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1.
We have isolated the delta-globin gene of the New-World spider monkey,
Ateles geoffroyi, and compared its nucleotide sequence with those of other
primate delta- and beta-globin genes. Among primate delta-globin genes, the
rate of nonsynonymous substitutions is much less than the rate of
synonymous substitutions. This suggests that primate delta- globin genes
may remain under evolutionary conservation, perhaps because hemoglobin A2
has an as yet unknown physiological importance.
相似文献
2.
Kalpana Mujoo Ralph A. Reisfeld Lawrence Cheung Michael G. Rosenblum 《Cancer immunology, immunotherapy : CII》1991,34(3):198-204
Summary Monoclonal antibody 14G2a (anti-GD2) reacts with cell lines and tumor tissues of neuroectodermal origin that express disialoganglioside GD2. mAb 14G2a was coupled to the ribosome-inactivating plant toxin gelonin with the heterobifunctional cross-linking reagentN-succinimidyl-3(2-pyridyldithio)propionate. The activity of the immunotoxin was assessed by a cell-free translation assay that confirmed the presence of active gelonin coupled to 14G2a. Data from an enzyme-linked immunosorbent assay demonstrated the specificity and immunoreactivity of the 14G2a-gelonin immunotoxin, which was identical to that of native 14G2a. Assays for complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) revealed that these functional properties of the native 14G2a antibody were also preserved in the 14G2a-gelonin immunotoxin. The gelonin-14G2a immunotoxin was directly cytotoxic to human melanoma (A375-M and AAB-527) cells and was 1000-fold more active than native gelonin in inhibiting the growth of human melanoma cells in vitro. The augmentation of tumor cell killing of 14G2a-gelonin immunotoxin was examined with several lysosomotropic compounds. Chloroquine and monensin, when combined with 14G2a-gelonin immunotoxin, augmented its cytotoxicity more than 10-fold. Biological response modifiers such as tumor necrosis factor and interferon and chemotherapeutic agents such as cisplatinum andN,N-bis(2-chloroethyl)-N-nitrosourea (carmustine) augmented the cytotoxicity of 14G2a-gelonin 4- to 5-fold. The results of these studies suggest that 14G2a-gelonin may operate directly by both cytotoxic efforts and indirectly by mediating both ADCC and CDC activity against tumor cells; thus it may prove useful in the future for therapy of human neuroectodermal tumors.Research conducted, in part, by the Clayton Foundation for Research 相似文献
3.
Biochemical pathways in prokaryotes can be traced backward through evolutionary time 总被引:10,自引:0,他引:10
For the first time, a credible prokaryotic phylogenetic tree is being
assembled by Woese and others using quantitative sequence analysis of
oligonucleotides in the highly conservative rRNA. This provides an
evolutionary scale against which the evolutionary steps that led to the
arrangement and regulation of contemporary biochemical pathways can be
measured. This paper presents an emerging evolutionary picture of aromatic
amino acid biosynthesis within a large superfamily assemblage of
prokaryotes that is sufficiently developed to illustrate a new perspective
that will be applicable to many other biochemical pathways.
相似文献
4.
5.
James D. Pancook Jürgen C. Becker Stephen D. Gillies R. A. Reisfeld 《Cancer immunology, immunotherapy : CII》1996,42(2):88-92
A major problem in the treatment of solid tumors is the eradication of established, disseminated metastases. Here we describe
an effective treatment for established experimental hepatic metastases of human neuroblastoma in C. B.-17 scid/scid mice. This was accomplished with an antibody-cytokine fusion protein, combining the unique targeting ability of antibodies
with the multifunctional activity of cytokines. An anti-(ganglioside GD2) antibody (ch14.18) fusion protein with interleukin-2
(ch14.18-IL2), constructed by fusion of a synthetic sequence coding for human interleukin-2 (IL-2) to the carboxyl end of
the Cγ1 gene of ch14.18, was tested for its therapeutic efficacy against xenografted human neuroblastoma in vivo. The ch14.18-IL2
fusion protein markedly inhibited growth of established hepatic metastases in SCID (severe combined immunodeficiency) mice
previously reconstituted with human lymphokine-activated killer cells. Animals treated with ch14.18-IL2 showed an absence
of macroscopic liver metastasis. In contrast, treatment with combinations of ch14.18 and recombinant IL2 at dose levels equivalent
to the fusion protein only reduced the tumor load. Survival times of SCID mice treated with the fusion protein were more than
double that of control animals. These results demonstrate that an immunotherapeutic approach using a cytokine targeted by
an antibody to tumor sites is highly effective in eradicating the growth of established tumor metastases.
