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Biomedical subjects

D Klein

Publications and source records attributed to D Klein.

At least 181 records · Page 10Linked to original sources
PubMed1987

Acellular and whole-cell pertussis vaccines in Japan. Report of a visit by US scientists.

Since the introduction of acellular pertussis vaccines in Japan late in 1981, more than 20 million doses have been administered, mostly to children 2 years of age and older. Clinical studies indicate that mild local and febrile reactions are less frequent after administration of acellular pertussis vaccines than after whole-cell vaccines. Serious adverse events with sequelae occurred in 2-year-old children at approximately the same low rate during the period 1975 through August 1981, when whole-cell vaccines were used, and during August 1981 through 1984, when acellular vaccines were used exclusively. Five household contact studies have yielded vaccine efficacy estimates ranging from 78% to 92% in children 1 year of age or older. In addition, there has been a continuing decrease in reported pertussis incidence from the epidemic peak in 1979. Additional data on the safety and efficacy of acellular pertussis vaccines administered to infants would be useful in consideration of acellular pertussis vaccine licensure in the United States.

Child, Preschool↗
PubMed1987

Structural alterations in the long terminal repeat of an acquired mouse mammary tumor virus provirus in a T-cell leukemia of DBA/2 mice.

ML, a transplantable T-cell leukemia of DBA/2 mice, expresses the gag and env gene products of the murine mammary tumor virus (MuMTV). Analysis of the genomic DNA of ML cells using the restriction enzyme HindIII and hybridization with MuMTV-specific probes revealed that the ML cells contained two or more newly integrated MuMTV proviruses (ML-MuMTV). Further analysis of these proviruses with a combination of Mspl and Pstl enzymes showed that the long terminal repeat (LTR) (ML-MuMTV LTR) of the ML-MuMTV provirus(es) was structurally different from the LTRs of both exogenous and endogenous MuMTV proviruses of DBA/2 mice. In order to characterize the nature of the structural alterations in the ML-MuMTV LTR, we cloned a 4.0-kb HindIII fragment containing the 3' half of an acquired provirus. Sequence analysis of the ML-MuMTV LTR of this acquired provirus revealed a deletion of a 387-bp segment that maps between the 5' nucleotide 616 and the 3' nucleotide 1003 of the normal MuMTV LTR and duplication of a 102-bp fragment that mapped between 514 and 616. In addition to two point mutations in the direct repeat, the proviral ML-MuMTV LTR has also acquired 9- and 7-bp segments at the 5' and 3' sites of the duplicated 102-bp segment, respectively. Since direct repeats in the U3 regions of a number of LTRs have been found to be associated with enhancer function, we examined the enhancer function of the U3 region sequences of the ML-MuMTV LTR using enhancer-dependent transient expression assay of chloramphenicol acetyltransferase (CAT) gene in NIH 3T3 cells. Our studies have shown that the U3 region sequences of the rearranged ML-MuMTV LTR have the ability to enhance the expression of the CAT gene 12- to 15-fold more than the U3 region sequences from the normal MuMTV LTR. The presence of a direct repeat in the ML-MuMTV LTR and its ability to enhance the transcription of adjacent genes is analogous to the LTRs of certain murine leukemia viruses.

Animals↗
PubMed1987

Metabolism of ganglioside-amides in cultured human fibroblasts.

Metabolism of [3H]ganglioside derivatives GM3-amide and GM2-amide has been investigated in normal human skin fibroblasts. In a cell-free system the ganglioside analogues have been shown to enter biosynthetic pathways, their degradation, however, was curtailed at an early stage, as GM3-amide could not be hydrolysed by sialidase action. GM2-amide was susceptible to beta-hexosaminidase degradation yielding GM3-amide. When incorporated into fibroblasts [3H]GM2-amide was degraded to [3H]GM3-amide presumably in the lysosomes, and at the same time glycosylation to [3H]GD1a-monoamide took place most likely in the Golgi apparatus. [3H]GM3-amide, however, did not seem to reach the glycosylation sites in the Golgi apparatus. It could be detected in the lysosomes, where it was not degraded due to its sialidase resistance. From these results we conclude that in cells exogenously administered [3H]GM3-amide and [3H]GM2-amide both are directed to the lysosomes and that [3H]GM2-amide also reaches the Golgi apparatus. The synthesis of higher [3H]ganglioside-amides from incorporated [3H]GM2-amide can occur by direct glycosylation. [3H]GM3-amide, however, even if it reaches the Golgi compartment, does not enter the biosynthetic pathway.

Amines↗
PubMed1986

The assignment of chain specificities for anti-Ia monoclonal antibodies using L cell transfectants.

The chain specificities of 18 Ak and 26 Ab-reactive anti-Ia monoclonal antibodies have been determined. L cells were transfected with haplotype-matched (A alpha k:A beta k, A alpha b:A beta k) or haplotype-mismatched (A alpha k:A beta b, A alpha b:A beta k) cDNA pairs, lines expressing high levels of surface A complex were selected, and antibody reactivity with a panel of reagents was assessed by cytofluorimetric analysis. Most of the antibodies recognized a determinant specified by one chain, either alpha or (more commonly) beta. A few examples of more complex determinants were also observed. A knowledge of the chain specificities of anti-Ia monoclonal antibodies should prove useful for a variety of studies aimed at dissecting Ia structure-function relationships.

