Evidence for an activating effect of tabernanthine on rat brain catecholamine synthesis and elimination

Tabernanthine increased the synthesis and elimination of catecholamines (CA) in the striatum and the rest of the brain, but not in the hypothalamus. These data provide evidence that tabernanthine may activate CA turnover of some brain structures by acting at 2 steps of the metabolic pathway. The results are discussed in relation to a central stimulating action and a hypoxia antagonistic effect of this drug.     

Why isPyrrhocoris apterus insensitive to precocene II?

Summary Precocene II (P II) was applied to the adult females of 2 Pyrrhocorid bugs —Pyrrhocoris apterus (insensitive to P II) andDysdercus cingulatus (sensitive to P II)-subjected to allatectomy and intraspecific or interspecific reimplantations of corpus allatum (CA). The failure of P II to inhibit ovarian development inP. apterus appears to be caused by both a low sensitivity to P II of the CA itself and unknown anti-precocene mechanisms outside the CA.Precocene II was kindly supplied by Zoecon.     

早期营养不良对SD大鼠海马AchE和ChAT表达的影响

目的探讨生命早期营养不良对21天雄性sD大鼠中枢AchE和ChAT的影响。方法从妊娠晚期到哺乳期末给予母鼠半量饲料,造成子鼠营养不良,取哺乳期末雄性子鼠脑海马组织进行测量。结果免疫组化结果示：实验组海马CA3区ChAT光密度低于对照组（P〈0．05）,在CA!区无差异（P〉0．05）;而两纽间CAl和CA3区AchE光密度均无差异（P〉0．05）;RT—PCR示：实验组海马ChAT、AchEmRNA少于对照组（P〈0．05）。结论早期营养不良能导致子鼠海马及中枢胆碱能系统发育障碍,可能会影响成年后大鼠学习记忆能力。     

In vivo inactivation of denervated corpora allata by precocene II in the bug,Oncopeltus fasciatus

Summary Transection of the nervous connections between the brain and the corpus allatum (CA) inOncopeltus fasciatus does not alter the susceptibility of the CA to precocene II in vivo.The authors wish to thank Patricia Ferugia for rearing the insects; Dr D. Soderlund, Department of Entomology, New York State Agricultural Experiment Station for helpful discussions; and Dr A.O. Lea, Department of Entomology, University of Georgia for technical advice. To whom reprint requests should be addressed     

盐酸戊乙奎醚对大鼠感染性脑水肿AQP4表达的影响

目的：研究盐酸戊乙奎醚对感染性脑水肿保护作用的机制。方法：采用左颈内动脉注射脂多糖复制大鼠感染性脑水肿模型,将84只雄性SD大鼠随机分为对照组（C组）、水肿组（I组）、盐酸戊乙奎醚治疗组（P组）。检测6h、12h、24h、48h时各组大鼠脑组织含水量、病理形态;脑组织SOD活性、MDA含量;免疫组化法及RT—PCR法检测AQP4蛋白分布与AQP4mRNA含量。结果：（1）与C组相比,I组、P组脑含水量、MDA含量均升高,同时SOD活性、AQP4蛋白、AQP4mRNA表达均减少（P〈0．01）。与对应时间点P组相比,I组脑含水量、MDA含量均升高,同时SOD活性、AQP4蛋白、AQP4mRNA表达均减少,于24h达高峰,48h仍在较高水平（P〈0．01）。（2）脑组织光镜检查：I组大鼠脑组织损伤严重,P组损伤明显减轻。结论：盐酸戊乙奎醚能在一定程度上可减轻感染所致的脑组织损伤,上调AQP4表达,对脑水肿有一定治疗作用,其机制可能与抗氧化作用有关。     

A recombinant dromedary antibody fragment (VHH or nanobody) directed against human Duffy antigen receptor for chemokines