Received: 7 November 1995 / Accepted: 15 December 1995 相似文献
6.
In Drosophila pseudoobscura, the amylase (Amy) multigene family is
contained within a series of inversions, or gene arrangements, on the third
chromosome. The Standard (ST), Santa Cruz (SC), and Tree Line (TL)
inversions are central to the phylogeny of arrangements, and have clusters
of other arrangements derived from them. The gene arrangements belonging to
each of these three clusters have a characteristic number of Amy genes,
ranging from three in ST to two in SC to one in TL. This distribution
pattern can reflect a history of either duplications or deletions, although
the data available in the past did not permit a decision between these
alternatives. We provide unambiguous evidence that three Amy genes were
present before the divergence of the ST, SC, and TL arrangements. Thus, the
current status of the Amy multigene family is the result of deletions in
the TL and SC arrangements, which created three new pseudogenes: TL
Amy2-psi, TL Amy3-psi, and SC Amy3- psi. Analysis of pseudogene sequences
revealed that, in the SC and ST arrangements, pseudogene evolution has been
retarded, most likely due to the homogenization effect of gene conversion.
Finally, by determining the original copy number, we have reconstructed the
evolutionary history of the Amy multigene family and linked it with the
evolution of the central gene arrangements.
相似文献
7.
8.
The application of sensory methodology for measuring deodorizing effect of an air conditioner equipped with electric plasma was introduced. Deodorizing effect was measured using chemical and sensory methods at different time (0, 30 and 60 min) and mode (control, blowing and cooling) of an air conditioner. Smoke from a roll of cigarette in a closed room was used as a source of odor and the concentrations of acetic acid and ammonia were measured as odorous chemical components. As one of the sensory methods triangle test was used and as a first step to obtain deodorizing effects by triangle test, the threshold of each panelist was obtained as the log dilution ratio of odor concentration at which the difference from odorless air was detected. The odor concentration at each time and mode was calculated using the threshold of the panel and the deodorizing effect was obtained on the basis of the odor concentration. In addition to a triangle test, scaling methods such as category scaling or magnitude estimation were used to measure deodorizing effect of an air conditioner. Deodorizing effects by scaling methods were calculated based on odor intensity with time at each mode. The regression analysis was done between the efficacy of deodorizing effect by sensory test and those by acetic acid and ammonia, the R2 values of the regression equations for triangle test, category scale, and magnitude estimation were 0.84, 0.72 and 0.69, respectively. Deodorizing effect by triangle test explained the decrease of acetic acid and ammonia better than those by category scaling or magnitude estimation while high cost and time consuming labor involved in triangle tests reduced the merit. The results of this study demonstrated that various sensory methods could be used to measure deodorizing effect of air conditioners and further researches on fast and reliable methods are needed to establish the official procedures. 相似文献
9.
10.
Martina M. Uttenreuther-Fischer Chuin-Sheng Huang Ralph A. Reisfeld Alice L. Yu 《Cancer immunology, immunotherapy : CII》1995,41(1):29-36
A phase I trial of a murine anti-ganglioside (GD2) monoclonal antibody (mAb) 14G2a was conducted in 14 neuroblastoma patients and 1 osteosarcoma patient to assess its safety, toxicity and pharmacokinetics in pediatric patients. The pharmacokinetics of mAb 14G2a were biphasic with at
1
2/
of 2.8±2.8 h and at
1
2/
of 18.3±11.8 h. In general,t
1
2/
was dose-dependent with a level of significance ofP=0.036, and it reached a plateau at doses of 250 mg/m2 or more. Overall the peak serum levels were dose-dependent atP<0.001. However, they demonstrated an abrupt increase between doses of 100 mg/m2 and 250 mg/m2. The latter two suggest a saturable mechanism for mAb elimination. In addition, peak serum concentrations were observed earlier at higher mAb doses, which indicates the achievement of a steady state. Thet
1
2/
of mAb 14G2a in children appears to be shorter than in adults. Furthermore, 2 patients demonstrated a considerable decrease int
1
2/
following retreatment with 14G2a. This was paralleled by high human anti-(mouse Ig) antibody levels. This study represents the first comprehensive analysis of murine mAb pharmacokinetics in children and will be useful in the future design of mAb therapy.This work was supported by grants from FDA, FD-R-000377 and NIH U10 CA 28439 and in part by a grant from the general Clinical Research Center program, MOI RR00827, of the National Center for Research Resources, National Institutes of Health. M. M. U.-F. and C.-S. H. were supported in part by a grant from the Children's Cancer Research Foundation, and R. A. R. was supported in part by NIH grant CA 42508 相似文献