Animals↗
PubMed1986

[Elimination kinetics of organochlorine compounds in the 1st week of breast feeding].

The elimination kinetics of organochlorine compounds (DDE, lindane, aldrin, heptachlor epoxide and heptachlor) from day 2 to day 10 of breast feeding was studied in 39 volunteers who had a baby in the Maternity Department in Nancy. If there was any contamination of the mothers' milk with DDT, the levels were below the level of detection. In contrast, contamination with DDE was high (112.6 ng/g fat content) on day 2, although it decreased rapidly, to 38.6 ng/g by day 3. On day 2, contamination with lindane, aldrin, heptachlor epoxide and heptachlor averaged 43.8, 23.5, 25.4 and 7.4 ng/g fat, respectively, and the levels showed a linear decrease on subsequent days in all cases except that of heptachlor, for which no significant negative correlation with time could be demonstrated. A breast-fed infant thus absorbs measurable quantities of pesticides but not in excess of the acceptable daily doses. Levels of contamination of human milk in France are lower than those reported in Canadian and Italian studies but are higher than the levels in formulated milk.

Aldrin↗
PubMed1986

Stability of metallothionein in gastric juice.

Metallothionein (MT), is presumably the major Cd-binding component of human food. It is not or only partially destroyed by cooking. To study whether MT is stable in gastric juice MT was incubated at various pH values with pepsin and human gastric juice in vitro. Above pH 3.5 nearly all Cd remained bound to the protein and Cd-MT was resistant towards proteolysis. At pH values of 2.5 and 1.7 the protein was digested to 80% and 100%, respectively. At pH 2.5 two Cd-containing peptides with 25-30 amino acids similar to the alpha-domain of the protein were detected. At pH 1.7 these fragments were further degraded to smaller peptides. The results indicate that the pH-dependent proteolytic degradation of Cd-MT depends on the metal content of the protein. Furthermore, the identical results obtained with pepsin and human gastric juice suggest that Cd-MT proteolysis occurs in vivo and will affect Cd resorption.

Amino Acids↗
PubMed1985

An example of interaction between environmental pollutants: modification of thiram toxicity to freshwater organisms by nitrites or nitrates in relation to nitrosamine synthesis.

Thiram, a dithiocarbamate fungicide, is known to evolve to dimethylnitrosamine (DMNA) when associated with nitrites. Conditions of appearance of that carcinogenic compound have been studied in short-term experiments by association of the fungicide, nitrates or nitrites, and species representative of freshwater biota. DMNA has been estimated by GLC equipped with a specific detector. Chlorella vulgaris can rapidly produce nitrites from nitrates and DMNA is obtained in presence of thiram. Daphnia magna can also synthesize DMNA but nitrites have to be added to the medium. Increased toxicity of thiram is observed. The same results are obtained on Cyprinus carpio and for a part on Brachydanio rerio. When the species are associated in a 15-day experimental food chain, and intoxicated algae feed the two other levels, no significant transfer is observed. Nevertheless, some DMNA hazard may exist for particular species exposed to thiram associated with nitrites or even nitrates if algae are present.

Animals↗
PubMed1985

Excretion of nitrates and nitrites in saliva and bile in the dog.

The kinetics of salivary and biliary excretion of inorganic nitrates and nitrites was studied in mongrel dogs after iv injection of these compounds labelled with 15N. There was strong salivary excretion of 15NO-3 after injection of Na15NO3 but little or no nitrites were excreted in the saliva, indicating that the nitrites present in the mouth are mainly the result of in situ transformation of nitrates into nitrites. In the bile, large quantities of nitrates were excreted when the dogs received 15NO-2, indicating endogenous oxidation of the nitrite.

Animals↗
PubMed1984

Des-, syn- and anti-oxyimino-delta 3-cephalosporins. Intrinsic reactivity and reaction with RTEM-2 serine beta-lactamase and D-alanyl-D-alanine-cleaving serine and Zn2+-containing peptidases.

The presence and configuration (syn or anti) of an oxyimino group in the 7 (beta)-acyl side chain of 3-cephems do not modify the intrinsic reactivity of the beta-lactam ring, but have highly enzyme-specific effects. When compared with the corresponding desoxyimino beta-lactam compound: (i) with the plasmid-mediated Escherichia coli RTEM-2 serine beta-lactamase, the substrate activity of the anti isomer is increased and that of the syn isomer is decreased; (ii) with the Streptomyces R61 serine D-alanyl-D-alanine cleaving peptidase (a highly penicillin-sensitive enzyme), the rate of enzyme acylation is not or only little affected when the oxyimino group is in the syn configuration, but is decreased when the oxyimino group is in the anti configuration; (iii) with the Actinomadura R39 serine D-alanyl-D-alanine-cleaving peptidase (an exceedingly highly penicillin-sensitive enzyme), the rate of enzyme acylation is unaffected whatever the configuration of the substituent. The oxidation of the sulphur atom of the dihydrothiazine ring on the beta-face of the molecule makes it both a poorer inactivator of the DD-peptidases and a poorer substrate of the beta-lactamase. The Streptomyces albus G Zn2+-containing D-alanyl-D-alanine-cleaving peptidase (a highly penicillin-resistant enzyme) remains highly resistant to all compounds tested.

Carboxypeptidases↗