Fy blood group antigens are carried by the Duffy antigen receptor for chemokines (DARC), a red cells receptor for Plasmodium vivax broadly implicated in human health and diseases. Recombinant VHHs, or nanobodies, the smallest intact antigen binding fragment derivative from the heavy chain-only antibodies present in camelids, were prepared from a dromedary immunized against DARC N-terminal extracellular domain and selected for DARC binding. A described VHH, CA52, does recognize native DARC on cells. It inhibits P. vivax invasion of erythrocytes and displaces interleukin-8 bound to DARC. The targeted epitope overlaps the well-defined DARC Fy6 epitope. K _D of CA52?CDARC equilibrium is sub-nanomolar, hence ideal to develop diagnostic or therapeutic compounds. Immunocapture by immobilized CA52 yielded highly purified DARC from engineered K562 cells. This first report on a VHH with specificity for a red blood cell protein exemplifies VHHs?? potentialities to target, to purify, and to modulate the function of cellular markers.     

α-d-glucosidase in normal and leukemic lymphocytes

Zusammenfassung Der einfache Nachweis von -d-Glukosidase in leukämischen Lymphozyten gelang spektrophotometrisch. Dies lässt darauf schliessen, dass ein Enzymmangel nicht Ursache für die Glykogenspeicherung dieser Zellen sein kann. Es scheint sich um eine Ansammlung von glykolytischen Zwischenprodukten und nicht um einen Defekt der Glykogenolyse zu handeln.

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Supported by U.S.P.H.S. Research Grant No. CA 07000 and U.S.P.H.S. Training Grant No. 5 T1 CA5159.

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Work done as a U.S.P.H.S. Postdoctoral Research Fellow in hematology.

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Recipient of U.S.P.H.S. Career Development Award 1-K3-CA-8371.     

Effects of progesterone and estradiol benzoate on superoxide dismutase activity in the brain of male rats

The activities of mitochondrial, manganese-containing superoxide dismutase (MnSOD) and cytoplasmic, copper-zinc-containing superoxide dismutase (CuZnSOD) were measured in subcellular fractions of whole brain homogenates prepared from intact and gonadectomized (GDX) male rats, untreated or treated subcutaneously (sc) with a single dose of 2 mg progesterone (P) and/or 5 g estradiol benzoate (EB). Neither MnSOD nor CuZnSOD was affected by the removal of the testes. Similarly, CuZnSOD activity was steady following systemic administration of P and/or EB to intact and GDX animals 2 h or 24 h prior to sacrifice. On the other hand, both P and EB suppressed MnSOD in the brain of either intact or GDX rats. These results suggest involvement of P and EB in the control of MnSOD activity in the brain of male rats.     

Dithiols simulate endotoxin in theLimulus reaction

Summary Dithiothreitol, dithioerythritol and bacterial lipopolysaccharides increase optical absorbance and clotLimulus lysate. Purification of dithiothreitol from possible endotoxin contamination by vacuum sublimation or chromatography does not abolish the reaction with lysate. The dithiols reported active here represent the smallest molecules capable of simulating endotoxin in theLimulus test.Acknowledgments. This investigation was supported by grant No. P30 14194 and CA 12635, awarded by the National Cancer Institute, Dhew.     

异丙酚对大鼠内毒素脑损伤STAT3表达的影响

目的 研究异丙酚对大鼠内毒素脑损伤中信号转导子与转录激活子-3( STAT3)表达的影响,探讨异丙酚在脑损伤中的保护作用及其机制.方法 健康清洁级SD大鼠72只,雌雄不限,体重220～ 250 g,随机分为3组(n=24):L组(内毒素组)和LP组(内毒素+异丙酚组)经颈内动脉注射内毒素200 μg建立大鼠内毒素脑损伤模型,C组(对照组)经颈内动脉注射等量生理盐水,LP组颈内动脉注射内毒素后即予异丙酚100 mg/kg剂量腹腔注射.3组分别于6、12、24和48h随机处死6只大鼠,取额叶皮质,检测脑组织含水量,免疫组织化学检测P-STAT3、NF-κB和iNOS表达水平的变化,Western blot法检测大鼠内毒素脑损伤后P-STAT3蛋白表达水平的变化.结果 与C组相比,L组、LP组各时间点脑组织含水量、P-STAT3、NF-κB和iNOS表达增加(P ＜0.05,P＜0.01);与L组比较,LP组各时间点脑含水量、P-STAT3、NF-κB和iNOS表达明显减少(P＜0.05,P＜0.01).结论 异丙酚可减轻大鼠内毒素性脑损伤,机制可能与抑制脑组织磷酸化STAT3、NF-κB和iNOS表达水平上调,进而减轻炎性反应有关.     

