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Biomedical subjects

A Hartmann

Publications and source records attributed to A Hartmann.

At least 253 records · Page 14Linked to original sources
PubMed1997

Flow cytometric analysis of herpes simplex virus type 1 susceptibility to acyclovir, ganciclovir, and foscarnet.

We established a quantitative flow cytometric method for determination of herpes simplex virus type 1 (HSV-1) susceptibility to acyclovir (ACV), ganciclovir, and foscarnet in vitro. Susceptibility was defined in terms of the drug concentration which reduced the number of cells expressing HSV-1 glycoprotein C (gpC) with a fluorescence intensity of > or =10(2) by 50% (IC50). Flow cytometry allowed us to use a high (1.0) as well as a low (0.005) multiplicity of infection, and determination of the IC50 was possible after one or more viral replicative cycles. IC50s were dependent on virus input and on time postinfection. In mixture experiments, 1 to 2% resistant viruses added to a sensitive strain could be detected. The results obtained by flow cytometry showed a good qualitative correlation with those achieved by cytopathic effect inhibitory assay. However, flow cytometry might detect more quantitative differences in drug susceptibility, especially among resistant strains, as confirmed also by determination of intracellular drug phosphorylation. The mean IC50s for ACV-sensitive strains were 0.45 to 1.47 microM, and those for ACV-resistant strains were between 140 and 3,134 microM. Flow cytometric analysis was fast and accurate, automatizable, and highly reproducible. Flow cytometry may be a more powerful tool than standard cytopathic effect-based assays and could have advantages for the detection of low levels of drug resistance or mixtures of sensitive and resistant virus strains.

Acyclovir↗
PubMed1997

Root colonization of different plants by plant-growth-promoting Rhizobium leguminosarum bv. trifolii R39 studied with monospecific polyclonal antisera.

Monospecific polyclonal antisera raised against Rhizobium leguminosarum bv. trifolii R39, a bacterium which was isolated originally from red clover nodules, were used to study the colonization of roots of leguminous and nonleguminous plants (Pisum sativum, Lupinus albus, Triticúm aestivum, and Zea mays) after inoculation. Eight weeks after inoculation of soil-grown plants, between 0.1 and 1% of the total bacterial population in the rhizospheres of all inoculated plants were identified as R. leguminosarum bv. trifolii R39. To characterize the associative colonization of the nonleguminous plants by R.leguminosarum bv. trifolii R39 in more detail, a time course study was performed with inoculated roots of Z. mays. R. leguminosarum bv. trifolii R39 was found almost exclusively in the rhizosphere soil and on the rhizoplane 4 weeks after inoculation. Colonization of inner root tissues was detected only occasionally at this time. During the process of attachment of R. leguminosarum bv. trifolii R39 to the rhizoplane, bacterial lipopolysaccharides were overexpressed, and this may be important for plant-microbe interaction. Fourteen weeks after inoculation, microcolonies of R. leguminosarum bv. trifolii R39 were detected in lysed cells of the root cortex as well as in intracellular space of central root cylinder cells. At the beginning of flowering (18 weeks after inoculation), the number of R. leguminosarum bv. trifolii R39 organisms decreased in the rhizosphere soil, rhizoplane, and inner root tissue.

Antigens, Bacterial↗
PubMed1997

Confirmation of CT criteria to distinguish pathophysiologic subtypes of cerebral infarction.

PURPOSE: To determine whether cerebral infarctions classified as embolic or hemodynamic by their appearance on CT scans reflect distinct pathophysiologic entities. METHODS: Cerebral infarctions were retrospectively classified into two groups according to their morphologic appearance on CT scans: territorial infarctions and watershed, or terminal supply area, infarctions. Specific CO2 reactivity for both groups of patients was determined with the xenon-133 method and 32 stationary detectors. Twenty-one patients with unilateral, supratentorial, ischemic cerebral infarctions were selected. CT findings were highly suggestive of a territorial infarction in 14 patients (mean age, 56 years) and of a watershed infarction in seven patients (mean age, 52 years). RESULTS: The initial slope index of the territorial and watershed infarction groups during CO2 inhalation was 55.1 +/- 2.4 sec-1 and 52.0 +/- 1.9 sec-1, respectively, in the infarcted hemispheres and 58.3 +/- 2.3 sec-1 and 55.1 +/- 1.5 sec-1, respectively, in the noninfarcted hemispheres. CO2 reactivity of the unaffected detectors was 1.75 +/- 0.3 sec-1 mm Hg-1 and 1.51 +/- 0.2 sec-1 mm Hg-1 for the territorial and watershed infarction groups, respectively. CO2 reactivity of the affected detectors was 1.75 +/- 0.3 sec-1 mm Hg-1 and 1.27 +/- 0.2 sec-1 mm Hg-1 for the two groups, respectively. The CO2 reactivity difference between affected detectors of the hemodynamic group and age-matched healthy control subjects was significant. CONCLUSIONS: The difference in CO2 reactivity between the two groups supports the concept that CT criteria can identify two pathophysiologic entities. In addition, we conclude that during the chronic stage, lower CO2 reactivity of the watershed infarction indicates that the global hemodynamic situation in these infarcts is more severely compromised than in territorial infarctions.

