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J Althoff

Publications and source records attributed to J Althoff.

At least 19 recordsLinked to original sources
PubMed2002

Workshop report. Children as a special subpopulation: focus on immunotoxicity. Federal Institute for Health Protection of Consumers and Veterinary Medicine (BgVV), 15-16 November 2001, Berlin, Germany.

An international symposium on the impact of environmental hazards, chemicals and drugs on the developing immune system of children was held in Berlin (Germany) organized by the BgVV. Epidemiological evidence indicates that an immature immune system challenged early in life by bacterial antigens may prevent, to some extent, allergic reactions including asthma bronchiale triggered by environmental pollutants. However, the prevalence for infectious disease is increased in childhood, especially when exposure to contaminants takes place in the period of pregnancy and breast-feeding. The effects of chlorinated biphenyls, dioxin, endotoxins, hexachlorobenzene, and direct and indirect in utero tobacco smoke exposure are examples. All participants recommend comparative and follow-up epidemiological studies and clinical examination of infants and children at risk during upbringing. There is ample evidence from experimental studies that indicates adverse effects on the developing immune system after in utero and postnatal exposure to chemicals and drugs. The adverse reactions of aciclovir, benzodiazepines, hexachlorobenzene, organotins (di-n-octyltin dichloride, tributyltin oxide), pesticides (methoxychlor, heptachlor) and polyhalogenated aromatic hydrocarbons (2,3,7,8-tetrachlorodibenzo-p-dioxin) are presented and reviewed. To determine the predictive value of test data in risk assessment for neonates and children, development, differentiation and maturation of the immune system in humans and laboratory rodents is compared in their pre- and postnatal stages. Considering some differences in immunocompetence at birth and after lactation, and differences in the time frame for maturation of the immune system, reaction types are thought to be common, comparable and similar in human childhood and early adolescence and the postnatal lifetime of laboratory rodents. The participants of the symposium felt strongly that regulatory steps urgently need to be initiated to incorporate some relevant aspects into existing test guidelines for testing developmental immunotoxicity. In this context, it is recommended that animals culled otherwise in one- and two-generation studies be examined for developmental immunotoxicity according to the valid methods and parameters discussed. The majority of participants agreed that a safety factor of 10 is too low in risk assessment and management to protect a sensitive subpopulation of children against man-made environmental pollutants.

Animals↗
PubMed2000

Capillary electrophoresis and off-line capillary electrophoresis-electrospray ionization quadrupole time-of-flight tandem mass spectrometry of carbohydrates.

The use of off-line high-performance capillary electrophoresis in connection with nanospray electrospray ionization quadrupole time-of-flight tandem mass spectrometry for identification of complex carbohydrates of biological origin is presented. The method was applied to the identification of O-glycosylated amino acids and -glycopeptides from the urine of patients suffering from a hereditary disease - N-acetylhexosaminidase deficiency. Structural elements typical for O-glycosylation of proteins, like expression of core 1 and 2 type O-glycans with different numbers of N-acetyllactosaminyl repeats and different degrees of sialylation, can be directly detected.

Carbohydrate Sequence↗
PubMed1999

Animal model of experimentally induced ectopic enchondral ossification in nude mice with xenograft of porcine epiphyseal cartilage.

In a specific animal model the induction of heterologous enchondral ossification was examined in long term follow-up. Physiologically normal and devitalized frozen porcine epiphyseal cartilage as a control group were transplanted as s.c. xenograft into athymic nude mice (nu/nu). 15 weeks after transplantation the porcine growth plate cartilage showed the development of viable cartilage tissue in the recipients, further differentiating to juvenile long bone with epiphysis, diaphysis and growth plate. Porcine growth plate cartilage increased s.c. in the recipient nude mice, showing enchondral ossification without any physiological load, and finally an unexpected development towards complete juvenile long bone.

Animals↗
PubMed1999

Dilated cardiomyopathy of Doberman pinschers: retrospective histomorphologic evaluation of heart from 32 cases.

