Karyotypes of seven species of bats from Thailand (Chiroptera,Mammalia)

Summary Karyotypes ofMyotis siligorensis, Myotis mystacinus, Pipistrellus pulveratus, Tylonycteris robustula, Miniopterus schreibersi fuliginosus, Hipposideros fulvus andAselliscus stoliczkanus from Thailand are investigated.Acknowledgment. The authors are very grateful to Dr N. Ratanawarabhan, Mrs S. Sittilert, P. Noonpakdee and S. Kuanchalern of Thailand Institute of Scientific and Technological Research for their valuable advice and assistance during our field survey in Thailand.     

Heat shock proteins and infection: interactions of pathogen and host.

Invasive microorganisms encounter defensive attempts of the host to starve, destroy and eliminate the infection. In experimental model systems aiming to imitate defensive actions of the host, microorganisms respond by the rapid acceleration in the rate of expression of heat shock and other stress proteins. Heat shock proteins (hsp) of most if not all pathogens are major immune targets for both B- and T-cells. Host cells involved in the defensive action cannot avoid exposure to their own reactive compounds, such as oxygen radicals, resulting in premature cell death and tissue damage. Long-term consequences to the host may include cancer. In cells in tissue culture, induction of host-specific hsps occurs upon exposure to oxidants and in viral infections. Drugs that bind to members of the hsp70 family induce peroxisome proliferation and hepatocarcinoma, but may open the way for the development of novel drugs in support of antimetabolite treatment of infections and cancer.     

Cyclosporine is angiostatic

The systemic effect of the immunosuppressive drug cyclosporine (CS) on formation of new blood vessels was studied quantitatively in rats using the mesenteric-window assay. Angiogenesis was induced by i.p. injection of saline. CS at a s.c. dose of 4 mg/kg/day, which is in the range used clinically, suppressed angiogenesis (inhibiting branching or tortuosity more than spatial expansion), and appeared to be non-toxic. This is the first report on an apparently selective angiostatic effect of CS. The finding is likely to have implications for the clinical use of CS, not only in certain types of organ transplantation but possibly also in psoriasis and other angiogenesis-dependent diseases.     

Mutation of the matrix metalloproteinase 2 gene (MMP2) causes a multicentric osteolysis and arthritis syndrome.

The inherited osteolyses or 'vanishing bone' syndromes are a group of rare disorders of unknown etiology characterized by destruction and resorption of affected bones. The multicentric osteolyses are notable for interphalangeal joint erosions that mimic severe juvenile rheumatoid arthritis (OMIMs 166300, 259600, 259610 and 277950). We recently described an autosomal recessive form of multicentric osteolysis with carpal and tarsal resorption, crippling arthritic changes, marked osteoporosis, palmar and plantar subcutaneous nodules and distinctive facies in a number of consanguineous Saudi Arabian families. We localized the disease gene to 16q12-21 by using members of these families for a genome-wide search for homozygous-by-descent microsatellite markers. Haplotype analysis narrowed the critical region to a 1.2-cM region that spans the gene encoding MMP-2 (gelatinase A, collagenase type IV; (ref. 3). We detected no MMP2 enzymatic activity in the serum or fibroblasts of affected family members. We identified two family-specific homoallelic MMP2 mutations: R101H and Y244X. The nonsense mutation effects a deletion of the substrate-binding and catalytic sites and the fibronectin type II-like and hemopexin/TIMP2 binding domains. Based on molecular modeling, the missense mutation disrupts hydrogen bond formation within the highly conserved prodomain adjacent to the catalytic zinc ion.     

