用于婴儿母亲的新型手动吸乳器与微型电动吸乳器的功效比较研究

目的比较微型电动吸乳器(MEP)与设计操作更合科生理需求的新型手动吸乳器(MP)的功效.在产后8w,60例怀孕足月的哺乳母亲随意使用MP和MEP,每侧乳房10min.测量乳汁量、脂肪含量、乳汁流出方式.通过提问方式获得哺乳母亲对吸乳器的评价.当哺乳母亲以随意顺序使用吸乳器时,乳汁量与脂肪含量无显著差异.哺乳母亲对MP评价明显优于MEP,而且觉得MP更舒适,所以更乐于接受MP.保留MP比MEP的母亲明显增多.尽管MEP贵重,但MP显然更受哺乳母亲青睐.这种新型的、更接近生理操作的MP代表吸乳器技术的进步.     

Endogenous estrogen status, but not genistein supplementation, modulates 7,12-dimethylbenz[a]anthracene-induced mutation in the liver cII gene of transgenic big blue rats

A growing number of studies suggest that isoflavones found in soybeans have estrogenic activity and may safely alleviate the symptoms of menopause. One of these isoflavones, genistein, is commonly used by postmenopausal women as an alternative to hormone replacement therapy. Although sex hormones have been implicated as an important risk factor for the development of hepatocellular carcinoma, there are limited data on the potential effects of the estrogens, including phytoestrogens, on chemical mutagenesis in liver. Because of the association between mutation induction and the carcinogenesis process, we investigated whether endogenous estrogen and supplemental genistein affect 7,12-dimethylbenz[a]anthracene (DMBA)-induced mutagenesis in rat liver. Intact and ovariectomized female Big Blue rats were treated with 80 mg DMBA/kg body weight. Some of the rats also received a supplement of 1,000 ppm genistein. Sixteen weeks after the carcinogen treatment, the rats were sacrificed, their livers were removed, and mutant frequencies (MFs) and types of mutations were determined in the liver cII gene. DMBA significantly increased the MFs in liver for both the intact and ovariectomized rats. While there was no significant difference in MF between the ovariectomized and intact control animals, the mutation induction by DMBA in the ovariectomized groups was significantly higher than that in the intact groups. Dietary genistein did not alter these responses. Molecular analysis of the mutants showed that DMBA induced chemical-specific types of mutations in the liver cII gene. These results suggest that endogenous ovarian hormones have an inhibitory effect on liver mutagenesis by DMBA, whereas dietary genistein does not modulate spontaneous or DMBA-induced mutagenesis in either intact or ovariectomized rats.     

Supportive and Negative Responses in the Partner Relationship: Their Association with Psychological Adjustment Among Individuals with Cancer

This study examined the association between positive and negative aspects of spouse responses and psychological adjustment among 15S individuals with cancer. Two contextual variables, gender and disease-related functional impairment, were taken into account when examining the association between spouse responses and patient psychological distress and well-being. Results indicated that negative aspects of close relationships played a comparatively stronger role than positive aspects in their associations with both psychological distress and well-being. For negative spouse responses, patient gender did not moderate the effects of these responses upon psychological outcomes. For positive aspects of spouse support, both gender and functional disability moderated the association between spouse support and psychological outcomes. These findings are integrated with the general literature on positive and negative aspects of close relationships. Implications for clinical interventions are also discussed.     

The Pharmacokinetics of Recombinant Human Relaxin in Nonpregnant Women After Intravenous,Intravaginal, and Intracervical Administration

The pharmacokinetics of recombinant human relaxin (rhRlx) after intravenous (iv) bolus administration and the absorption of rhRlx after intracervical or intravaginal administration were determined in nonpregnant women. The study was conducted in two parts. In part I, 25 women received 0.01 mg/kg rhRlx iv. After a minimum 7-day washout period, these women were dosed intracervically (n = 10) or intravaginally (n = 15) with 0.75 or 1.5 mg rhRlx, respectively, in 3% methylcellulose gel. Part II was a double-blind, randomized, three-way crossover study in 26 women. At 1-month intervals, each woman received one of three intravaginal treatments consisting of 0 (placebo), 1, or 6 mg rhRlx in 3% methylcellulose gel. The serum concentrations of relaxin following iv administration were described as the sum of three exponentials. The mean (±SD) initial, intermediate, and terminal half-lives were 0.09 ± 0.04, 0.72 ± 0.11, and 4.6 ± 1.2 hr, respectively. Most of the area under the curve was associated with the intermediate half-life. The weight-normalized clearance was 170 ± 50 mL/hr/kg. The observed peak concentration was 98 ± 29 ng/mL, and the weight-normalized initial volume of distribution was 78 ± 40 mL/kg, which is approximately equivalent to the serum volume. If central compartment elimination was assumed, the volume of distribution at steady state (V _ss/W) was 280 ± 100 mL/kg, which is approximately equivalent to extracellular fluid volume. V _ss/W could be as large as 1300 ± 400 mL/kg without this assumption. After intravaginal administration of the placebo gel, endogenous relaxin concentrations were evident (i.e., 20 pg/mL) in 9 of the 26 women (maximum concentrations, 23–234 pg/mL). A similar proportion of women (approximately 35–40%) exhibited measurable serum concentrations of relaxin following intravaginal rhRlx treatment; this proportion increased to 90% following intracervical rhRlx treatment. For both routes of administration, the maximum serum concentrations of relaxin were usually within the range of values observed for endogenous relaxin, suggesting that the absorption of rhRlx was minimal.     

