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Biomedical subjects

D Klein

Publications and source records attributed to D Klein.

At least 145 records · Page 8Linked to original sources
PubMed1992

Pieces of the puzzle: steps toward affordable health care.

This essay proposes a multiple-part solution to the health care affordability crisis. Solution elements include: changing the most commonly held health insurance product to a plan with high-deductible design, and reinstituting community-based health planning. It is proposed that the federal tax code be used to create incentives to change the most commonly held benefit. Further, it is suggested that "capital licenses" be provided to support health planning.

Capital Expenditures↗
PubMed1992

[Treatment of Fournier's gangrene. A review based on 3 new cases].

We describe three new cases of Fournier's gangrene-a necrotizing fasciitis of urogenital or anorectal origin. Though in the initial report the disease was believed to be idiopathic, the source of infection or immuncompromising factors can be identified in nearly all cases today. We present a combination of aggressive surgical therapy and adjunctive use of Imipenem which was successful in the treatment of all our cases. By using fully resorbable nutrition colostomy could be avoided successfully.

Adult↗
PubMed1992

Molecular genetic study of human arginase deficiency.

We have explored the molecular pathology in 28 individuals homozygous or heterozygous for liver arginase deficiency (hyperargininemia) by a combination of Southern analysis, western blotting, DNA sequencing, and PCR. This cohort represents the majority of arginase-deficient individuals worldwide. Only 2 of 15 homozygous patients on whom red blood cells were available had antigenically cross-reacting material as ascertained by western blot analysis using anti-liver arginase antibody. Southern blots of patient genomic DNAs, cut with a variety of restriction enzymes and probed with a near-full-length (1,450-bp) human liver arginase cDNA clone, detected no gross gene deletions. Loss of a TaqI cleavage site was identified in three individuals: in a homozygous state in a Saudi Arabian patient at one site, at a different site in homozygosity in a German patient, and in heterozygosity in a patient from Australia. The changes in the latter two were localized to exon 8, through amplification of this region by PCR and electrophoretic analysis of the amplified fragment after treatment with TaqI; the precise base changes (Arg291X and Thr290Ser) were confirmed by sequencing. It is interesting that the latter nucleotide variant (Thr290Ser) was found to lie adjacent to the TaqI site rather than within it, though whether such a conservative amino acid substitution represents a true pathologic mutation remains to be determined. We conclude that arginase deficiency, though rare, is a heterogeneous disorder at the genotypic level, generally encompassing a variety of point mutations rather than substantial structural gene deletions.

Amino Acid Sequence↗
PubMed1991

The mutation Lys234His yields a class A beta-lactamase with a novel pH-dependence.

The lysine-234 residue is highly conserved in beta-lactamases and in nearly all active-site-serine penicillin-recognizing enzymes. Its replacement by a histidine residue in the Streptomyces albus G class A beta-lactamase yielded an enzyme the pH-dependence of which was characterized by the appearance of a novel pK, which could be attributed to the newly introduced residue. At low pH, the kcat, value for benzylpenicillin was as high as 50% of that of the wild-type enzyme, demonstrating that an efficient active site was maintained. Both kcat. and kcat/Km dramatically decreased above pH 6 but the decrease in kcat./Km could not be attributed to larger Km values. Thus a positive charge on the side chain of residue 234 appears to be more essential for transition-state stabilization than for initial recognition of the substrate ground state.

Ampicillin↗
PubMed1991

Effect of an adjacent base on detection of a point mutation by restriction enzyme digestion.

While routinely mapping point mutations within the arginase locus of a collection of hyperargininemic patients, we discovered that a base immediately outside a restriction endonuclease recognition site (TaqI) can eliminate cleavage of this site by this enzyme. The genetic lesion lay in a base immediately flanking a TaqI recognition site within exon 8 of the arginase locus and abolished cutting by approximately 80%. We wish to emphasize the necessity of heeding subtle cues frequently encountered while generating restriction enzyme data, because neither Southern blot maps nor endonuclease digestion of polymerase chain reaction amplified products of exon 8 accurately predicted where the point mutation lay. To our knowledge, this is the first instance of inhibition of cleavage by flanking bases occurring on natural (nonsynthetic) DNA substrates, i.e., within the clinical setting of characterization of a human genetic disorder.