Increased incidence of lymphomas in thymectomized Mice - evidence for an immunological theory of aging

Zusammenfassung Bei einem Mäusestamm mit hoher Rate spontaner Retikulosarkome wird gezeigt, dass die Tumoren bei neonatal thymektomierten Tieren signifikant rascher und häufiger auftreten.

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Supported by U.S.P.H.S. grants No. CA06519 and No. AM12151     

The preparation of metabolically active suspensions of mouse liver cells

Zusammenfassung Einfache und schnelle Methode zur Isolierung freier Mäuse-Leberzellen. Freie Hepatozyten (bis 50% des Gewebes) zeigen so aktiven Stoffwechsel.

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This work was supported by grant No. CA05172 of the National Cancer Institute, U.S.P.H.S.     

Treatment of spontaneous murine lymphomas with syngeneic lymphoid cells

Summary Syngeneic thymus grafts and spleen cells were administered to thymectomized and intact (C57BL/1XA)F₁ mice with spontaneous lymphomas. Their life span was prolonged significantly compared to untreated tumor-bearing controls. Dramatic clinical and histologic evidence of tumor regression was observed.Supported by US P.H.S. grants Nos AM12151 and CA 15500.     

Evidence for suppression of Na-dependent Ca2+ efflux from rat brain synaptosomes by ovarian steroids in vivo

The possibility that intracellular Ca2+, which mediates neurotransmitter release, regulation of membrane permeability, microtubule polymerization and axonal transport, is influenced by gonadal steroids via a Na-Ca exchange mechanism was examined. The resting Ca2+ uptake into synaptosomes was measured using crude synaptosomal pellets (P2 fraction), isolated from the brain stem, mesencephalic reticular formation (MRF), nucleus caudatus (NC) and the hippocampus of intact, long-term ovariectomized (OVX) and OVX plus progesterone (P) or estradiol-17 beta benzoate (EB) treated adult female rats. Irrespective of the brain structure investigated, the uptake was 1) markedly increased in synaptosomes from OVX animals in comparison to intact controls, and 2) reduced to near control values in synaptosomes from OVX rats treated s.c. with a single dose of 2 mg P or 5 micrograms EB. Since Ca2+ influx into synaptosomes was shown earlier to depend on external sodium concentration, which was the same in all experiments described in this work, the results obtained indicate that ovarian steroids modulate basal synaptic activity in the rat brain by suppressing Na-dependent Ca2+ efflux from the nerve cell.     

Control of corpus allatum activity inDiploptera punctata: roles of the pars intercerebralis and pars lateralis

Summary Control of the corpora allata (CA) ofDiploptera punctata is maintained by at least 2 factors. The glands are directly inhibited by an allatostatin arriving at the CA via the nervi corporis cardiaci I (NCC I). Destruction of the putative source (median neurosecretory cells, MNC) of the allatostatin by radio-frequency (RF) cautery relieved the inhibition imposed on the CA of virgin females, and the glands became active. Similarly, destruction of the lateral neurosecretory cells (LNC) also relieved the inhibition. We propose that the LNC stimulated the MNC to release allatostatin. RF-cautery did not result in the activation of CA of pregnant or ovariectomized females. Activation of the CA may therefore require not only absence of the inhibitory factor but also the presence of a stimulatory one (perhaps from the ovary).     

