The ligand for c-kit, stem cell factor, stimulates the circulation of cells that engraft lethally irradiated baboons.

Recombinant human stem cell factor (SCF), the ligand for c-kit, has been shown to stimulate increased numbers of hematopoietic progenitor cells of multiple types to circulate in the blood of baboons, but it was not known if the cells stimulated to circulate by SCF contained cells capable of engrafting and rescuing lethally irradiated baboons. Peripheral blood mononuclear cells (PBMNC) were collected by leukapheresis from four untreated control baboons and from three baboons on the 10th or 11th day of treatment with SCF (200 micrograms/kg/d). All animals were transplanted with 1.00 to 1.04 x 10(8)/kg of cryopreserved autologous PBMNC after treatment with a single dose of 1,020 cGy total body irradiation (TBI). Three animals were transplanted with PBMNC that had been collected during SCF treatment, 24 to 38 days after the last dose of SCF. Rapid trilineage engraftment was documented by bone marrow biopsy in all three. The mean time to a total white blood cell count (WBC) > or = 500/microL, WBC > or = 1,000/microL, and an absolute neutrophil count (ANC) > or = 500/microL was 15 +/- 3 (mean +/- SD), 19 +/- 1, and 19 +/- 2 days, respectively. Two animals remain alive with stable engraftment more than 180 and 245 days posttransplant. The third died of sepsis 32 days posttransplant with a hypercellular marrow showing trilineage engraftment. The surviving animals were transfusion independent by 10 and 59 days posttransplant. Four control animals were transplanted with PBMNC collected in the absence of SCF stimulation. One was treated for 11 days with SCF (200 micrograms/kg/d) after PBMNC were collected. This animal was transplanted 25 days after the last dose of SCF. None of the four control animals engrafted and they died 13, 16, 28, and 38 days posttransplant with marrow aplasia. Treatment with SCF stimulates the circulation of cells that engraft and rescue lethally irradiated baboons. The characteristics of the transplantable cells present in the circulation are now amenable to direct study.     

Serogroup B meningococcal disease in the Norwegian armed forces: What can we learn from an inconclusive vaccine protection trial?

Military recruits serving in the armed forces were severelyaffected during the latest serogroup B meningococcal epidemicin Norway. The risk of developing systemic meningococcal disease(SMD) proved highest during the first 12 weeks of service. Adouble-blind, placebo-controlled protection trial with a meningococcalouter membrane vesicle vaccine took place between 1988 and 1991,but the number of proven SMD cases was too low to allow forany conclusions. However, the results of a parallel efficacystudy of the same vaccine among students in secondary school,cross-society examinations for asymptomatic throat carriageof meningococci and recent immunogenicity studies after two-and three-dose vaccination schedules, suggest that a basic immunizationof young teenagers followed by a booster injection at enrolmentwould contribute significantly to preventing SMD in the armedforces.     

鹿茸多肽的纯化和鉴定(英文)

应用凝胶过虑和离子交换层析等技术,从鹿茸(pilose antler or Cervus nipponTemminck)中分离纯化出一种多肽(peptide of pilose antler,PAP)。经高效液相色谱和N-末端氨基酸分析鉴定为单一多肽,氨基酸组成分析证明,PAP是由68个氨基酸组成,分子是为7200。药理研究证明,PAP对大鼠角叉菜胶性足肿胀具有明显的抑制作用并呈现良好的量—效关系。     

The interleukin-5 messenger RNA expression in a patient with idiopathic hypereosinophilic syndrome

Interleukin-5 has a specific role in various eosinophilic activities. It is the predominant cytokine produces by activated T-lymphocytes isolated from patients with idiopathic hypereosinophilic syndrome. We studied a young patient suffering from idiopathic hypereosinophilic syndrome who presented with Horner's syndrome, peripheral neuropathy and skin ulcers. The IL-5 gene expression by CD4⁺ T-lymphocytes and the peripheral eosinophil count were raised. The skin ulcers continued to deteriorate despite a swift reduction of the IL-5 gene expression and peripheral eosinophil count following systemic corticosteroid treatment. We suggest that peripheral eosinophilia may not be responsible for the damage in skin lesions and more aggressive treatment may be required.     

In-vitro activity of PD 131628, a new quinolone antimicrobial agent.

The in-vitro activity of PD 131628, the active metabolite of the prodrug PD 131112, was compared with that of ciprofloxacin and members of other groups of antimicrobial agents against 701 recent clinical isolates and strains with known mechanisms of resistance. The MIC90s of PD 131628 against the Enterobacteriaceae were between 0.008 and 0.5 mg/L; PD 131628 was one- to four-fold more active than ciprofloxacin against these strains and was four-fold more active than ciprofloxacin against Pseudomonas aeruginosa. Against the Gram-positive species tested, PD 131628 was two- to four-fold more active than ciprofloxacin, inhibiting all strains of Staphylococcus aureus and Streptococcus pneumoniae with 0.5 mg/L or less. PD 131628 was very active against Neisseria spp., Haemophilus influenzae and Moraxella catarrhalis, with MIC90s ranging from 0.004 to 0.008 mg/L. Organisms with decreased susceptibility to other quinolones had decreased susceptibility to PD 131628, but there was no cross-resistance between this class of antimicrobial and other classes. The protein binding of PD 131628 was at most 25% across a broad range of concentrations. The addition of 70% human serum had little effect on the MICs, but caused a two- to eight-fold increase in MBCs.     

Analysis of the effects of overexpression of metallothionein-I in transgenic mice on the reproductive toxicology of cadmium.

Exposure to low levels of cadmium reduces fertility. In male mice spermatogenesis is highly sensitive to cadmium, whereas in females the peri-implantation period of pregnancy is sensitive. To examine the potential roles of the cadmium-binding protein, metallothionein (MT), in the reproductive toxicology of cadmium, we examined a transgenic mouse strain that overexpresses metallothionein-I (MT-I). These mice had dramatically increased steady-state levels of MT-I mRNA and MT in the testes and in the female reproductive tract during the peri-implantation period of pregnancy, and this overexpression occurred in a cell-specific and temporally regulated manner similar to that of the endogenous MT-I gene. Transgenic and control males were injected with cadmium, and the histology of the testes was examined. An injection of 7.5 mumol Cd/kg had no effect on histology of the testes in either transgenic or control mice. In contrast, an injection of 10 mumol Cd/kg caused rapid changes in the histology of the testes and resulted in pronounced testicular necrosis in both control and transgenic mice. Female transgenic and control mice were mated and then injected with cadmium (30-45 mumol Cd/kg) on the day of blastocyst implantation (day 4). In both of these groups, injection of cadmium reduced pregnancy rate, and no dramatic protection was afforded by maternal and/or embryonic overexpression of MT. Thus, overexpression of MT-I does not significantly protect against either of these cadmium-induced effects on fertility.     

Pharmacokinetics and Inflammatory Fluid Penetration of Clinafloxacin

A single 200-mg dose of clinafloxacin was given orally to each of nine healthy male volunteers, and the concentrations of the drug were measured in plasma, cantharidin-induced inflammatory fluid, and urine over the following 24 h (48 h in the case of urine). The mean maximum concentration in plasma was 1.34 μg/ml at a mean time of 1.8 h postdose. The mean maximum concentration in the inflammatory fluid was 1.3 μg/ml at 3.8 h postdose. The mean elimination half-life of clinafloxacin in plasma was 5.65 h. The overall penetration into the inflammatory fluid was 93.1%, as assessed by determining the ratio of area under the concentration-time curves. Recovery of clinafloxacin in urine was 58.8% by 24 h and 71.8% by 48 h postdose.