Base Sequence↗
PubMed1991

Gorilla major histocompatibility complex-DRB pseudogene orthologous to HLA-DRBVIII.

The HLA-DR4 haplotype consists of four DRB genes: DRB1*04, DRBVII, DRBVIII, and DRB4*01, arranged in this order on the chromosome. The DRB1 and DRB4 genes code for beta chains of the alpha beta heterodimers expressed on the cell surface and bearing the HLA-DR4 and HLA-DRw53 determinants, respectively; the DRBVII and DRBVIII are pseudogenes. We found and sequenced a gene closely related to HLA-DRBVIII in the genome of the lowland gorilla "Sylvia." We designate this gene Gogo-DRB8. The close relationship between the two genes is indicated by the overall sequence similarity, the absence of recognizable exons 1 and 2 in both genes, the presence of two Alu repeats at corresponding positions, and high sequence similarity between corresponding repeats. The comparison with an outgroup (tamarin) gene and the functional counterparts of the DRB8 gene indicate that DRB8 emerged between 18 and 26 million years ago and became inactivated at the same time as or shortly after its creation. Hence DRB8 has probably existed as a pseudogene since the divergence of apes from Old World monkeys more than 20 million years ago.

Animals↗
PubMed1991

Metallothionein, copper and zinc in fetal and neonatal human liver: changes during development.

Total and cytosolic zinc (Zn) and copper (Cu), cytosolic metallothionein (MT) and the Cu-load of MT were investigated in fetal (22, 24 and 32 gestational weeks) and neonatal (2-15 months) human liver. Whereas the fraction of cytosolic Zn remained constant at 66% of the total independent of the stage of development, the fraction of cytosolic Cu increased from 26% in preterm liver to about 100% within 12 months postnatally. The MT content was higher in fetal than in neonatal liver. There was a linear correlation (r = 0.996) between cytosolic MT and Zn in both fetal and neonatal liver but not between MT and Cu. In contrast to fetal liver, the Cu-load of MT in neonatal liver seems to be determined by the Zn/Cu ratio in the cytosol. The results suggest that MT is involved in the regulation of Cu and Zn metabolism during fetal and neonatal development.

Aging↗
PubMed1990

Quantitation of Cu-containing metallothionein by a Cd-saturation method.

A rapid and sensitive method for determining Cu-containing metallothionein (MT) is described. The main features of this Cd-saturation assay are: high-molecular-weight Cd-binding compounds are denatured with acetonitrile (50% final concentration), Cu bound to MT is removed with ammonium tetrathiomolybdate, excessive tetrathiomolybdate and its Cu complexes are removed with DEAE-Sephacel, apothionein is saturated with Cd, and excessive Cd is bound to Chelex 100. The thiomolybdate assay is capable of reliably detecting 14 ng MT and thus is particularly suitable for measuring MT in small tissue samples (e.g., biopsies), in extrahepatic tissues, and in cultured cells. Moreover, the combination of the thiomolybdate assay with the recently developed Cd-Chelex assay also makes it possible to determine the portion of MT which binds Cu (Cu load of MT), provided that the amount of non-Cu-thionein exceeds 100 ng, the detection limit of the Cd-Chelex assay.

Animals↗
PubMed1990

The Cd-Chelex assay: a new sensitive method to determine metallothionein containing zinc and cadmium.

