Biomedical subjects

J German

Publications and source records attributed to J German.

At least 19 recordsLinked to original sources

PubMed2005

Modelling of different measures for improving removal in a stormwater pond.

The effect of retrofitting an existing pond on removal efficiency and hydraulic performance was modelled using the commercial software Mike21 and compartmental modelling. The Mike21 model had previously been calibrated on the studied pond. Installation of baffles, the addition of culverts under a causeway and removal of an existing island were all studied as possible improvement measures in the pond. The subsequent effect on hydraulic performance and removal of suspended solids was then evaluated. Copper, cadmium, BOD, nitrogen and phosphorus removal were also investigated for that specific improvement measure showing the best results. Outcomes of this study reveal that all measures increase the removal efficiency of suspended solids. The hydraulic efficiency is improved for all cases, except for the case where the island is removed. Compartmental modelling was also used to evaluate hydraulic performance and facilitated a better understanding of the way each of the different measures affected the flow pattern and performance. It was concluded that the installation of baffles is the best of the studied measures resulting in a reduction in the annual load on the receiving lake by approximately 8,000 kg of suspended solids (25% reduction of the annual load), 2 kg of copper (10% reduction of the annual load) and 600 kg of BOD (10% reduction of the annual load).

Models, Theoretical↗

PubMed2003

Why the lupus problem remains unsolved and I am a human geneticist.

A personal account is given: 1) of my early work with lupus erythematosus including the first observation of formation of the LE cell and the experimental production in animal renal glomeruli of hematoxyphil bodies, the pathognomonic lesion of lupus; and, 2) of how discontinuation of work on lupus--by decree--diverted my life in science away from immunology into another area of human genetics, namely cytogenetics, the discovery of genetically determined genomic instability and the choice of Bloom's syndrome as an investigational model for human cancer.

Animals↗

PubMed2003

Modelling of temperature effects on removal efficiency and dissolved oxygen concentrations in stormwater ponds.

The performance of stormwater ponds, operated under winter conditions, was modelled using the commercial software Mike21 and MOUSE. Direct and indirect effects of changing temperature were investigated. The most important effect of winter conditions is the changed hydrology, characterised by long periods with no runoff followed by snowmelt events with large runoff volumes during several days. This gives lower removal efficiencies than during a period with the same precipitation but without winter conditions. For the concentration of dissolved oxygen, wind is an important factor. Consequently the most important effect of an ice cover on the pond is that it prevents the oxygenation effects of the wind. The direct temperature effects on the removal processes are negligible compared to the indirect effects in changed hydrology and forming of ice cover.

Climate↗

PubMed2002

Metal content and particle size distribution of street sediments and street sweeping waste.

During recent years the interest in street sweeping as a pollutant control measure has increased. For planning of street sweeping programs and disposal of street sweeping waste there is a need to investigate the composition of street sweeping waste and the effect of street sweeping on the remaining sediments on the street. Particle size distribution and heavy metal concentration has been measured for street sweeping waste, street sediments before sweeping and remaining sediments after sweeping. The results show that the concentrations of heavy metals are a function of particle diameter and proportional to the inverse of the particle diameter, i.e. the highest concentrations are found in finest fractions. Regression equations for metal concentrations as a function of particle diameter are presented. According to Swedish guidelines for environmental quality of contaminated sites, heavy metal concentration in the sweeping waste can not be considered as a serious problem. The largest amount of metals and sediment is found in the sandy fractions (0.125-0.5 mm). The street sweeper is more effective in removing coarse sediments than fine. This means that the street sediments after sweeping are finer than the sediments before.

Cities↗

PubMed2001

Back mutation can produce phenotype reversion in Bloom syndrome somatic cells.

A unique and constant feature of Bloom syndrome (BS) cells is an excessive rate of sister-chromatid exchange (SCE). However, in approximately 20% of persons with typical BS, mosaicism is observed in which a proportion of lymphocytes (usually a small one) exhibits a low-SCE rate. Persons with such mosaicism predominantly are genetic compounds for mutation at BLM, and the low-SCE lymphocytes are the progeny of a precursor cell in which intragenic recombination between the two sites of BLM mutation had generated a normal allele. Very exceptionally, however, persons with BS who exhibit mosaicism are homozygous for the causative mutation. In two such exceptional homozygous persons studied here, back mutation has been demonstrated: one person constitutionally was homozygous for the mutation 1544insA and the other for the mutation 2702G-->A. Revertant (low-SCE) lymphoblastoid cells in each person were heterozygous for their mutations, i.e., a normal allele was now present. The normal alleles must have arisen by back mutation in a precursor cell, in one person by the deletion of an A base and, in the other, the nucleotide substitution of a G base for an A base. Thus, back mutation now becomes, together with intragenic recombination, an important genetic mechanism to consider when explaining examples of a reversion of somatic cells to "normal" in persons with a genetically determined abnormal phenotype.

