirty years. The Charnley low-friction arthroplasty provided consistently good long-term results, with a low rate of complications and revisions, in this group of young patients.     

An ecology of text: using text retrieval to study alife on the net

I introduce a new alife model, an ecology based on a corpus of text, and apply it to the analysis of posts to USENET News. In this corporal ecology posts are organisms, the newsgroups of NetNews define an environment, and human posters situated in their wider context make up a scarce resource. I apply latent semantic indexing (LSI), a text retrieval method based on principal component analysis, to distill from the corpus those replicating units of text. LSI arrives at suitable replicators because it discovers word co-occurrences that segregate and recombine with appreciable frequency. I argue that natural selection is necessarily in operation because sufficient conditions for its occurrence are met: replication, mutagenicity, and trait/fitness covariance. I describe a set of experiments performed on a static corpus of over 10,000 posts. In these experiments I study average population fitness, a fundamental element of population ecology. My study of fitness arrives at the unhappy discovery that a flame-war, centered around an overly prolific poster, is the king of the jungle.