Interference Effect between ϕ and Λ(1520) Production Channels in the γp→K

The ϕ-Λ(1520) interference effect in the γp→K^{+}K^{-}p reaction has been measured for the first time in the energy range from 1.673 to 2.173 GeV. The relative phases between ϕ and Λ(1520) production amplitudes were obtained in the kinematic region where the two resonances overlap. The measurement results support strong constructive interference when K^{+}K^{-} pairs are observed at forward angles but destructive interference for proton emission at forward angles. Furthermore, the observed interference effect does not account for the sqrt[s]=2.1 GeV bump structure in forward differential cross sections for ϕ photoproduction. This fact suggests possible exotic structures such as a hidden-strangeness pentaquark state, a new Pomeron exchange, or rescattering processes via other hyperon states.

Near-threshold Lambda(1520) production by the gamma(p)-->K{+}Lambda(1520) reaction at forward K+ angles.

Differential cross sections and photon-beam asymmetries for the gamma(p)-->K{+}Lambda(1520) reaction have been measured with linearly polarized photon beams at energies from the threshold to 2.4 GeV at 0.6or=5/2 or by a new reaction process, for example, an interference effect with the phi photoproduction having a similar bump structure in the cross sections.

Incidence and significance of early aneurysmal rebleeding before neurosurgical or neurological management.

BACKGROUND AND PURPOSE: Rebleeding is a major cause of death and disability in aneurysmal subarachnoid hemorrhage (SAH); however, there has been no report focusing on rebleeding before hospitalization in neurosurgical or neurological institutions. The aim of this study was to clarify the incidence of prehospitalization rebleeding, its impact on the clinical course and prognosis in patients with aneurysmal SAH, and the possible factors inducing it. METHODS: In 273 patients who were admitted to our institution within 24 hours after the initial SAH bleeding and whose clinical course before admission could be fully evaluated, the patients' clinical conditions and CT findings on admission, operability, prognosis, and possible factors inducing rebleeding were comparatively evaluated between the patients with and without an episode of prehospitalization rebleeding. RESULTS: Of the 273 patients, 37 (13.6%) patients suffered from 39 episodes of rebleeding in the ambulance or at the referring hospital before admission to our hospital. The peak time of rebleeding was within 2 hours (77%), in which the incidence was statistically significant compared with that occurring 2 to 8 hours after the initial SAH bleeding (P<0.01). The group experiencing rebleeding showed more severe Hunt and Hess grades on admission, higher rates of intracerebral hematoma, of intraventricular hematoma, and of subdural hematoma on CT scan on admission, less operability, and poorer prognoses with statistically significant differences compared with the group that did not experience rebleeding. Systolic arterial pressure >160 mm Hg was a possible risk factor of rebleeding (odds ratio 3.1, 95% CI 1.5 to 6.8). CONCLUSIONS: Rebleeding during transfer and at the referring hospital is not rare. To improve overall outcome of aneurysmal SAH, the results obtained in this study should be made available to general practitioners and the doctors devoted to emergency medicine.

Interleukin-2 modulates the responsiveness to angiotensin II in cultured vascular smooth muscle cells.

Preincubation with interleukin-2 (IL-2), a T cell-derived cytokine, enhanced the increase in intracellular Ca2+ ([Ca2+]i) induced by angiotensin II (AII) in vascular smooth muscle cells (VSMC). IL-2 itself did not affect the basal [Ca2+]i level or the maximal response of [Ca2+]i increase induced by AII. Furthermore, IL-2-induced enhancement was not observed in the absence of extracellular Ca2+, suggesting that IL-2 enhances Ca2+ influx induced by AII. IL-2 also enhanced the stimulation of DNA synthesis induced by AII, although IL-2 alone did not stimulate DNA synthesis. Genistein, an inhibitor of protein tyrosine kinases, significantly inhibited IL-2-induced enhancement of both Ca2+ influx and DNA synthesis induced by AII. A neutralizing antibody against heparin-binding epidermal growth factor-like growth factor (HB-EGF) partially inhibited IL-2-induced enhancement of DNA synthesis induced by AII. These findings suggest that autocrine HB-EGF is partially involved in the mechanism of IL-2-induced enhancement of DNA synthesis. On the other hand IL-2 stimulated both glycosaminoglycan (GAG) and prostacyclin syntheses and enhanced the stimulation of both GAG and prostacyclin syntheses induced by AII. Therefore, IL-2 may play important roles in the pathogenesis of atherosclerosis and vascular disease by modulating the responsiveness to AII in VSMC.

Vascular casts of experimental subretinal neovascularization in monkeys.