Aged↗
PubMed1997

[Contents of a "basic psychosomatic management" curriculum. Results of a 4-year concomitant evaluation].

The results of evaluations proceeding the educational seminar "Psychosomatic Primary Care" in South Baden are presented and analyzed. From 1991 to 1995, approximately 450 physicians took part in these courses. From critical feedback and suggestions for improvement obtained from participants following each course, recommendations for future seminars pertaining to content, structure, process, didactic and evaluation are presented.

Adult↗
PubMed1997

Direct examination of subgingival plaque from a diseased periodontal site using confocal laser scanning microscopy (CLSM).

Material taken directly from a periodontal site was investigated using immunofluorescence, acridine orange staining and confocal laser scanning microscopy (CLSM). Porphyromonas gingivalis was tracked by a specific polyclonal antibody and its pronounced occurrence in inflamed as compared to non-inflamed areas was demonstrated. Further accompanying microorganisms were counterstained with acridine orange which could provide information on the viability of individual cells. Optical sections by laser microscopy revealed the spatial arrangement of the investigated material. The combination of specific staining and CLSM allows a detailed microbiological investigation of clinical material obtained directly without cultivation.

Antibodies, Bacterial↗
PubMed1996

The C-terminal domain of light-harvesting chlorophyll-a/b-binding protein is involved in the stabilisation of trimeric light-harvesting complex.

Light-harvesting chlorophyll a/b-binding protein (LHCP) can be reconstituted with pigments in detergent solution to yield stable monomeric light-harvesting chlorophyll a/b complex (LHCII). This reconstitution is not significantly affected when up to ten amino acids are deleted on the C-terminus of LHCP or when a tryptophan, which is 11 positions from the C terminus (W222), is exchanged with other amino acids [Paulsen, H. & Kuttkat, A. (1993) Photochem. Photobiol. 57, 139-142]. Here we show that the exchange of W222 with histidine or glycine completely abolishes the ability of the protein to assemble into trimeric LHCII, either upon reconstitution of monomeric complexes in detergent solution or upon insertion into isolated thylakoids. It is concluded that part of the hydrophilic domain on the C-terminus of LHCP, although not essential for the formation of stable monomeric LHCII, is involved in trimer formation. The different degree to which various amino acids in place of W222 affect trainer formation suggests that a hydrophobic amino acid is needed in this position.

Amino Acid Sequence↗
PubMed1996

Molecular epidemiology of breast cancers in northern and southern Japan: the frequency, clustering, and patterns of p53 gene mutations differ among these two low-risk populations.

Comparison of acquired mutations in the p53 tumor suppressor gene can illuminate factors contributing to carcinogenesis among cancer cohorts. Japan has an ethnically homogeneous population with a low incidence of breast cancer. Previously we reported an unusual frequency, allelic status, and clustering of mutations in breast cancers from the northern part of the main Japanese island. To extend these findings, exons 2-11 and adjacent intronic sequences were analysed in tumors of women from northern (Hokkaido) and southern (Tokushima) Japan. The frequency of breast cancers with p53 gene mutations in the Hokkaido group is the highest reported (81%) while that in Tokushima (28%) is similar to most other populations. Thirteen of the 19 mutations (68.4%) in the Hokkaido cohort were heterozygous, an unusually high frequency for p53 mutations in any tumor type. There were three missense mutations at codon 175, a known hotspot for alterations in the p53 gene, and three missense mutations at codon 179, a rare site for p53 changes. In addition, the patterns of p53 gene mutation differed between the two Japanese cohorts (P=0.04). The multiple differences in acquired p53 mutations suggest unsuspected biological differences among breast cancers in northern and southern Japan. In addition, the high frequency of p53 mutations in breast cancers from Hokkaido predicted a poorer prognosis for this population which was confirmed on examination of mortality data.

Adult↗
PubMed1996

[Critical shortage of personnel in nephrology. Assessment of causes of the crisis and suggestion for solution].

The heavier work load for qualified nephrologists in Norway over the last ten years is described and compared with the number of positions. The increase in the number of dialysis treatments, care of renal transplant patients and other tasks performed by qualified nephrologists is roughly doubled from 1985 to 1995. By contrast the number of employed qualified nephrologists to pursue the work has only increased by 20% over the same period. As of today there is a lack of capacity to educate new nephrologists to fill up forthcoming vacancies. When the actual need for nephrologists is taken into account, the discrepancy is much more serious and will become even more so over the next ten years if no immediate action is taken. We suggest the establishment of six new educational positions. Altogether, these six new positions will provide the capacity to educate a reasonable number of trained nephrologists to meet future challenges, to the benefit of patients.