Why the Afshar experiment does not refute complementarity

A modified version of Young's experiment by Shahriar Afshar demonstrates that, prior to what appears to be a “which-way” measurement, an interference pattern exists. Afshar has claimed that this result constitutes a violation of the Principle of Complementarity. This paper discusses the implications of this experiment and considers how Cramer's Transactional Interpretation easily accommodates the result. It is also shown that the Afshar experiment is analogous in key respects to a spin one-half particle prepared as “spin up along x”, subjected to a nondestructive confirmation of that preparation, and post-selected in a specific state of spin along z. The terminology “which-way” or “which-slit” is critiqued; it is argued that this usage by both Afshar and his critics is misleading and has contributed to confusion surrounding the interpretation of the experiment. Nevertheless, it is concluded that Bohr would have had no more problem accounting for the Afshar result than he would in accounting for the aforementioned pre- and post-selection spin experiment, in which the particle's preparation state is confirmed by a nondestructive measurement prior to post-selection. In addition, some new inferences about the interpretation of delayed choice experiments are drawn from the analysis.     

Induction of hemopoietic chimerism in the caprine fetus by intraperitoneal injection of fetal liver cells

Summary Intraperitoneal injection of allogeneic liver cells from 43-day-old male fetuses into normal 60-day female goat fetuses resulted in persistent hemopoietic chimerism in surviving recipients without clinical evidence of graft-versus-host disease. Transplantation of normal fetal liver cells into preimmunocompetent goat fetuses affected with -D-mannosidosis may provide an alternative strategy for evaluating hemopoietic stem cell transplantation in the treatment of human lysosomal storage diseases.     

Goniothalamicin and annonacin: Bioactive acetogenins fromGoniothalamus giganteus (Annonaceae)

Summary Using brine shrimp lethality for activity-directed fractionation, goniothalamicin (I), a new tetrahydroxy-mono-tetrahydrofuran fatty acid -lactone (acetogenin), has been isolated from ethanolic extracts of the stem bark ofGoniothalamus giganteus Hook. f., Thomas (Annonaceae). This novel compound was found to be cytotoxic and insecticidal and inhibited the formation of crown gall tumors on potato discs. Annonacin (II), the only other reported mono-tetrahydrofuran acetogenin, was also isolated; the previously reported 9ASK (astrocytoma reversal) activity ofII was confirmed, andII is now also found to be weakly active against 3PS murine leukemia.     

Pharmacodynamic profile of CQP 201-403, a novel 8α-amino-ergoline

Summary The profile of action in animals of CQP 201-403, a novel 8-amino-ergoline, is in most aspects that of a very potent dopaminomimetic, both as a prolactin secretion inhibitor, and at the levels of the CNS and the cardiovascular system. Qualitatively CQP 201-403 differs slightly from bromocriptine and apomorphine in its effects on the CNS (no influence on serotonin metabolism in the rat cortex; induction of masculine mounting behavior in rats) and the cardiovascular system of the dog (reflex tachycardia in response to a blood-pressure fall). In man the new compound proved to be highly active in lowering prolactin serum levels and to be more potent than bromocriptine (Parlodel^®).In memory of Dr Annemarie Closse, who died 14 June 1987.     

Changes in erythrocyte membrane lipid composition affect the transient decrease in membrane order which accompanies insulin receptor down-regulation

We have recently demonstrated, using electron paramagnetic resonance (EPR) spectroscopy, that insulin receptor internalization in response to insulin incubation (down-regulation) in human erythrocytes is accompanied by a transient decrease in membrane order, as measured by the 2T order parameter. Since membrane lipids play such an important role in receptor internalization, we investigated the possible effects that an alteration of the normally-occurring lipid profile might have on down-regulation and the concomitant transient decrease in membrane order. Consequently, human erythrocytes enriched with cholesterol and erythrocytes from cirrhotic patients were examined, because both of these groups of cells have a higher cholesterol/phospholipid molar ratio (CH/PL) than controls. The 5-nitroxystearate spin label, which inserts into the lipid bilayer of cell membranes, was used to monitor changes in 2T for a 3-h period at 37°C. We report here that both cholesterol-enriched and cirrhotic erythrocytes do not down-regulate, as demonstrated by binding assays, and that they do not show the typical transient decrease in membrane order observed in controls. The results seem to indicate that a more ordered membrane inhibits internalization of the insulin receptor in erythrocytes, and that an increase in membrane disorder is necessary for insulin receptor down-regulation.