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Biomedical subjects

H Hofer

Publications and source records attributed to H Hofer.

At least 37 records · Page 2Linked to original sources
PubMed1999

Biological effects of 1alpha-hydroxy- and 1beta-(hydroxymethyl)-vitamin D compounds relevant for potential colorectal cancer therapy.

1alpha,25-dihydroxyvitamin D(3) and two synthetic analogs, 1alpha, 25-dihydroxy-16-ene-23-yne-vitamin D(3) (Ro 23-7553) and 1alpha, 25-dihydroxy-16-ene-24-oxo-vitamin D(3) (JK-1624-3), were tested for their ability to specifically inhibit growth and promote differentiation of human colon cancer cells in comparison with a series of 1beta-(hydroxymethyl) congeners of the natural hormone, such as 1beta-(hydroxymethyl)-3alpha,25(OH)(2)-16-ene,24-oxo-vitamin D(3) (JK-1624-2), 1beta-(hydroxymethyl)-3alpha, 25-dihydroxy-16-ene-26,27-dihomo vitamin D(3) (JK-1626-2), and 1beta-(hydroxymethyl)-3alpha,25-dihydroxy-22,24-diene-26,27- dihomo vitamin D(3) (MCW-EE). Western blot analysis revealed that reduction of cyclin D1 levels is a key mechanism by which the vitamin D compounds under investigation inhibit Caco-2 tumor cell growth. Both the 1alpha-hydroxy- as well as the 1beta-hydroxymethyl-type vitamin D compounds, which exhibit only low affinity for the vitamin D receptor, significantly reduced [(3)H]thymidine DNA labeling in confluent Caco-2 cell cultures. This suggests that high-affinity binding to the vitamin D receptor is not an absolute prerequisite for genomic action on tumor cell growth. Hybrid analogs JK-1624-2 and MCW-EE, although antimitotically active, were rather ineffective in promoting phenotypic differentiation of human colon cancer cells. However, because both compounds also do not promote osteoclast differentiation from hematopoetic bone marrow cells, they still could be used as antimitotic agents in cancer therapy, even at dose levels that, with other analogs, could cause hypercalcemia.

Acid Phosphatase↗
PubMed1998

Genetic characterization of canine distemper virus in Serengeti carnivores.

The lion (Panthera leo) population in the Serengeti ecosystem was recently afflicted by a fatal epidemic involving neurological disease, encephalitis and pneumonia. The cause was identified as canine distemper virus (CDV). Several other species in the Serengeti were also affected. This report presents CDV H and P gene sequences isolated from Serengeti lions (Panthera leo), spotted hyenas (Crocuta crocuta), bat-eared fox (Otocyon megalotis) and domestic dog (Canis familiaris). Sequence analyses demonstrated that the four Serengeti species carry closely related CDV isolates which are genetically distinct from other CDV isolates from various species and locations. The results are consistent with the conclusions that: (1) a particularly virulent strain of CDV emerged among Serengeti carnivores within the last few years; (2) that strain has recognizable shared-derived (synapomorphic) genetic differences in both H and P genes when compared to CDV from other parts of the world; and (3) that the CDV strain has frequently crossed host species among Serengeti carnivores.

Africa↗
PubMed1998

Growth regulation of human colon cancer cells by epidermal growth factor and 1,25-dihydroxyvitamin D3 is mediated by mutual modulation of receptor expression.

The human colon adenocarcinoma-derived cell line Caco-2 was used as a model system to study the interaction of epidermal growth factors (EGF) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in control of colorectal cancer cell growth. The mitogenic stimulus of EGF was rapidly transduced via apical and basal membrane receptors alike into elevation of c-myc expression, causing a shift of Caco-2 cells from the G0/G1 into the S phase of the cell cycle. The stimulatory effect of EGF on cell division was effectively counteracted by 1,25(OH)2D3: the presence of the steroid hormone prevents the negative effect of EGF on vitamin D receptor abundance and concurrently minimises ligand-occupied EGF receptor numbers on both sides of Caco-2 cell monolayers. Our data suggest that EGF and 1,25-(OH)2D3 actions on mutual receptor levels represent a specific feature of the potent antimitogenic effect of the steroid hormone on colon cancer cells.

Blotting, Northern↗
PubMed1997

IRAG working group 2. CAM-based assays. Interagency Regulatory Alternatives Group.