Identification of in vitro release products of corpora allata in female and male loreyi leafworms,Leucania loreyi

The in vitro release of juvenile hormones (JH) by female, and of JH acids (JHA) by male corpora allata (CA) ofLeucania loreyi was identified by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). Separation and quantification were accomplished by HPLC and GC, respectively. JH II and JH III were the major components released by CA of females. Four JHA analogues were identified as the release products of male CA, i.e. JHA III, Iso-JHA II, JHA II and JHA I. JHA III and Iso-JHA II were reported for the first time as the major release products of CA of adult male Lepidoptera. Iso-JHA II is a new member of the insect juvenile hormone analogue family.     

Resolution of small G1 and G2 populations of L1210 leukemia by flow microfluorometric analysis aided by velocity sedimentation

Summary L1210 leukemic cells grown in vitro were subjected to kinetic analysis using a flow microfluorometer. A single broad peak was found for the DNA content distribution if unfractionated cells were used; prior fractionation using lg velocity sedimentation allowed the separation of small peaks with smaller (G₁) and larger (G₂) DNA contents from the dominant S phase peak with intermediate DNA content.This work was supported by grant number 5P01CA13053 awarded by the National Cancer Institute, DHEW USA, and by grant num ber RBI 76-1 from the Queen Wilhelmina Fund, The Netherlands.     

Effects of constitutively active GTPases on fibroblast behavior

The GTP-binding proteins RhoA, Cdc42 and Rac1 regulate the organization and turnover of the cytoskeleton and cell-matrix adhesions, structures bridging cells to their support, and translating forces, external or generated within the cell. To investigate the specific requirements of Rho GTPases for biomechanical activities of clonal cell populations, we compared side-by-side stable lines of human fibroblasts expressing constitutively active (CA) RhoA, Cdc42 or Rac1. There was no marked effect of any CA GTPase on cell adhesion to different extracellular matrix proteins. Cell spreading was CA Rho GTPase specific and independent of the extracellular matrix proteins allowing adhesion. Mechanical properties were dramatically restricted by CA RhoA on bi- and in tri-dimensional surroundings, were boosted by CA Rac1 on bi-dimensional surroundings only, and were not or marginally affected by CA Cdc42. In conclusion, the action of Rho GTPases appears to depend on the task cells are performing. Received 12 September 2005; received after revision 5 October 2005; accepted 1 November 2005     

Immunosuppressive effect of a mouse placenta fraction on H-2 incompatible split heart allografts

Summary A soluble placenta fraction from mice (A.CA) mated with H-2 histoincompatible males (A/Sn) significantly prolonged the survival of heterotopic A/Sn heart transplants in A.CA recipients. No prolongation of A/Sn heart graft survival was obtained with the corresponding A.CA placenta fraction after A.CA × A.CA mating.The work was supported by the Danish Medical Research Council (Project No. 512-3088).     

On the mechanism of modification of radiation effect by dimethyl sulfoxide

Zusammenfassung Es wurde die früher in vivo beobachtete dichotome Wechselwirkung zwischen Dimethylsulfoxid (DMSO) und Röntgenstrahlen in vitro an einem System von Säugetierzellen untersucht. Wird 3% DMSO vor der Bestrahlung zugefügt, so wirkt es als Radioprotektor, gleichgültig, ob unmittelbar nach der Bestrahlung entfernt oder während der Reparationszeit belassen. Das Überleben wird auffallend erhöht, wenn eine Konzentration von 15% DMSO während der Bestrahlung vorhanden ist oder aber unmittelbar danach entfernt wird. Verbleibt der Wirkstoff während der Reparationszeit, so kommt es zu einer drastischen Herabsetzung der Überlebensquote.

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Supported in part by N.I.H. Grants No. 5 P02 CA10438-02 and No. 5 T01 CA5184-03.