Chemical conjugation of a novel antibody-interleukin 2 immunoconjugate agains t c-erbB-2 product

Objective To develop a new chemical method to produce a monoclonal antibody (MoAb) 520C9/recombinant human interleukin 2 (rhIL-2) conjugate. Methods MoAb 520C9 reactive with the protooncogene c-erbB-2 product P185 was chemically conjugated with rhIL-2 by using a simple two-step method.First, the rhIL-2 was activated by Sulfosuccinimidyl 4-［N-maleimidomethyl］ cyclohexane-1-carboxylate, a heterobifunctional linker, and N-succinimidyl s-acetylthioacetate was introduced onto 520C9.Then SATA on the 520C9 was reacted with the maleimide group on the activated rhIL-2 to generate 520C9-rhIL-2 immunoconjugate. Results The immunoconjugate retained the antigen binding activity compared to the respective native antibody as determined by an indirect live cell binding assay.The immunoconjugate also possessed IL-2 activity as measured by the standard CTLL-2 cells proliferation assay and the stimulation of human peripheral blood mononuclear cells (PBMCs) into lymphokine-activated killer cells. Conclusion Our method of conjugation of rhIL-2 to 520C9 preserves the binding activity of the antibody and the cytokine function of IL-2.This simple and efficient method of conjugation should be applicable to other types of MoAbs and recombinant cytokines.     

Misoprostol Partially Inhibits the Renal Scarring of Chronic Cyclosporine Nephrotoxicity

Chronic cyclosporine (CY) nephrotoxicity is a well-known complication of this immunosuppressive agent, which may, in part, be attributed to abnormalities in renal prostaglandin content. We utilized misoprostol (M), a prostaglandin E(1) analog, in a rat model of chronic CY toxicity at 7 and 28 days to determine effectiveness in prevention of the renal damage. After 7 days, there were no differences in weight change, creatinine clearance, or renal scarring in rats treated with vehicle (V), CY, or CY + M; however, renal procollagen alpha 1(I) mRNA levels were increased in CY versus V rats (p < 0.05). In contrast, after 28 days CY rats had significant reductions in weight gain, glomerular filtration rate, and renal blood flow with increases in renal scarring and procollagen alpha 1 (IV) mRNA levels (all p < 0.05 versus V). Addition of M resulted in partial but significant improvement in GFR, RBF, and procollagen alpha 1(IV) mRNA levels, with lessening of the renal scarring. Skin fibroblasts also were incubated with CY and M to assess impact on procollagen MRNA levels. CY augmented fibroblast procollagen mRNA levels which enhanced by a large dose of M, but inhibited with a moderate dose. These data suggest that M improves renal scarring induced by CY by hemodynamic and/or direct effects.     

Bioequivalence of Two Recombinant Human Growth Hormones in Healthy Male Volunteers after Subcutaneous Administration

The bioequivalence of recombinant human growth hormone (rhGH) (somatropin) and its N-methionyl variant (Met-hGH) [Protropin((R)) (somatrem for injection)] was determined in 42 healthy male volunteers (n = 21 per treatment) who were randomized to receive either protein by subcutaneous administration of 0.1 mg kg(minus sign1). Serum samples were collected over 24 h after the injection, and the concentration of human growth hormone (hGH) were determined by an immunoradiometric assay. Bioequivalence of the two proteins was assessed by determining whether the 90% confidence limits for the ratio of geometric means using logarithmically transformed AUC and C(max) parameters (log(10)AUC(0--24), log(10)AUC(0--infty infinity), and log(10)C(max)) were within the 80--125% range. The bioequivalence of the two treatments was also tested by calculating a bioequivalance index (xi(2)) that measured the difference between the two mean concentration-time profiles. The 90% confidence intervals for the ratios of the geometric means for AUC were within the prescribed 80--125% range for bioequivalence. The upper limit of the 90% confidence interval for the ratio of the geometric means for C(max) fell slightly outside the 125% criterion even though the geometric mean itself, 106.6%, was very close to the ideal of 100%. There was a larger standard error associated with C(max) than with the AUCs, and this marginally larger confidence limit for C(max) resulted more from the variance among the subject than to the difference in the means. In fact, the bioequivalence index, xi(2), was 0.075, indicating that the mean curves after rhGH and Met-hGH are essentially superimposable.     

Chromosome 11q13 markers and D-type cyclins in breast cancer

Summary One in six primary human breast cancers has DNA amplification centered on the cyclin D1 gene (CCND1) on chromosome 11q13. This genetic abnormality is preferentially associated with estrogen-receptor positive tumors and may define a sub-class of patients with an adverse prognosis. AlthoughCCND1 has the credentials of a cellular oncogene, being a target for chromosomal translocation and retroviral integration, the 11q13 amplicon encompasses several other markers andCCND1 is not the only candidate for the key gene on the amplified DNA. To assess their relative importance, we have constructed a physical map of the amplified DNA and compared the extent and frequency of amplification across the region. Since it is likely that the gene providing the selective force for amplification will be expressed at elevated levels, we have also examined expression of both RNA and protein. By these criteria, cyclin D1 remains the strongest candidate for the key oncogene on the amplicon and we are currently investigating the functional consequences of its over-expression.Presented by Gordon Peters at the 16th Annual San Antonio Breast Cancer Symposium, San Antonio TX, USA, November 4, 1993; Minisymposium on Molecular Genetics in Breast Cancer.