Bloom Syndrome↗

PubMed2001

Primary biodegradability of mineral base oils in relation to their chemical and physical characteristics.

The primary biodegradability of 32 mineral base (i.e., unformulated) oils of paraffinic nature was evaluated using the CEC L-33-A-93 test. These oils were refinery products obtained by varying manufacturing processes. Biodegradation percentages ranged between 15% and 75%, i.e., below the commonly accepted standards for environmentally-compatible lubricants. Biodegradability values were compared to the overall chemical composition and main physical properties of base oils. Biodegradability decreased with increasing levels of aromatic and/or polar compounds in the tested oils. For most oils, the biodegradation percentage increased with the viscosity index, but was a decreasing function of the kinematic viscosity (KV), the pour point, the flash point (FP) and the refractive index (RI). Linear relationships between biodegradability and FP or RI values were observed. These results show that, beside chemical features such as the contents in polar and aromatic compounds, simple physical magnitudes such as KV and RI, commonly used to characterize lubricant properties, may be useful parameters for predicting the biodegradability of mineral base oils.

Biodegradation, Environmental↗

PubMed2000

Viscosity properties of mineral paraffinic base oils as a key factor in their primary biodegradability.

The primary biodegradability of two types of paraffinic base oils (solvent and catalytically dewaxed oils) and their blends was evaluated using the CEC L-33-A-93 test. The biodegradability values varied between 10% and 75%. Base oil mixtures displayed varying contents in aromatic and polar compounds and a wide range of kinematic viscosity (KV) values, from roughly 10 to 600 cSt (at 40 degrees C), while their viscosity indices were almost constant (90-100). The biodegradability of oils was closely related to their content in polycyclic aromatic hydrocarbons and was also decreasing with kinematic viscosity. For the two types of base oils, a linear relationship could be set between the biodegradation percentages and the logarithms of KV values. These results show that, beside overall chemical features such as the contents in aromatic compounds, KV may be a prominent parameter for assessing the primary biodegradability of mineral base oils.

Biodegradation, Environmental↗

PubMed2000

BLM, the Bloom's syndrome protein, varies during the cell cycle in its amount, distribution, and co-localization with other nuclear proteins.

BLM, the protein encoded by the gene mutated in Bloom's syndrome (BS), is a phylogenetically highly conserved DNA helicase that varies in amount and distribution in the nucleus during the cell-division cycle. It is undetectable in many cells as they emerge from mitosis but becomes abundant during G(1) and remains so throughout S, G(2), and mitosis. BLM is widely distributed throughout the nucleus but at certain times also becomes concentrated in foci that vary in number and size. It co-localizes transitorily with replication protein A (RPA) and promyelocytic leukemia protein (PML) nuclear bodies, and at times it enters the nucleolus. The observations support the hypothesis that BLM is distributed variously about the nucleus to manipulate DNA in some, very possibly several, nucleic acid transactions, when and where they take place. The specific transaction(s) remain to be identified. Although absence from the nucleus of functional BLM - the situation in BS - obviously is not lethal in the human, other helicases would appear to be unable to substitute for it completely, witness the hypermutability and hyperrecombinability of BS cells.

Adenosine Triphosphatases↗

PubMed1999

Bloom's syndrome protein, BLM, colocalizes with replication protein A in meiotic prophase nuclei of mammalian spermatocytes.

Bloom's syndrome (BS) is a rare autosomal recessive disorder of humans characterized by severe pre- and postnatal growth deficiency, immunodeficiency, genomic instability, and a predisposition to a wide variety of neoplasms. The genomic instability is evidenced in BS somatic cells as a high incidence of gaps and breaks, chromatid exchanges, chromosome rearrangements, and locus-specific mutations. BS arises from a mutation in BLM, a gene encoding a protein with homology to the RecQ helicase family. Men with BS are sterile; women have reduced fertility and a shortened reproductive span. The current immunocytological study on mouse spermatocytes shows that the BLM protein is first evident as discrete foci along the synaptonemal complexes (SCs) of homologously synapsed autosomal bivalents in late zygonema of meiotic prophase. BLM foci progressively dissociate from the synapsed autosomal axes during early pachynema and are no longer seen in mid-pachynema. BLM colocalizes with the single-stranded DNA binding replication protein A, which has been shown to be involved in meiotic synapsis. However, there is a temporal delay in the appearance of BLM protein along the SCs relative to replication protein A, suggesting that BLM is required for a late step in processing of a subset of genomic DNA involved in establishment of interhomologue interactions in early meiotic prophase. In late pachynema and into diplonema, BLM is more dispersed in the nucleoplasm, especially over the chromatin most intimately associated with the SCs, suggesting a possible involvement of BLM in resolution of interlocks in preparation for homologous chromosome disjunction during anaphase I.

