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Biomedical subjects

H Bertram

Publications and source records attributed to H Bertram.

11 recordsLinked to original sources

Radical effects on mutation spectra in lambda phage.

Mutations in the lambda repressor gene cI (710 bp) were induced by 60Co-gamma radiation in dissolved lambda phage DNA. After in vitro DNA packaging to lambda phage particles (pack phage) and phenotypic expression of the mutants, DNA was sequenced directly. Two-thirds of mutations were located in the amino terminus region of the gene without any signs of hotspots. Changes consisted of (+1) insertions (25%) and base substitutions (75%). Transitions were exclusively G/C to A/T. Transversions were mostly G/C to C/G and few G/C to T/A. We did not find A/T to T/A transversions, A/T to G/C transitions, deletions and gross rearrangements. In most of the base substitutions a pre-existing base pair had been replaced by an A/T pair; this might come from 'non-instructional sites' like abasic sites. Several mechanisms for base substitutions are considered.

Bacteriophage lambda

[Neonatal variant of Bartter syndrome].

A male preterm infant of 32 weeks of gestation with history of severe polyhydramnios during pregnancy presented soon after birth with polyuria with initial sodium chloride loss subsequently followed by increasing potassium loss. After manifestation of hypokalaemia, hypochloraemia, alkalosis and high urinary prostaglandin concentrations, the diagnosis of the neonatal variant of Bartter's syndrome was made. The treatment consisted of administered of large amounts of fluid with sodium chloride and potassium supplementation and indomethacin (1.5 to 2 mg/kg per day).

Bartter Syndrome

Evidence for a preglomerular oxygen diffusion shunt in rat renal cortex.

Although blood flow to the renal cortex is high and oxygen extraction is low, the renal cortex is remarkably susceptible to hypoxia. Because erythropoietin production has been localized mainly to the renal cortex, the aim of this study was to find a common denominator for both the high susceptibility to hypoxia and oxygen sensing within the renal cortex. By direct measurement of oxygen pressure with microcoaxial needle sensors at superficial glomeruli of the in situ kidney of anesthetized Munich-Wistar-Frömter rats, we obtained mean partial pressure of O2 (PO2) values of 46 +/- 13 (SD) mmHg (n = 71). The simultaneously measured systemic PO2 in arterial blood was 90 +/- 8 mmHg (n = 54). Changing the respirator gas from air to pure oxygen enhanced systemic arterial PO2 to 593 +/- 27 mmHg, whereas PO2 at the superficial glomeruli increased only to a mean of 80 +/- 28 mmHg (n = 71). These data suggest significant preglomerular shunting of oxygen within the cortical vasculature, most likely between interlobular vessels, which are arranged in a countercurrent fashion and represent quantitatively the largest contact area between arteries and veins within the renal cortex.

Air

Osteolysis in alloarthroplasty of the hip. The role of bone cement fragmentation.

Movement at the interface between bone and cement and fractures of the cement can cause fragmentation of the polymethylmethacrylate (PMMA) bone cement implant. In order to obtain further information about the effect of PMMA fragments on the surrounding tissue and the role of such particles in the development of bone resorption, the authors investigated 17 patients with cemented total hip endoprostheses showing osteolysis and implant loosening in the femoral shaft with (Group B) and without (Group A) involvement of the acetabulum. The roentgenographic follow-up examinations revealed an initially slow and later more rapid extension of the endosteal bone erosions, with a predilection for the tip of the stem, the lesser trochanter, and laterally for the middle of the stem. At revision surgery, tissue samples were taken from the joint capsule and the bone-cement interface, in particular from the osteolysis in the femoral shaft and the acetabulum. The tissue samples were processed for histology, microscopically examined, and semiquantitatively evaluated. The retrieved devices were also carefully inspected. Large foreign-body granulomas were found at the bone-cement interface and in the joint capsule. Histiocytes and foreign-body giant cells stored particles of PMMA and polyethylene, of which fragmented bone cement predominated. Granulomatous tissue invaded bone canals and marrow spaces and induced resorption of the surrounding bone. In four cases in Group A, tissue from the osteolysis contained only fragmented bone cement, demonstrating that PMMA particles alone may be responsible for triggering focal bone resorption. Osteolysis seems to begin at the site where disintegration of bone cement begins. In cases in which polyethylene particles were found in the tissue in addition to fragmented bone cement, wear from the ultrahigh molecular weight polyethylene socket has been increased by entrapment of PMMA particles between the joint surfaces. Thus, fragmentation of bone cement and abrasion of polyethylene enhance each other. Bone cement particles promote polyethylene wear, which in turn promotes granuloma formation, bone resorption, and subsequent bone cement disintegration.

Acetabulum

Osteolysis in alloarthroplasty of the hip. The role of ultra-high molecular weight polyethylene wear particles.