The origin, course, and pattern of experimental subretinal neovascularization (SRN) in monkeys were studied with scanning electron microscopy (SEM) of Mercox preparations of the choroidal vascular bed. This technique allowed visualization of the entire circulation of the SRN lesion from both the retinal and scleral aspects. The SEM data is comparable to that of fluorescein angiography, but provides details not detectable by angiography. The afferent arteriole was traced back to the posterior ciliary artery of origin. In the early stages, the efferent vessels appeared to connect with the choriocapillaris; whereas later the efferent vessels connected directly to the choroidal venous system. The study of such plastic casts enables more accurate assessment of some aspects of the vascular architecture of the SRN frond.

Experimental subretinal neovascularization in the monkey. Permeability of new vessels.

The clinical appearance, fine structure, and permeability to horseradish peroxidase and fluorescein of subretinal neovascularization (SRN) in monkeys was correlated at various stages of vessel development: early (active leaking), intermediate (slightly leaking), and regressive (nonleaking). The degree of SRN permeability correlated well with the presence of endothelial cell fenestrations. The substantial changes in the fine structure and permeability of SRN during maturation can account for the different clinical manifestations. It is thus apparent that the time of morphologic correlation must be considered when studying a dynamic evolving process, such as SRN.

Novel mechanism by which hemoglobin induces constriction of cerebral arteries.

Since oxyhemoglobin (OxyHb) is implicated in the pathogenesis of cerebral vasospasm, we have investigated the role of protein tyrosine phosphorylation in OxyHb-mediated signalling in canine cerebral arteries and cultured canine cerebrovascular smooth muscle cells. OxyHb produced a contraction of basilar artery preparations, which was reversed by genistein, an inhibitor of tyrosine kinases, and PD098059, an inhibitor of mitogen-activated protein kinase. In cerebrovascular smooth muscle cells, OxyHb induced tyrosine phosphorylation of 42, 46, 54-60 and 80-100 kDa proteins with a time-course which paralleled the contractile action of OxyHb, suggesting that these events might be functionally linked. The 42 and 60 kDa proteins were immunologically related to the mitogen-activated protein kinase, extracellular signal regulated protein kinase (ERK2), and to p60c-Src (c-Src), respectively. The increase in protein tyrosine phosphorylation was attenuated by genistein, and the phosphorylation of the 42 kDa protein (ERK2) was inhibited by PD098059. These results suggest that OxyHb-mediated signalling utilizes a protein tyrosine kinase-based mechanism.

Changes of beta-actin mRNA expression in canine vasospastic basilar artery after experimental subarachnoid hemorrhage.

The aim of this study was to investigate whether vascular remodeling occurs during cerebral vasospasm after subarachnoid hemorrhage (SAH). Beta-actin mRNA expression and structural change of its 3' untranslated region (UTR) which are considered a non-specific marker for vascular remodeling, were examined by Northern analysis and polymerase chain reaction analysis in a canine basilar artery after experimental SAH. The changes in the area of tunica media in the basilar artery were also examined histopathologically. Increased beta-actin mRNA expression and its structural changes of 3' UTR in the vasospastic basilar artery were markedly seen 7 and 14 days after SAH accompanied by increased area of tunica media in the basilar artery. The results suggest that vascular remodeling occurs and takes part in the luminal narrowing during cerebral vasospasm.

Cerebrovascular disorders associated with von Recklinghausen's neurofibromatosis: a case report.

A 28-year-old woman with von Recklinghausen's neurofibromatosis (NF-1) had a huge hematoma in the left posterior nuchal region. Carotid and vertebral angiograms revealed marked stenosis at the C3 portion of the left internal carotid artery, slight moyamoya staining, occlusion of the left vertebral artery at the atlas level, and a right internal carotid artery aneurysm. The radiographic, clinical, and histological features of this case are discussed together with a review of 42 similar cases found in the literature.

Morphological changes of intraparenchymal arterioles after experimental subarachnoid hemorrhage in dogs.