CAM-based assays, in which test material is applied to the chorion allantoic membrane (CAM) of embryonated chicken eggs, were assessed as alternatives to the Draize eye irritation test. Two general types of CAM-based assays are currently in use, the HET-CAM test and the CAMVA assay. Evaluations were made of five data sets produced with three different modifications of the HET-CAM test and two data sets obtained with the same CAMVA protocol. Data sets consisted of 9-133 test chemicals, usually from the sponsor's product line, and also from a validation trial. Each data set and assay protocol were analysed for quality of data, purpose and proposed use of the assay, range of responses covered, range of test materials amenable, current use in safety and risk assessment both in-house and for regulatory purposes. Since the MMAS Draize score was not available for all in vivo data sets, the sigma MMMIS, which correlates well with the MMAS, was used instead. In vitro/in vivo correlations calculated with Pearson's linear coefficient ranged from r = 0.6 to r = 0.9 for six of seven data sets. Corneal opacity and inflammation of the iris showed the best correlation to in vitro data. Prediction rates were significantly improved when partial linear regression was used, and the predictivity of three different HET-CAM protocols was almost the same. HET-CAM assays showed the best prediction with surfactants and surfactant-based formulations, whereas the CAMVA assay provided the best performance with alcohols.

Allantois↗
PubMed1996

Canine distemper virus infection in Serengeti spotted hyenas.

Clinical signs suggestive of canine distemper virus (CDV) infection were observed among a group of spotted hyenas (Crocuta crocuta) in the Serengeti, Tanzania. Virus antigen was detected immunohistologically in a brain sample from a diseased cub. The presence of virus RNA could be demonstrated in this brain as well as in intestine and lymph node of the animal by RT-PCR. Sequence comparison of brain-derived amplicons showed that the virus was related to recent CDV field isolates. The closest homology (>99 percent) was to a recently described CDV which caused high mortality in sympatric lions.

Animals↗
PubMed1996

Parametric and non-parametric measures in the assessment of knee and hip osteoarthritis: interobserver reliability and correlation with radiology.

The aim of this study was to evaluate the interobserver reliability of parametric and non-parametric variables in the clinical assessment of hip and knee osteoarthritis (OA). Three rheumatologists examined 49 patients with different radiological stages of OA using different assessment tools such as a tape measure, a goniometer, a plurimeter and a hand-held pull gauge. The reliabilities of parametric variables calculated by analysis of variance (ANOVA) showed much higher values than the non-parametric ones calculated by Kendall's tau beta. The highest levels of correlation in hip OA between clinical functional tests and radiological changes were found for hip extension (r = 0.57; P < 0.01) and the Patrick sign (r = 0.54; P < 0.01) while in knee OA the highest correlations were found for knee circumference (r = 0.5; P < 0.01) and knee flexion (r = 0.035; P < 0.02). Knee muscle strength, as measured with a hand-held pull gauge, showed a high level of interobserver agreement (r = 0.79), but correlated poorly with radiological changes. In conclusion parametric variables of joint morphology as knee circumference of parametric variables of function as the Patrick sign should be preferred for assessing secondary endpoints in OA clinical trials.

Aged↗
PubMed1995

Population dynamics, intervention and survival in African wild dogs (Lycaon pictus).

The demography of Serengeti wild dog study packs and their extinction in 1991 was documented by Burrows et al. (1994). One explanation for pack loss compatible with demographic evidence was viral disease induced by stress caused by intervention (vaccination, immobilization and radio-collaring). Several studies claim to reject this hypothesis. However, cortisol levels measured in immobilized Lycaon, whose pathogen exposure is unknown, do not demonstrate that interventions in the Serengeti were benign. The analysis of survivorship in Lycaon in other ecosystems minimized the chance of demonstrating any effect of intervention and failed to consider vaccinations as intervention. There is now evidence that intervention significantly decreased survivorship of Masai Mara Lycaon. Further simulations of the likelihood of population extinction in Serengeti Lycaon, evidence of limited population variability and a small scaling factor in Serengeti Lycaon strengthen Burrows et al.'s conclusion that the extinction was unlikely to be due to chance alone. Although some studies claim that Lycaon conservation is doomed without intervention, to date vaccinations, blood sampling and radio-telemetry have contributed little to Lycaon conservation. All studies fail to disprove the Burrows hypothesis or provide convincing alternatives.

Animals↗
PubMed1994

Demography, extinction and intervention in a small population: the case of the Serengeti wild dogs.

The effects of ecological factors (prey, competitors, predators and disease) and intervention (immobilization, radio-collaring, and vaccination) on population size and demography were investigated in Serengeti wild dogs (Lycaon pictus), an endangered canid, between 1965 and 1991. Variation in ecological factors explained most changes in demography, but did not explain a decline in adult longevity. A significant reduction in pack life and individual longevity was coincident with the introduction of routine intervention and consistent with pathogen-induced mortality. Survival varied significantly between categories of intervention, and between individuals likely to have been exposed to different degrees of social stress before intervention. The loss of all study packs in 1991 contrasted with the persistence of breeding packs outside the study area. The cause of the demise of most study packs is unknown. Monte Carlo simulations demonstrated that population extinction was unlikely to be the consequence of chance events alone. One explanation compatible with the evidence is an outbreak of viral disease induced by stress, possibly caused by intervention.

Animals↗
PubMed1994

[A 2-generation fertility study with 1,4-dichlorobenzene in rats].

