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.     

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.     

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.     

Lack of effect of dihydroergotamine on endothelial and smooth muscle cell proliferation and endothelial cell prostanoid production

Summary The most important effect of dihydroergotamine is venoconstriction, but certain metabolic effects and changes in vessel prostanoid activity have also been suggested. In this study endothelial cell production of 6-keto PGF₁ and TxB₂ was quantitated in vitro. No evidence of altered prostanoid production was noted after incubation with dihydroergotamine (exposure ranging from 5×10^–3 to 5×10^–7 g/l). Similarly, no effect of dihydroergotamine on the growth rates of endothelial cells or smooth muscle cells in vitro was documented.     

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.     

Definition of a consensus binding site for p53.

Recent experiments have suggested that p53 action may be mediated through its interaction with DNA. We have now identified 18 human genomic clones that bind to p53 in vitro. Precise mapping of the binding sequences within these clones revealed a consensus binding site with a striking internal symmetry, consisting of two copies of the 10 base pair motif 5'-PuPuPuC(A/T)(T/A)GPyPyPy-3' separated by 0-13 base pairs. One copy of the motif was insufficient for binding, and subtle alterations of the motif, even when present in multiple copies, resulted in loss of affinity for p53. Mutants of p53, representing each of the four "hot spots" frequently altered in human cancers, failed to bind to the consensus dimer. These results define the DNA sequence elements with which p53 interacts in vitro and which may be important for p53 action in vivo.     

Heterogeneous responses of canine basilar and middle cerebral arteries to serotonin at normal and high CO2 tension

The responses of basilar arteries (BAs) to serotonin were attenuated by high \(P_{CO_2 } \) (86±1 mm Hg) and the pH matched acidotic solution ( \(P_{CO_2 } \) 37±1 mm Hg), whereas the responses of middle cerebral arteries (MCAs) were not. High \(P_{CO_2 } \) decreased the basal tone of both arteries, and the changes in basal tone due to high \(P_{CO_2 } \) were not influenced by 3×10^?7 M imipramine, 10^?5 M pargyline or 10^?4 M aspirin. The responses of BAs to serotonin were attenuated by high \(P_{CO_2 } \) in the presence of imipramine, pargyline and aspirin. The responses of MCAs to serotonin were not influenced by high \(P_{CO_2 } \) in the presence of pargyline and aspirin, but attenuated by high \(P_{CO_2 } \) in the presence of imipramine.     

C1 inhibitor hinge region mutations produce dysfunction by different mechanisms.

Heterozygosity for a mutant dysfunctional C1 inhibitor protein, a member of the serine proteinase inhibitor (serpin) superfamily, results in type II hereditary angioneurotic oedema. We identified a "hinge" region mutation in C1 inhibitor with a Val to Glu replacement at P14 Val-432. Recombinant C1 inhibitors P10 Ala-->Thr and P14Val-->Glu did not form stable complexes with fluid phase C1s or kallikrein. The P14 Val-->Glu mutant, however, was cleaved to a 96K form by C1s, while the P10 Ala-->Thr mutant was not. The recombinant P10 mutant also did not complex with C1s, kallikrein or beta-factor Xlla-Sepharose. The two mutations, therefore, result in dysfunction by different mechanisms: in one (P14 Val-->Glu), the inhibitor is converted to a substrate, while in the other (P10 Ala-->Thr), interaction with target protease is blocked.