OBJECTIVE: Morphological and microcirculatory changes in intraparenchymal vessels after subarachnoid hemorrhage (SAH) have not yet been fully clarified. We conducted this experimental study to investigate the serial morphological changes of intraparenchymal arterioles after SAH. METHODS: SAH was produced by injecting autologous arterial blood into the cisterna magna twice at 48-hour intervals in 30 dogs. The dogs were killed 3, 7, or 14 days after SAH, and then perfusion-fixed specimens of both anterior sylvian giri were obtained by using two methods. Microvascular corrosion casts produced by arterial injection of polyester resin were examined using scanning electron microscopy, and the widths of 40 arterioles of each animal were measured. Sectioned slices from the brain surface to 500 microns deep were examined by light microscopy, and external diameter, internal diameters, and wall thickness of the arterioles at depths of 50, 200, and 500 microns from the brain surface were morphometrically evaluated in 40 arterioles of each animal. In control animals receiving cisternal injections of mock cerebrospinal fluid (n = 10) and in healthy control animals (n = 10), the same examination and evaluation were performed. RESULTS: Corrosion casts of arterioles showed tapered narrowing with folding after SAH, and the width of the arterioles significantly decreased 3 and 7 days after SAH (P < 0.01). Morphometric examination by light microscopy showed a significant decrease of internal diameter of arterioles associated with a significant increase of wall thickness at any depth from the brain surface 3 and 7 days after SAH (P < 0.05 or P < 0.01). These findings improved 14 days after SAH. Control animals receiving cisternal injections of mock cerebrospinal fluid showed no significant differences compared with healthy control animals. CONCLUSION: These results suggest that constriction of intraparenchymal arterioles occurs after SAH and may contribute to delayed cerebral ischemia.

Antisense preproendothelin-oligoDNA therapy for vasospasm in a canine model of subarachnoid hemorrhage.

OBJECT: The purpose of this study is twofold: 1) to test antisense genetic techniques used in the prevention of cerebral vasospasm in a canine model of subarachnoid hemorrhage (SAH), targeting the endothelin-1 (ET-1) gene; and 2) to determine if fibrinolysis of subarachnoid clot with recombinant tissue plasminogen activator (rtPA) could enhance the effect of antisense treatment. METHODS: A total of 39 dogs were studied in this experiment. Placebo (six animals), rtPA (six animals), antisense preproET-1 oligodeoxynucleotide (ASOD; five animals), or rtPA plus ASOD (combined treatment; six animals) was injected into the cisterna magna 30 minutes after a second SAH was induced on the 2nd day of the experiment. The animals were observed until Day 7, when they underwent follow-up angiography and then were killed; their basilar arteries were removed for analysis. Control animals included in this study (two animals in each group) received placebo, rtPA, ASOD, or rtPA plus ASOD without induction of SAH, or rtPA with mismatched (nonsense) preproET-1 oligodeoxynucleotide following SAH. Six additional dogs were analyzed earlier following SAH. Dogs that received placebo developed severe vasospasm (51+/-8% of baseline caliber). Administration of ASOD alone resulted in a mild reduction in vasospasm (64+/-13% of baseline caliber) and rtPA alone resulted in a moderate reduction in vasospasm (81+/-5% of baseline caliber); however, the combined therapy of rtPA plus ASOD almost completely prevented vasospasm (95+/-6%, of baseline caliber), which was significantly different from all other groups (p < 0.05). Morphological analysis of the basilar arteries yielded results similar to angiography with respect to vasospasm severity. The ASOD treatment combined with rtPA resulted in reduced ET-1 expression, as demonstrated by immunohistochemical staining of the arteries, and reduced preproET-1 levels on Day 4, as measured by reverse transcription-polymerase chain reaction. Nonsense DNA sequences had no effect on the vessels. CONCLUSIONS: Antisense preproET-1 oligodeoxynucleotide treatment, when combined with clot lysis caused by rtPA, reduced vasospasm in the canine model of SAH, and this effect appeared to be related to reduced ET-1 synthesis. The results of this experiment support a causative role for ET-1 early in the course of vasospasm development in dogs. The apparent additive therapeutic effects of antisense and fibrinolytic treatments could be due to clot lysis, which allows better delivery of oligodeoxynucleotides to arteries within the subarachnoid space.

Chicamycin, a new antitumor antibiotic. II. Structure determination of chicamycins A and B.

Structures of chicamycins A and B have been determined from a series of chemical degradation studies coupled with spectroscopic analysis. Chicamycin A is 2(S),11(R), 11a (S)-1,2,3,10, 11, 11a -hexahydro-2,8-dihydroxy-7,11-dimethoxy-5H-pyrrolo-[2,1-c] [1,4]-benzodiazepin-5-one, and chicamycin B is 2(S), 11a (S)-1,2,3, 11a -tetrahydro-2,8-dihydroxy-7 -methoxy-5H-pyrrolo-[2,1-c][1,4]-benzodiazepin-5-one which is the demethanol form of chicamycin A. The structure of chicamycin B is closely related to that of neothramycin , differing only in the position of a hydroxyl substituent on the pyrrolidine ring.

BMY-28190, a novel antiviral antibiotic complex.