1,4-Dichlorobenzene (pDCB), dissolved in olive oil, was administered orally to two generations of rats to detect possible effects of the test substance on reproduction (OECD guideline 416). The doses used for the three test substance groups were 30, 90 and 270 mg pDCB per kg body weight. Olive oil was applied to one negative control group. Dose volume was 1 ml per kg body weight for all groups. In both generations the test substance had no effects on: time between beginning of mating and evidence of copulation, time of gestation, fertility index, gestational index, percentage of dams with only dead pups, total number of pups at birth, percentage of pups with positive ear reflex, grasping reflex and orientation reaction, absolute and relative weights of testes, epididymides and ovaries, absolute and relative weights of female kidneys, spleens and livers. In the mid and/or high-dose groups the test substance had an effect on: number of live pups at birth (reduced), number of pups deceased between days of lactation 1 to 4 and 5 to 21 (increased), mean body weight of pups (reduced), erection of ears and opening of eyes (retarded), percentage of pups with positive draw up test (reduced), alterations of the skin (dry, squamous) and ring tails in pups, absolute and relative organ weights of adult males (livers and kidneys: increased; spleens: reduced). Damages to the kidneys in mid- and high-dose groups of both generations are also probably test substance related. At the low dose of 30mg pDCB per kg body weight--equivalent to the actual MAK-value of 450 mg/m3 (exposure by inhalation)--no effects of the test substance were detected on fertility parameters of rats. The next higher dose of 90 mg/kg already caused massive damage in pups. Therefore, a reduction of the actual MAK value should be taken into consideration.

Animals↗
PubMed1993

Isometric maximal and submaximal trunk extension at different flexed positions in standing. Triaxial torque output and EMG.

Thirty-one healthy men were tested for the effects of trunk-flexion positions (0 degrees, 15 degrees, and 35 degrees) in standing on triaxial torques and electromyogram of 10 trunk muscles during voluntary maximal and submaximal isometric trunk extension. At a more flexed position, both erector spinae and latissimus dorsi showed significantly higher RMS-EMG. The abdominal obliques were coactivated only during 100% maximum voluntary exertion at each posture. In all tests, the rectus abdomini were quiet. Mean maximum extension torque increased significantly at 15 degrees and 35 degrees of trunk flexion. The ratio of extension torque over RMS-EMG of the trunk extensor muscles, called the neuromuscular efficiency ratio (NMER), also increased in the more flexed posture. However, NMER has to be interpreted with caution because it is affected both by posture and exertion levels. The effects of posture on the torque generation capability of the trunk question the validity of the current lifting recommendations.

Abdominal Muscles↗
PubMed1983

Skin penetration by 2,4-diaminoanisole in the rat.

The absorption of 14C-labelled 2,4-diaminoanisole together with its reaction products was investigated after application to the skin of rats. 2,4-Diamino[14C]anisole was applied as an ingredient of three different hair-dyeing formulations using procedures approximating to realistic conditions of use. Percutaneous absorption of the compound ranged from 0.26 to 1.1% of the administered dose, according to the formulation used. Elimination occurred mainly in the urine, with a smaller proportion in the faeces. Very small amounts were detected in the expired air. Complementary investigations involving subcutaneous or oral application of a solution of 2,4-diamino[14C]anisole.2HCl showed that radioactivity was rapidly eliminated in the urine and faeces. Biliary excretion was demonstrated after oral administration.

Administration, Oral↗
PubMed1983

Analysis of human chromosomes after repeated hair dyeing.

Ten volunteers (males and females) each had their hair dyed 13 times at intervals of 3-6 wk. Each volunteer used a single commercial preparation throughout the study. The preparations used contained a mixture of aminotoluenes, aminophenols and hydroxybenzenes and, in some cases, naphthol, as the active ingredients. Lymphocytes of the hair-dyed volunteers and of ten controls matched for age and sex were scored for chromosomal aberrations. The incidence of aberrations did not differ significantly between the controls and the hair-dyed volunteers at any of the nine sampling times (before the first exposure, after the first (sham) dyeing and then after each of the next three and the last four dyeing procedures). An increase in the aberration rate with time was observed both in the controls and in the hair-dyed subjects. The reason for this increase could not be determined. No clastogenic effect of repeated hair dyeing was established in this study.

Adult↗
PubMed1982

Percutaneous absorption of 2-amino-4-nitrophenol in the rat.

The absorption of 14C-labelled 2-amino-4-nitrophenol (ANP) in two hair dyeing formulations was investigated after application to the skin of rats. After 1 and 5 days, 0.21 and 0.36%, respectively, of the administered radioactivity was absorbed from formulation 1 which contained carboxymethylcellulose as a thickening agent. Absorption was greater (1.12% after 1 day, 1.67% after 5 days) from formulation 2 which contained oleic acid and isopropanol. Complementary studies of absorption after administration of [14C]ANP by sc injection or oral gavage were also carried out. The radioactivity was rapidly excreted, predominantly in the urine, in both cases. Biliary excretion was also detected in an oral study.

Administration, Oral↗