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Biomedical subjects

V Grimm

Publications and source records attributed to V Grimm.

18 recordsLinked to original sources

New approaches to the isolation of DNA by ion-exchange chromatography.

The performance of different anion-exchange media have been compared for the isolation of plasmid DNA and genomic DNA from bacterial cells and human whole blood. Whatman DEAE-Magarose, based on an agarose bead containing a paramagnetic component, has been compared with prepacked gravity-flow columns containing a derivatised silica matrix. In each case the DNA isolation at various scales of operation was similar both in terms of yield and quality. The magnetic susceptibility of DEAE-Magarose is very high, facilitating the use of this separation technique for rapid flexible batch chromatographic processes, a limitation of the prepacked column techniques.

Chromatography, Ion Exchange↗

Microsatellite instability and loss of heterozygosity in gastric carcinoma in comparison to family history.

We compared 29 gastric carcinomas from patients with a variably strong family history for gastric cancer (group 1) with 36 gastric carcinomas from patients without a family history of this disease (group 2) for microsatellite instability (MSI) and loss of heterozygosity (LOH) with 12 microsatellite markers. Both study groups had similar proportions of histological types and tumor locations. Widespread MSI (alterations at > or = 6 loci) was seen in 5 of 29 (17%) of the tumors belonging to group 1 and in 4 of 36 (11%) group 2 tumors. MSI at a low level (alterations at 1 to 3 loci) was observed in 12 of 29 (41%) of tumors in group 1 and in 10 of 36 (28%) of tumors in group 2, differences that were not statistically significant. A significant difference with respect to low level MSI was observed between the two groups when considering the overall mutation rate of microsatellites. Seventeen of 281 (6%) analyzed microsatellite loci showed alterations in group 1 and 11 of 381 (2.9%) in group 2 (P = 0.046). Comparison of both types of MSI to the clinicopathological parameters in both groups revealed a significant association of low level MSI with advanced tumor stages (P = 0.046) in the group 2, whereas no such association was observed in group 1. In respect to LOH, a significant difference between the two groups was observed at chromosome 17p12, as 13 of 22 (59%) informative cases of group 1 showed LOH in comparison with 7 of 26 (27%) (P = 0.024) in group 2. No correlation of LOH at chromosome 17p12 to the pathological or clinical data was observed either in the two groups or in the study as a whole. Our data show that gastric carcinomas of patients with a positive family history of gastric cancer in group 1 are characterized by a higher mutation rate in respect to low level MSI, particularly at dinucleotide repeats, and by a higher frequency of LOH at chromosome 17p12, indicating that different genetic pathways are involved in the pathogenesis of gastric carcinomas arising in patients with and without a familial background of this disease.

Adult↗

Pattern formation triggered by rare events: lessons from the spread of rabies.

Understanding of large-scale spatial pattern formation is a key to successful management in ecology and epidemiology. Neighbourhood interactions between local units are known to contribute to large-scale patterns, but how much do they contribute and what is the role of regional interactions caused by long-distance processes? How much long-distance dispersal do we need to explain the patterns that we observe in nature? There seems to be no way to answer these questions empirically. Therefore, we present a modelling approach that is a combination of a grid-based model describing local interactions and an individual-based model describing dispersal. Applying our approach to the spread of rabies, we show that in addition to local rabies dynamics, one long-distance infection per 14000 km2 per year is sufficient to reproduce the wave-like spread of this disease. We conclude that even rare ecological events that couple local dynamics on a regional scale may have profound impacts on large-scale patterns and, in turn, dynamics. Furthermore, the following results emerge: (i) Both neighbourhood infection and long-distance infection are needed to generate the wave-like dispersal pattern of rabies; (ii) randomly walking rabid foxes are not sufficient to generate the wave pattern; and (iii) on a scale of less than 100 km x 100 km, temporal oscillations emerge that are independent from long-distance dispersal.

Animals↗

Analysis for microsatellite instability and mutations of the DNA mismatch repair gene hMLH1 in familial gastric cancer.

