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Biomedical subjects

D Klein

Publications and source records attributed to D Klein.

At least 163 records · Page 9Linked to original sources
PubMed1988

Cytomegalovirus infection in a neonatal intensive care unit. Blood transfusion practices and incidence of infection.

We studied blood transfusion variables and cytomegalovirus (CMV) infection in 385 infants admitted to the Duke University Medical Center, Durham, NC, neonatal intensive care unit over 14 months. Cytomegalovirus antibody titers were measured at birth and monthly thereafter. Urine cultures for CMV were performed regularly. Infants admitted in the first six months (n = 197) received conventionally prepared blood. Infants admitted in the remaining eight months (n = 188) were given frozen, deglycerolized blood. Of the 105 infants weighing 1250 g or less (low birth weight [LBW]), 90 (86%) received transfusions. Two hundred eighty infants weighed more than 1250 g (non-LBW), and 111 (40%) of these were given blood. In the first six months of the study, three infants had CMV viruria. One case was congenital; two were acquired. Both infants who acquired infection were antibody-positive at birth and received multiple transfusions. In the remaining eight months, five infants had CMV viruria. Two cases were congenital; three were acquired. The three infants who acquired infection were antibody-positive at birth and received multiple transfusions. Our study demonstrates that infants with an LBW are more likely to receive blood transfusion and to be given significantly more blood than non-LBW infants. There was no difference in the number of infants acquiring CMV in the two periods despite the use of different preparations of blood.

Antibodies, Viral↗
PubMed1988

Nucleotide sequences of chimpanzee MHC class I alleles: evidence for trans-species mode of evolution.

To obtain an insight into the evolutionary origin of the major histocompatibility complex (MHC) class I polymorphism, a cDNA library was prepared from a heterozygous chimpanzee cell line expressing MHC class I molecules crossreacting with allele-specific HLA-A11 antibodies. The library was screened with human class I locus-specific DNA probes, and clones encoding both alleles at the A and B loci have been identified and sequenced. In addition, the sequences of two HLA-A11 subtypes differing by a single nucleotide substitution have been obtained. The comparison of chimpanzee and human sequences revealed a close similarity (up to 98.5%). The chimpanzee A locus alleles showed greatest similarity to the human HLA-A11/A3 family of alleles, one of them being very close to HLA-A11. Similarly, segments of the ChLA-B alleles displayed greatest similarity to certain HLA-B alleles. The calculated evolutionary branch point for the A11-like alleles is 7 x 10(6) to 9 x 10(6) years, whereas the other A locus alleles diverged between 12 x 10(6) and 17 x 10(6) years ago. Since the human and chimpanzee lineages separated 5 x 10(6) to 7 x 10(6) years ago, our data support the notion that during evolution, MHC alleles are transmitted from one species to the next.

Alleles↗
PubMed1988

Serum and quantitative electroencephalographic pharmacokinetics of loprazolam in the elderly.

This study was undertaken to determine the serum pharmacokinetic parameters of loprazolam, a new benzodiazepine hypnotic, in elderly subjects and to compare these with the kinetics of the drug as determined by quantitative EEG analysis. In addition, a 14-day study was undertaken to determine the steady-state serum levels achieved in this population with repeated drug administration. The study was conducted on 16 male and female subjects between the ages of 62 and 72 years, randomly assigned to two groups treated with 0.5 or 1.0 mg of loprazolam. The serum half-life of loprazolam was found to be 5 hours, and the peak serum concentration was reached after 2 hours. Quantitative EEG changes were observed after 30 minutes suggesting rapid access of the drug into the nervous system. Quantitative EEG changes were evident for 9.5 hours, suggesting the persistent effects of an active metabolite. The 14-day study indicated that loprazolam did not accumulate with continued use.

Aged↗
PubMed1988

Both GA2, GM2, and GD2 synthases and GM1b, GD1a, and GT1b synthases are single enzymes in Golgi vesicles from rat liver.