Adenosine Triphosphatases↗

PubMed1999

Transfection of BLM into cultured bloom syndrome cells reduces the sister-chromatid exchange rate toward normal.

The gene BLM, mutated in Bloom syndrome (BS), encodes the nuclear protein BLM, which when absent, as it is from most BS cells, results in genomic instability. A manifestation of this instability is an excessive rate of sister-chromatid exchange (SCE). Here we describe the effects on this abnormal cellular phenotype of stable transfection of normal BLM cDNAs into two types of BS cells, SV40-transformed fibroblasts and Epstein-Barr virus (EBV)-transformed lymphoblastoid cells. Clones of BLM-transfected fibroblasts produced normal amounts of BLM by western blot analysis and displayed a normal nuclear localization of the protein by immunofluorescence microscopy. They had a mean of 24 SCEs/46 chromosomes, in contrast to the mean of 69 SCEs in controls transfected only with the vector. BLM-transfected fibroblast clones that expressed highest levels of the BLM protein had lowest levels of SCE. The lymphoblastoid cells transfected with BLM had SCE frequencies of 22 and 42 in two separate experiments in which two different selectable markers were used, in contrast to 57 and 58 in vector-transfected cells; in this type cell, however, the BLM protein was below the level detectable by western blot analysis. These experiments prove that BLM cDNA encodes a functional protein capable of restoring to or toward normal the uniquely characteristic high-SCE phenotype of BS cells.

Adenosine Triphosphatases↗

PubMed1999

Ulcerative colitis complicated by dysplasia-adenoma-carcinoma in a man with Bloom's syndrome.

Bloom's syndrome (BS) is a rare genetic disorder in which the major clinical feature is growth deficiency. The genome in BS somatic cells is unstable, and hypermutability explains many clinical features. Most notably, affected persons are at enormously increased risk of developing many types of cancers at different sites. It has been well known that ulcerative colitis (UC) is associated with the spectrum of epithelial changes signifying dysplasia and the progression to frank carcinoma. We report here a case of UC complicated by dysplasia-adenoma-carcinoma sequence in a 37-year-old man with BS.

Adenocarcinoma↗

PubMed1999

Sclerosing hyaline necrosis of the liver in Bloom syndrome.

Bloom syndrome is a rare autosomal recessive disorder characterized by normally proportioned but strikingly small body size, a characteristic facies and photosensitive facial skin lesion, immunodeficiency, and a marked predisposition to development of a variety of cancers. We describe here, we believe for the first time, pronounced sclerosing hyaline necrosis with Mallory bodies in the liver of a patient with Bloom syndrome. Mallory bodies are cytoplasmic eosinophilic inclusions, which are more common in visibly damaged, swollen hepatocytes in various liver diseases but are never found in normal liver. The possible pathogenesis of this finding in Bloom syndrome is discussed.

Adult↗

PubMed1998

A rapid method for detecting the predominant Ashkenazi Jewish mutation in the Bloom's syndrome gene.

Bloom's syndrome (BS) is a rare, autosomal recessive disease characterized by sun sensitivity, short stature, and predisposition to cancer. Although rare in the general population, BS is more common in the Ashkenazi Jewish population (German, 1993). The isolation of the gene for BS, known as BLM, has permitted the identification of mutations within the gene and the discovery that most BS individuals of Ashkenazi Jewish origin carry the identical 6-bp deletioin/7-bp insertion at position 2,281 of BLM (blmAsh). We have developed a rapid method for detecting blmAsh based on restriction enzyme digestion of a PCR product containing the mutation. blmAsh creates a restriction site within the amplified fragment allowing distinction of normal and mutant DNAs. This method has been designed for use with genomic DNA or cDNA.

Adenosine Triphosphatases↗

PubMed1998

Carrier frequency of the Bloom syndrome blmAsh mutation in the Ashkenazi Jewish population.