We examined 30 gastric-cancer patients with a varying degree of family history of stomach cancer and/or synchronous gastric tumors for microsatellite instability. We observed microsatellite instability at at least 1 of 8 loci tested in tumors of 14/30 patients; of these 14, 8 had single locus alterations and 6 had alterations at at least half of the 8 loci. Among the patients with microsatellite instability at > or = 4 loci, 3 patients showed a strong familial clustering of gastric cancer. Mutation analysis of the DNA mismatch repair gene hMLHl on paired non-tumorous and tumor DNA from 10 patients, 6 with microsatellite instability at > or = 4 loci and 4 with an alteration at one locus, revealed a novel missense mutation, present in the normal and tumor DNA of one patient with microsatellite instability at multiple loci in his tumor. His family history of cancer included one second-degree relative affected with gastric cancer. These data suggest that germline mutations in the hMLHl gene occur in some gastric-cancer patients and that in the majority of cases microsatellite instability in gastric tumors may be due to defects in other genes responsible for DNA replication fidelity than the hMLHl.

Adaptor Proteins, Signal Transducing↗

[Patent foramen ovale and platypnea after pneumonectomy].

Six months after a pneumonectomy for myeloma, which had preoperatively been indistinguishable from bronchial carcinoma, a 50-year-old man presented with shortage of breath, cyanosis and episodes of syncope on standing or walking, symptoms which improved on lying down (platypnea). On one occasion these symptoms necessitated controlled artificial ventilation, but even at an inspiratory oxygen saturation of 100%, blood gases only partially improved (pCO2 27 mm Hg, pO2 67 mm Hg, O2 saturation 93%). Right heart catheterization in recumbency revealed a right to left shunt at atrial level of 37% of systemic flow. Contrast medium injection into the inferior vena cava near the heart demonstrated cardiac displacement and rotation. Part of the inferior vena cava flow passed into the left atrium via a patent foramen ovale: it is likely that this shunt increased in the upright position. After surgical closure of the patent foramen ovale and partial relocation of the heart (with a vicryl net) the patient has now remained free of symptoms for 5 years.

Dyspnea↗

Pre-natal administration of diazepam improves radial maze learning in mice.

A number of studies have found that the peri-natal exposure of rodents to diazepam alters their adult behaviour. Adult male mice, treated with diazepam or appropriate controls during pregnancy, were examined in terms of their ability to learn a radial maze. Those animals receiving diazepam prior, but not after birth, learnt the maze significantly more rapidly. The results are discussed in terms of the possible involvement of the hippocampus in this influence of diazepam.

Age Factors↗

[Chemotherapy of the non-small cell carcinoma of the lung with ifosfamide and cisplatin].

80 patients with inoperable non-small cell bronchial carcinoma were treated, at an interval of 4 weeks between them, with ifosfamide (2 g/m2 on days 1-5) and cisplatin (75 mg/m2, day 1). All diagnoses had been confirmed histologically. The course of 72 patients (36 with squamous carcinoma, 25 with adenocarcinoma, two with alveolar-cell carcinoma and nine with large-cell carcinoma) could be evaluated. There were four complete and 21 partial remissions (response rate 35%). In a further 14 patients temporary arrest of tumor growth was registered. Median survival time of all patients was 8.3 months, for those with complete and partial remission 11.5 months. Patients in whom the tumor progressed lived on average 3.9 months. Age and general state of the patients, as well as histological tumor type, had no influence on the results of treatment. Patients in stage IV lived, at seven months, significantly less long than those with only loco-regional spread (11 months). Main side-effects were vomiting, bone-marrow depression and neuropathy. Urotoxicity was not significant, as a result of treatment with mesna. Remission rate and survival time of these patients corresponded with the results obtained with other cisplatin combinations.

Adenocarcinoma↗

Behavioural examinations of the anti-aggressive drug fluprazine.