BMY-28190, an antibiotic complex active against herpes simplex virus type 1 (HSV-1) was produced by the cultured broth of Streptoalloteichus hindustanus sp. nov., a producing strain of tallysomycins A and B. The antibiotic complex was recovered from the broth with Amberlite IRC-50 resin and separated from the coproduced tallysomycins and nebramycins by a series of chromatographies. BMY-28190 exhibited weak inhibitory activity toward Gram-positive and Gram-negative bacteria and strong inhibitory activity toward HSV-1. Structural studies disclosed that BMY-28190 is a novel complex of gamma-poly-D-alpha, gamma-diaminobutyric acids with an average MW of 5,130.

Sultriecin, a new antifungal and antitumor antibiotic from Streptomyces roseiscleroticus. Production, isolation, structure and biological activity.

Streptomyces roseiscleroticus L827-7 (ATCC 53903) produced a novel antifungal and antitumor antibiotic, sultriecin. It exhibited in vitro antifungal activity and potent in vivo antitumor activity against P388 and L1210 leukemias, and B16 melanoma. Sultriecin is composed of several unique structural units; a conjugated triene, an alpha,beta-unsaturated delta-lactone, and a sulfate functionality.

Dynemicins, new antibiotics with the 1,5-diyn-3-ene and anthraquinone subunit. I. Production, isolation and physico-chemical properties.

Dynemicin A, a novel antibiotic containing the bicyclo[7.3.1]-1,5-diyn-3-ene and 1,4,6-trihydroxyanthraquinone functionalities, was isolated from the culture broth of Micromonospora chersina sp. nov. M956-1. The antibiotic exhibited potent in vitro antibacterial and cytotoxic activity, and in in vivo, it cured mice from lethal Staphylococcus aureus infection and prolonged survival time of mice inoculated with murine tumors. Three satellite components, dynemicins L, M and N, were also isolated from the culture broth and chemically characterized.

Synthesis and antifungal activities of pradimicin A derivatives modification of the alanine moiety.

Chemical modifications of the carboxyl group in the alanine moiety of pradimicin A were performed and in vitro and in vivo antifungal activities of the derivatives were examined in comparison with those of pradimicin A. The amide derivatives showed activities comparable to pradimicin A, indicating that the free carboxyl group can be modified without impairing the antifungal activity.

BBM-928, a new antitumor antibiotic complex. III. Structure determination of BBM-928 A, B and C.

Structures of antitumor antibiotics BBM-928 A, B and C have been determined. They are cyclic decadepsipeptides containing 3-hydroxy-6-methoxyquinaldic acid as a chromophore. Two amino acids, not found in nature, L-beta-hydroxyl-N-methylvaline and trans-(3S,4S)-4-hydroxy-2,3,4,5-tetrahydropyridazine-3-carboxylic acid, were identified as structural constituents of the antibiotic. In gross structure, BBM-928 resembles the echinomycin group of antibiotics which are cyclic octadepsipeptides having a quinoxaline chromophore, but BBM-928 differs from the latter group by virtue of the lack of a sulfur-containing cross linkage.

Pradimicins A, B and C: new antifungal antibiotics. I. Taxonomy, production, isolation and physico-chemical properties.

New antifungal antibiotics, pradimicins A, B and C were isolated from the culture broth of actinomycete strains proposed as Actinomadura hibisca. They are orange to red pigments containing a benzo[a]naphthacenequinone chromophore substituted with a D-alanine, an aminosugar and a D-xylose (pradimicins A and C).

Maduropeptin, a complex of new macromolecular antitumor antibiotics.

Maduropeptin, a complex of new macromolecular antitumor antibiotics, is a metabolite of Actinomadura madurae H710-49. The active components maduropeptins A1, A2 and B are acidic chromopeptides with MW of around 22,500 and composed of 14 types of amino acids and an unstable chromophore. The antibiotics are active in vitro against Gram-positive bacteria and highly cytotoxic to tumor cells. They produced significant prolongation of survival time of mice implanted with P388 leukemia and B16 melanoma.

Studies on the mode of antifungal action of pradimicin antibiotics. II. D-mannopyranoside-binding site and calcium-binding site.

Based on the structure-activity relationship data of BMY-28864 and related pradimicin derivatives, the calcium salt-forming ability and the D-mannopyranoside-specific visible absorption maximum shift of BMY-28864 were analysed in the ternary complex formation of BMY-28864 with D-mannopyranoside and calcium. The free C-18 carboxyl group of BMY-28864 was proved to be the sole site for binding to calcium, while no hydroxyl groups of the aglycone were involved in calcium salt formation. The stereospecific D-mannopyranoside-recognizing ability of BMY-28864 was completely abolished by removal of the C-5 disaccharide moiety, and, more particularly, of the C-5 thomosamine moiety. Close relationship of these findings with the antifungal action was also supported by the in vitro antifungal assay and the potassium leakage induction test.