Competition experiments using lactosylceramide, ganglioside GM3 and ganglioside GD3 as substrates, as well as mutual inhibitors for ganglioside N-acetylgalactosaminyltransferase, in Golgi vesicles derived from rat liver suggested that N-acetylgalactosamine transfer to these three respective compounds, leading to gangliosides GA2, GM2, and GD2, respectively, is catalyzed by one enzyme. Analogous studies with gangliosides GA1, GM1, and GD1b as glycolipid acceptors in sialyltransferase assays indicated GM1b, GD1a, and GT1b synthases to be identical. These results are incorporated into a model for ganglioside biosynthesis and its regulation.

Algorithms↗
PubMed1988

Occult thyroid dysfunction in patients with refractory depression.

Assessment of metabolic rate was useful in evaluating refractory depression in six of 15 women. Five of the six had normal levels of T3 and T4; however, each had an elevated thyrotropin-stimulating hormone level or a low metabolic rate. The depressions responded to medication with thyroid hormone.

Adult↗
PubMed1988

Biosynthesis of gangliosides from asialogangliosides in rat liver Golgi vesicles.

Biosynthesis of glycolipids GA2, GA1, GM1b, and GD1c was studied in Golgi vesicles isolated from rat liver. Sequential addition of N-acetylgalactosamine, galactose and two sialic acid residues to lactosylceramide led to the endproduct GD1c. Activities of the corresponding glycosyltransferases were shown to be present in isolated Golgi vesicles and their respective kinetic data were determined. The products of each reaction were characterized by their mobility on thin-layer chromatography, by enzymic degradation to their respective precursors, and in case of GM1b by FAB mass spectrometry.

Animals↗
PubMed1988

Metallothionein gene expression in mouse tissues by D-penicillamine.

The effect of D-penicillamine on metallothionein mRNA accumulation was examined in mouse tissues by Northern and dot blot analysis. This drug was given as a single intraperitoneal dose of 250 mg/kg body weight and the metallothionein mRNA content of the tissues was measured 1, 4, 8 and 24 hours later. A detectable increase of mRNA was observed after 1 hour and maximal accumulation was seen after 4 hours in the liver, kidneys, lungs, brain and spleen, whereas in the heart the maximum occurred after 8 hours. In the liver metallothionein mRNA was increased 14.5-fold over the control and in the kidneys it was increased by a factor of 9.2. A significant increase was also seen in the lungs, where it was 10 fold. To determine whether the increase is due to new transcription of the metallothionein gene, animals were pretreated with actinomycin D (1.0 mg/kg body weight) before receiving D-penicillamine. Actinomycin D prevented some of the D-penicillamine-induced increase in metallothionein mRNA, indicating that the drug, to some extent, acts at the transcriptional level. Regulation of metallothionein gene expression may play an important role in the molecular mechanisms involved in the clinical action of D-penicillamine in rheumatoid arthritis.

Animals↗
PubMed1987

Substrate specificity of GM2 and GD3 synthase of Golgi vesicles derived from rat liver.

Several GM3 derivatives have been synthesized. Among them were lyso-GM3 derivatives and GM3 analogues with modifications in the sialic acid moiety. They were used as glycolipid acceptors in assays for GM2 and GD3 synthase of rat liver Golgi. Analysis of the resulting enzyme activities and of the reaction products revealed different substrate specificities for GM2 and GD3 synthase although the normal glycolipid acceptor for both transferases is ganglioside GM3. Specificity of GD3 synthase is strongly determined by the substrate's negative charge and the acyl residue in amide bond to the amino group of neuraminic acid, while GM2 synthase reacts quite indifferently to these changes in the sialic moiety of the substrate. Both enzymes seem to be sensitive to the spatial extension at the neuraminic acid's carboxylic group.

Animals↗
PubMed1987

The active sites of the beta-lactamases of Streptomyces cacaoi and Streptomyces albus G.

The active-site serine of the extracellular beta-lactamases of Streptomyces cacaoi and Streptomyces albus G has been labelled with beta-iodopenicillanate. The determination of the sequence of the labelled peptides obtained after trypsin digestion of the denatured proteins indicate both enzymes to be class A beta-lactamases. Surprisingly the two Streptomyces enzymes do not appear to be especially homologous, and none of them exhibited a high degree of homology with the Streptomyces R61 DD-peptidase. Our data confirm that, as a family of homologous enzymes, class A is rather heterogeneous, with only a small number of conserved residues in all members of the class.

Amino Acid Sequence↗
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↗