The behavioural influence of the anti-aggressive drug Fluprazine (DU 27716) was examined using an ethological technique. The drug inhibited aggressive behaviour but not in an entirely specific way. Fluprazine also stimulated non-social and defensive/flight behaviours; there was a greater tendency for drug-treated animals to avoid their opponents. Using an automatic recording technique the drug's anti-aggressive action was monitored for 23 h. There was a potent anti-aggressive influence that lasted for up to 4 h. However, when the drug-effect wore off there were bouts of fighting. Over 23 h Fluprazine did not significantly decrease the total aggression recorded.

Aggression↗

[Thyroid function in premature infants of different gestational age during the first month of life (author's transl)].

To assess the function of the thyroid gland in premature infants of different gestational ages during the first month of life we determined simultaneously TSH, T4, T3, and rT3 serum concentrations in 116 preterm infants (gestational ages 31st to 38th week) during each of the first 30 days of life. The serum concentrations of TSH, T3, and rT3 changed significantly during this period. The TSH and rT3 values were highly increased on the first day and decreased thereafter. The T3 values, however, increased significantly during this period. During the first month of life the T4 values remained roughly unchanged independent of the age of the children. There was no significant influence on serum concentrations of thyroid hormones by gestational age. The 65 preterm infants with adaptational disorders showed no difference in their patterns of TSH and thyroid gland activity during the first month of life compared with 51 healthy premature infants. From the 4th to the 6h day of life -- a recommended period for the screening of congenital hypothyroidism -- the differences of TSH values measured were insignificant (16-18 muU/ml). The T4 values on these days remained all above 6.8 microgram/dl.

Humans↗

A double-blind comparison of melperone and thiothixene in psychotic women using a new rating scale, the CPRS.

Eighty-one women with psychosis of schizophrenic and paranoid type were assigned to a double-blind study comparing the clinical effects of melperone (100 mg X 3) and thiothixene (10 mg X 3). The antipsychotic effect was evaluated by clinical rating according to the CPRS and the NOSIE-30 scales before and after 2 and 4 weeks of drug treatment. A satisfactory interrater reliability was obtained for the CPRS. Significant correlation was also found between the CPRS and NOSIE ratings. Treatment with both drugs was associated with significant reductions in morbidity as estimated by several measures of therapeutic effect from the CPRS, by the NOSIE scale and by global ratings. There were no marked differences at any rating time point between the drugs in this regard. There were more extrapyramidal side effects in the thiothixene group than in the melperone-treated patients. The results encourage the use and further evaluation of melpherone in the treatment of psychotic patients.

Antipsychotic Agents↗

The level of GABA in the brain and locomotor behavior.

GABA content was measured in the brains of animals injected with AOAA, DPA or Saline. Significant increases in GABA were found in the motor cortex and cerebellum after treatment with both drugs as compared to saline injected controls. Increased GABA levels were associated with interference with the smooth execution of locomotor acts, especially where balancing and coordination of the hind limbs were necessary.

Aminobutyrates↗

Urinary kidney-derived antigens determined by tests built on monoclonal antibodies: new markers for kidney damage.

We have developed a series of sandwich ELISA for the quantitation of kidney derived urinary antigens (UA) utilizing monoclonal antibodies specific for antigens localized in cells of defined subunits of the nephron of human kidney. Antigens derived from the distal and proximal parts of the tubular system as well as antigens localized over its entire length can be detected and quantified in urine samples. Antigen excretion was measured in the urine of healthy individuals, patients with various diseases with and without kidney involvement, kidney transplant recipients, and healthy volunteers after receiving antibiotics. Low antigen excretion values were found in healthy individuals, patients with diseases primarily affecting the glomerulus, and inactive phases of chronic diseases. Toxic side effects of drugs were reflected by slightly (antibiotic drugs) or strongly (cytostatic drugs) enhanced antigenuria. Excretion of some or all of the antigens was always indicative of massive alteration of tubular structures, such as in acute phases of tubulointerstitial disease or during rejection episodes in kidney transplant recipients. The results obtained indicate that it is possible to obtain information on the location and extent of acute primary processes in the kidney with these tests.

Antibodies, Monoclonal↗