Adult↗
PubMed1996

Overexpression and mutations of p53 in metastatic malignant melanomas.

Alterations of the p53 tumor suppressor gene are the most frequent genetic abnormalities in human malignancies, but the role of p53 in the etiology of malignant melanomas is unclear. Fifty unselected malignant melanomas were analyzed for p53 overexpression by immunohistochemistry using 3 monoclonal antibodies (MAbs). Fifteen tumors (29.4%) showed positive staining with at least 2 different antibodies. In the first 20 consecutive tumors exons 5-9 and adjacent splice sites of the p53 gene were analyzed by genomic sequencing. There were 4 mutations in 20 metastatic melanomas. Three of 4 mutations were C:G-->T:A transitions. A search of our database of p53 mutations revealed that out of 8 p53 mutations reported by others, 4 are C:G-->T:A transitions at dipyrimidine sites, and one is a tandem CC-->TT mutation. This mutational pattern is comparable with the pattern of p53 mutations in squamous cell and basal cell carcinomas of the skin and is related to exposure to ultraviolet B (UV-B) wavelength radiation. Taken together with a predominance of UV-induced mutations in the CDKN2/ p16 gene demonstrated in melanoma cell lines, our data support a role of sunlight exposure in the etiology of malignant melanoma. The low frequency of p53 mutants in melanomas compared with other types of skin cancers suggests that although mutations in this gene are likely to be involved in the development of some malignant melanomas, they do not play as large a role as in squamous and basal cell carcinomas of the skin.

Genes, p53↗
PubMed1996

Half dose of OKT3 is efficient in treatment of steroid-resistant renal allograft rejection.

Rejection episodes in renal allograft recipients are usually efficiently treated with high doses of intravenous methylprednisolone. Rejection therapy with OKT3 is often reserved for steroid-resistant episodes. However, the optimal dose of OKT3 in the treatment of steroid-resistant rejection is not known. Therefore, we randomized renal transplant recipients with steroid-resistant rejection to treatment with a standard daily intravenous dose of either 5 mg of OKT3 (n=15) or 2.5 mg of OKT3 (n=15) for 10 days. Circulating T cells (measured as CD2+ cells) were adequately and equally depleted in the two groups. Three grafts were lost due to rejection within the first 3 months following OKT3 administration, one in the 2.5 mg OKT3 group and two in the 5 mg OKT3 group. Two nonimmunologic graft losses occurred in the 2.5 mg OKT3 group. Median serum creatinine values were not different between the two groups, neither at the start (median values: 200 micormol/L in the 5 mg OKT3 group vs. 188 micromol/L in the 2.5 mg group) nor immediately after OKT3 rescue therapy (202 micromol/L vs. 185 micromol/L, respectively). Eight cytomegalovirus infections occurred in each group. Two re-rejection episodes occurred in the 5 mg OKT3 group and one occurred in the 2.5 mg OKT3 group. All responded to treatment. Function of the remaining grafts estimated by serum creatinine after a mean long-term follow-up of 18 months (range, 6-36 months) revealed no differences (185 micromol/L in the 5 mg OKT3 group vs. 170 micromol/L in the 2.5 mg OKT3 group). We conclude that OKT3 treatment of steroid-resistant rejections in renal transplant recipients is equally effective in daily doses of 2.5 mg and 5 mg with respect to reversal rate and long-term outcome.

Adult↗
PubMed1996

[Radiotherapy of primary non-Hodgkin lymphoma of the stomach].

Primary gastric non Hodgkin's lymphoma is a localized disease, which tends to local recurrences. Local treatment by surgery and/or radiotherapy is adequate for small low malignant primary gastric lymphomas of stages IE and IIE. Larger tumors should be resected before radiotherapy and systemic treatment. Chemotherapy alone has its impact in high grade lymphomas and as adjuvant treatment for tumors < 5 cm. Prospective randomized studies are underway to establish the respective role of the treatment modalities. The radiotherapeutic technique for gastric lymphomas is outlined. The risk of blocking part of the tumor volume by shielding the kidneys is mentioned.

Chemotherapy, Adjuvant↗
PubMed1996

Mutation detection by highly sensitive methods indicates that p53 gene mutations in breast cancer can have important prognostic value.