Bloom syndrome is more common in individuals of Ashkenazi Jewish descent than in any other population, and one particular mutation in the Bloom syndrome gene, blmAsh, is homozygous in nearly all Ashkenazi Jewish persons with Bloom syndrome. We have determined the frequency of blmAsh in 1491 Ashkenazi Jewish persons with no known history of Bloom syndrome and found that 1 in 107 persons was heterozygous. Although not common, genetic screening for Bloom syndrome is feasible in this population.

Adenosine Triphosphatases↗

PubMed1998

Somatic hypermutation of immunoglobulin genes is independent of the Bloom's syndrome DNA helicase.

Immunoglobulin gene somatic mutation leads to antibody affinity maturation through the introduction of multiple point mutations in the antigen binding site. No genes have as yet been identified that participate in this process. Bloom's syndrome (BS) is a chromosomal breakage disorder with a mutator phenotype. Most affected individuals exhibit an immunodeficiency of undetermined aetiology. The gene for this disorder, BLM, has recently been identified as a DNA helicase. If this gene were to play a role in immunoglobulin mutation, then people with BS may lack normally mutated antibodies. Since germ-line, non-mutated immunoglobulin genes generally produce low affinity antibodies, impaired helicase activity might be manifested as the immunodeficiency found in BS. Therefore, we asked whether BLM is specifically involved in immunoglobulin hypermutation. Sequences of immunoglobulin variable (V) regions were analysed from small unsorted blood samples obtained from BS individuals and compared with germ-line sequences. BS V regions displayed the normal distribution of mutations, indicating that the defect in BS is not related to the mechanism of somatic mutation. These data strongly argue against BLM being involved in this process. The genetic approach to identifying the genes involved in immunoglobulin mutation will require further studies of DNA repair- and immunodeficient individuals.

Adult↗

PubMed1998

The Ashkenazic Jewish Bloom syndrome mutation blmAsh is present in non-Jewish Americans of Spanish ancestry.

Bloom syndrome (BS) is more frequent in the Ashkenazic Jewish population than in any other. There the predominant mutation, referred to as "blmAsh," is a 6-bp deletion and 7-bp insertion at nucleotide position 2281 in the BLM cDNA. Using a convenient PCR assay, we have identified blmAsh on 58 of 60 chromosomes transmitted by Ashkenazic parents to persons with BS. In contrast, in 91 unrelated non-Ashkenazic persons with BS whom we examined, blmAsh was identified only in 5, these coming from Spanish-speaking Christian families from the southwestern United States, Mexico, or El Salvador. These data, along with haplotype analyses, show that blmAsh was independently established through a founder effect in Ashkenazic Jews and in immigrants to formerly Spanish colonies. This striking observation underscores the complexity of Jewish history and demonstrates the importance of migration and genetic drift in the formation of human populations.

Adenosine Triphosphatases↗

PubMed1997

Bloom's syndrome. XX. The first 100 cancers.

As of 1996 the 100th cancer was diagnosed in Bloom's syndrome. The cancers have been regularly documented since 1960 in a program of surveillance referred to as the Bloom's Syndrome Registry. Tabulated here are their types and ages of onset. The 100 cancers arose in 71 of the 168 registered individuals. Represented in Bloom's syndrome are both the cancers that commonly affect the general population and the rare tumors of early childhood. This body of information has become sufficiently large to be useful to geneticists and physicians in advising affected families concerning cancer risk. Of more general significance, however, the distribution of cancer sites and types sets Bloom's syndrome apart from other cancer-predisposing genetically determined conditions, affirming its experimental value as a model for analyzing the nonenvironmental component in the etiology of the generality of human cancer.

Adolescent↗

PubMed1996

Physical mapping of the bloom syndrome region by the identification of YAC and P1 clones from human chromosome 15 band q26.1.

The gene for Bloom syndrome (BLM) has been mapped to human chromosome 15 band q26.1 by homozygosity mapping. Further refinement of the location of BLM has relied upon linkage-disequilibrium mapping and somatic intragenic recombination. In combination with these mapping approaches and to identify novel DNA markers and probes for the BLM candidate region, a contiguous representation of the 2-Mb region that contains the BLM gene was generated and is presented here. YAC and P1 clones from the region have been identified and ordered by using previously available genetic markers in the region along with newly developed sequence-tagged sites from radiation-reduced hybrids, polymorphic dinucleotide repeat loci, and end sequences of YACs and P1s. A long-range restriction map of the 2-Mb region that allowed estimation of the distance between polymorphic microsatellite loci is also reported. This map and the DNA markers derived from it were instrumental in the recent identification of the BLM gene.

Adenosine Triphosphatases↗