A rapid and sensitive one-vial procedure to determine metallothionein (MT) containing zinc (Zn) and cadmium (Cd) is described. New features of this Cd-saturation method are: high molecular weight Cd-binding proteins are denatured by treatment with acetonitrile (50% final concentration), and excess of Cd is bound to a cation exchange resin (Chelex-100). With this method, MT has been measured, e.g. in liver of control and zinc- or cadmium-treated rats, in human liver and in cultured human fibroblasts down to absolute amounts of 0.1 microgram. The Cd-Chelex assay is 10 times more sensitive than the established Cd-heme assay (Dieter et al. 1986) and therefore is particularly suitable to quantify MT in small tissue samples (e.g., liver biopsies of a few milligrams) and in extrahepatic tissues or cell cultures with low MT concentrations.

Adolescent↗
PubMed1990

Longitudinal change in HIV transmission risk behaviors by gay male physicians.

Gay male physicians were surveyed in 1984 and 1985 about their knowledge and attitudes regarding HIV transmission and AIDS and changes they had made in social, health-related, and sexual activities since the onset of the AIDS epidemic. Most of the 37 subjects who participated in both surveys progressively lessened their participation in HIV transmission risk behaviors over time. Health belief, AIDS knowledge, health coping, social support, mood state, and age factors all contributed to changes in sexual behavior. The modeling of sexual-behavior changes showed general stability over time. This study provides further evidence that multiple psychosocial factors are associated with changes in sexual behavior, even in gay male physicians.

Adult↗
PubMed1990

[Development of genetic research in ophthalmology with special reference to Switzerland].

The relationship between ophthalmology and genetics has always been a very active one, and existed even before Mendel's laws of inheritance were known. The pedigree method in particular yielded satisfactory results even to the first researchers. Later, Helmholtz's invention of the ophthalmoscope (in 1851) and the rediscovery of Mendel's laws of heredity (in 1900) made major contributions to the progress of human genetics in ophthalmology. Credit is due to J. F. Horner of Zurich (1831-1886) for having first established the X-chromosomal inheritance of colorblindness. Subsequently, the development of genetic research was advanced in particular by Alfred Vogt, Professor of Ophthalmology in Zurich (1879-1943) and Adolf Franceschetti in Geneva (1896-1968) and their co-workers. We are indebted to Vogt for the first description of albinismus solum bulbi. Credit is also due to him for having made early diagnosis of myotonic dystrophy (Steinert) possible, a major discovery for genetic counseling. He was the first to detect, by slit-lamp examination, characteristic lens changes in the form of whitish, red, and green opacities in the anterior and posterior subcapsular regions. Franceschetti's achievements include the description of several clinical syndromes, of which mandibulofacial dysostosis has become well known. Among the hereditary retinal dystrophies, he described fundus flavimaculatus (yellowish lesions disseminated in the deeper layers of the posterior pole) as a new entity, attributed to degeneration of the pigment epithelium. In addition to more than 500 articles, he was also co-author, with J. François and J. Babel, of a monumental handbook in two volumes titled Hérédodégénérescences choriorétiniennes (of which an English translation appeared in 1974).(ABSTRACT TRUNCATED AT 250 WORDS)

Eye Diseases↗
PubMed1990

Evolution of the class II major histocompatibility complex alleles in higher primates.

We have shown that chimpanzees and gorillas have DRB alleles very similar to those of humans. The existence of similar DRB alleles in the different species of higher primates cannot be accounted for by convergent evolution of unrelated alleles that arose independently after the speciation. We therefore conclude that ancestral DRB alleles, that had existed before the speciation, were transmitted to the ancestors of humans, chimpanzees, and gorillas. This conclusion indicates that the diversification of MHC alleles does not start at the inception of a species, but rather proceeds beyond the lifespan of a species. A high degree of sequence similarity found between certain human and non-human primate DRB alleles shows that MHC alleles do not diversify rapidly. The bulk of the contemporary DRB polymorphism seems to have been generated by accumulation of random point mutations during long evolutionary periods preceding the divergence of humans, chimpanzees, and gorillas.

Alleles↗