Human cancer cells with a mutated p53 tumor-suppressor gene have a selective growth advantage and may exhibit resistance to ionizing radiation and certain chemotherapeutic agents. To examine the prognostic value of mutations in the p53 gene, a cohort of 90 Midwestern Caucasian breast cancer patients were analyzed with methodology that detects virtually 100% of all mutations. The presence of a p53 gene mutation was by far the single most predictive indicator for recurrence and death (relative risks of 4.7 and 23.2, respectively). Direct detection of p53 mutations had substantially greater prognostic value than immunohistochemical detection of p53 overexpression. Analysis of p53 gene mutations may permit identification of a subset of breast cancer patients who, despite lack of conventional indicators of poor prognosis, are at high risk of early recurrence and death.

Alternative Splicing↗
PubMed1996

Database of mutations in the p53 and APC tumor suppressor genes designed to facilitate molecular epidemiological analyses.

Germline and somatic mutations in the p53 and APC genes contribute to neoplasia. The patterns of these and other acquired mutations in cancers reflect environmental mutagens and endogenous factors that contribute to carcinogenesis. Herein, we describe a database of almost 2,300 mutations in the p53 and APC genes published until September 1, 1993. In addition to cataloging the mutations, multiple fields of information have been added to facilitate future molecular epidemiological analyses of human cancer. The accuracy of the database has been checked by the present authors and, by soliciting feedback from the original corresponding authors. The strengths and limitations of the primary literature are discussed.

Computer Communication Networks↗
PubMed1996

Effect of arsenic and cadmium on the persistence of mutagen-induced DNA lesions in human cells.

The alkaline single cell gel electrophoresis (SCG test or comet assay) was used to characterize the influence of sodium arsenite (NaAsO2) and cadmium sulphate (CdSO4) on the persistence of mutagen-induced DNA lesions. Human blood and SV4O-transformed fibroblasts (MRC5CV1) were treated for 2 hr with methyl methanesulphonate (MMS) or benzo(a)pyrene (BaP). MMS induced concentration-related DNA damage in white Blood cells (WBC) and fibroblasts in similar concentrations. For the induction of DNA damage in white blood cells (WBC) and fibroblasts in similar concentrations. For the induction of DNA damage by BaP, higher concentrations had to be applied to WBC than to the fibroblast cell line. To study the influence of metal ions on the persistence of DNA lesions, treated cells were further incubated for 2 hr in the absence (postincubation) or presence (posttreatment) of NaAsO2 or CdSO4. After postincubation, MMS and BaP-induced DNA effects were reduced in both cell types, indicating that repair of DNA lesions had taken place. When the cells were posttreated with NaAsO2 or CdSO4, BaP- and MMS-induced DNA lesions persisted in both cell types, indicating an inhibition of DNA repair by these metals. The results suggest a strong interaction of arsenic and cadmium with BaP- and MMS-induced DNA repair processes.

Arsenites↗
PubMed1996

A polymorphism but no mutations in the GADD45 gene in breast cancers.

The p53 gene product is part of a pathway regulating growth arrest at the G1 checkpoint of the cell cycle. Mutation of other components of this pathway, including the products of the ataxia telangiectasia (AT), GADD45, mdm2, and p21WAF1/CIP1 genes may have effects comparable to mutations in the p53 gene. The GADD45 gene is induced by ionizing radiation and several DNA-damaging xenobiotics. Induction requires the binding of wild-type p53 to an evoulutionarily highly conserved putative intronic p53 binding site in intron 3 of GADD45. We recently analyzed the entire coding region of the p53 gene in primary breast cancers of Midwestern white women and found 21 mutations among 53 tumors (39.6%). We now have shown by direct sequencing that there are no mutations in the intronic p53 binding site of the GADD45 gene in any of the 53 primary breast cancers and no mutations in the entire coding region of the GADD45 gene in a subset of 26 consecutive tumors (12 with p53 mutation and 14 without p53 mutation). The only sequence variation detected was a common polymorphism in intron 3. The absence of mutations in the GADD45 gene, including the putative p53-binding intronic site, suggests that this gene is not a frequent target of mutations in breast cancer. Although mutations of the p53 gene have been studied in a wide spectrum of human cancers, GADD45 has not been examined in any tumor or cell line to the best of our knowledge. Our results raise the possibility that mutation of the GADD45 gene alone is not functionally equivalent to loss of wild-type p53 activity.

Base Sequence↗
PubMed1996

18F-fluorodeoxyglucose-PET and 99mTc-bicisate-SPECT in Creutzfeldt-Jakob disease.

In a patient with the occipitoparietal form of Creutzfeldt-Jakob disease (CJD) (Heidenhain type) positron emission tomography (PET) demonstrated decreased glucose utilization in the occipital lobes and adjacent cortical regions. Single photon emission computed tomography (SPECT) with 99mTc-bicisate showed a "coupled" decrease in blood flow in identical cortical areas in this patient. In contrast, magnetic resonance imaging (MRI) was normal. In the early stage of CJD, when still no major morphological abnormalities can be observed, functional imaging is useful for differential diagnosis, particularly to exclude other causes of dementia or pathological EEG patterns.

Aged↗