Massive localized osteolysis around artificial joints has been seen more frequently in the past few years. It is still not generally accepted that ultra-high molecular weight polyethylene (UHMWPE) wear particles can induce massive bone resorption, even distant from the joint. This article describes a series of eight soft-top prostheses with large UHMWPE ball heads that contributed to the erosion of surrounding bone. Roentgenographically, all of the cases showed a marked loss of proximal cortical bone, more or less combined with osteolysis, which was distal to the femoral shaft and deep into the acetabulum. In two cases, remodeling and resorption transformed the bone into a tumorlike appearance. Tissue samples from areas of osteolysis as well as from the joint capsule were taken at revision surgery, processed for histology, examined microscopically, and evaluated semiquantitatively. The retrieved devices were also carefully inspected. Large amounts of UHMWPE wear debris were found not only in the joint capsule but also in layers of granulomatous tissue from the acetabulum and femur, whereas metal particles and fragmented polymethylmethacrylate were either completely absent or occurred only in very small amounts. The results of this study demonstrate that UHMWPE wear products alone can cause massive osteolysis by triggering foreign-body granuloma formation at the bone-cement interface; the bone cement may remain fixed in areas beyond the osteolytic transformation.

Acetabulum

Action of gamma endonuclease on clustered lesions in irradiated DNA.

Irradiation of DNA in situ i.e. in phage particles or in the cell leads to alterations of single DNA nucleotides as well as to clustered lesions such as double strand breaks or unpaired DNA regions the latter being sensitive to digestion by S1 nuclease. A contribution will be made to the configuration of such S1-nuclease-sensitive sites (S1 sites). DNA from irradiated lambda phage containing S1 sites was treated with gamma endonuclease from M. luteus which is known to split the nucleotide strand at the position of oxidized pyrimidine base. It was found that the gamma endonuclease induces double-strand breaks at some of the S1 sites indicating double base damage within this site. However, half of the S1 sites are not converted into a double-strand break by the gamma endonuclease, indicating base damage only on one strand within the unpaired region.

Aspergillus oryzae

DNA damage and mutagenesis of lambda phage induced by gamma-rays.

Lambda phage DNA was gamma-irradiated in aqueous solution and the amount of radiation-induced strand breakage [double- and single-strand breaks and alkali-labile sites (dsb, ssb, als)] was determined. Twice as much minor structural damage (ssb and als) per lethal hit was found in this DNA compared with DNA from irradiated phage suspensions. The in vitro irradiated DNA was re-packaged into infectious particles ('pack-phage'). The induction of mutations in the cI or cII cistron was scored using SOS-induced host cells. The in vitro prepared particles were found to have second-order kinetics for mutagenesis induced by gamma-rays indicating that two pre-mutational events were necessary to produce a mutation. In contrast, bacteria-free phage suspensions ('lys-phage') showed single hit kinetics for mutagenesis after irradiation. The increase in the mutation rate in the phage particles was mainly due to minor lesions, i.e. ssb, als and unidentified base damage. In lys-phage, mutagenesis might be enhanced by clustered DNA damage--a configuration which does not exist in pack-phage. The loss of infectivity was analysed in comparison with the extent of structural damage. All lesions investigated here contributed to biological inactivation. Minor lesions were tolerated by lambda phage to a limited extent. Major lesions, such as dsb, contributed most to the loss of infectivity and can be considered as lethal events.

Bacteriophage lambda

Differences in plasma and tissue aluminum concentrations due to different aluminum-containing drugs in patients with renal insufficiency and with normal renal function.

The gastrointestinal absorption of aluminum from orally administered aluminum-containing drugs is well documented. Retention of the absorbed aluminum leads to elevated levels of this metal in the tissue of patients with renal failure. We studied two groups of dialysis patients who had received equal amounts of the different aluminum-containing phosphate-binders Aludrox and Antiphosphat. It has recently been shown that Antiphosphat releases only a few aluminum ions in an environment of low pH. Consistent with this finding, we found the aluminum levels to be significantly higher in the plasma, bone, and hair of patients who had received Aludrox as phosphate binder. Subjects with normal renal function excreted most of the ingested and absorbed aluminum. No data are available concerning the tissue load of the element in these subjects. We studied two groups of patients with normal renal function who had received antacid drugs prior to neurosurgery on a brain tumor. The first group of patients were treated with an aluminum-rich antacid (Maalox 70); the other group received an aluminum-poor drug (magaldrate) for 10 days prior to the operation. Analysis of the brain-tissue removed revealed twofold higher aluminum levels in the patients who had received Maalox 70. These results indicate that administration of aluminum-containing drugs leads to a tissue load of aluminum in patients with an impaired renal function as well as in those with a normal function. The extent of the aluminum load depends on the aluminum content and the liberation rate of the drug.

Aluminum