Dilated cardiomyopathy of Doberman Pinschers (DCDP) is a progressive disease often presenting with a history of episodic weakness and syncope, or with clinical signs of predominantly left-sided congestive heart failure. A systematic dissection and histomorphologic evaluation of the heart from 32 Doberman Pinschers with a clinical diagnosis of dilated cardiomyopathy revealed a highly specific location for the characteristic myocardial lesions. The lesions of DCDP were found only in the left ventricular free wall, and in 30 cases, the lesions were characterized by myofiber degeneration and atrophy, and replacement of myocardium by dense bundles of collagen and clusters of adipocytes. In the two remaining hearts, myofiber atrophy and degeneration were accompanied by collagen deposition, but not adipocytes. In stained longitudinal (base to apex) tissue sections of the left ventricle, the lesions of DCDP were usually apparent to the unaided eye; appearing as a central linear pale zone, aligned in the long axis of the ventricular free wall. The lesions did not contain inflammatory cell infiltrates and often involved > 50% of ventricular wall.

Animals↗
PubMed1996

Difference between guinea pig and rat in the liver peroxisomal response to equivalent plasmatic level of ciprofibrate.

Guinea pig was previously classified as a species nonresponsive to peroxisome proliferators. However, none of the previous reports was based on pharmacokinetic data. Here, after a comparative pharmacokinetic study between the guinea pig and rat, we evaluate the guinea pig liver peroxisomal response to ciprofibrate, a hypolipemic agent and a potent peroxisome proliferator in rat. (1) Pharmacokinetic results show equivalent in guinea pig and rat when guinea pigs are treated with ciprofibrate at 30 mg/kg twice a day and rats are treated at 3 mg/kg once a day. (2) The treatment of guinea pigs at 30 mg/kg twice a day for 2 weeks leads to a significant increase in the liver peroxisomal palmitoyl-CoA oxidase activity (x 1.6) and also in the microsomal omega-laurate hydroxylase activity (x 1.8). These increases are in accordance with the changes in polypeptide patterns of isolated liver peroxisomes as well as in the immunoblotting of acyl-CoA oxidase. It is deduced that a weak, but significant, peroxisome proliferation can occur in guinea pig liver after a ciprofibrate treatment at dosages corresponding to equivalent plasmic concentrations of the drug between guinea pig and rat. (3) The hybridization of guinea pig liver RNA with the rat liver-inducible acyl-CoA oxidase cDNA probe shows a decrease in the corresponding heterologous mRNA content after treatment with ciprofibrate at 30 mg/kg twice a day. This result contrasts with the slight increase observed in immunodetection and in enzymatic assays, suggesting the existence of at least two different acyl-CoA oxidases in guinea pig liver peroxisomes.

Acyl-CoA Oxidase↗
PubMed1995

Tissue differentiation and correlated changes in enzymatic activities during primary antler development in fallow deer (Dama dama).

BACKGROUND: Deer antlers are useful models for studying bone growth and biomineralization in mammals. To achieve a better understanding of the mechanisms underlying the formation of primary cranial appendages in deer, the present study relates the histogenesis of primary antlers to changes in enzymatic (phosphatase) activities in the different tissue zones of this organ. METHODS: The growing tips of the primary antlers (4.3 to 5 cm in length) were removed from five fallow bucks, aged about 10 months. Part of the material was processed for light microscopy. The other part was cryofixed, and the different histologically defined regions were analyzed for the activities of alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) as well as for the concentrations of inorganic and organic phosphate. RESULTS AND CONCLUSIONS: Histologically, the primary antler could in distoproximal direction be divided into eight different zones (dermis; perichondrium; zones of cartilage formation, hypertrophy, mineralization, and degeneration; primary spongiosa; secondary spongiosa). The histological results demonstrate that the elongation of the primary antler proceeded through a modified form of endochondral ossification, resembling that seen during formation of pedicles and secondary antlers. The concentrations of the extractable activities of ALP and TRAP progressively increased from the perichondrium to the zone of cartilage mineralization. Thus, highest activity of TRAP during primary antler formation occurred at an earlier stage of tissue differentiation than in somatic endochondral ossification, where the enzyme is a biochemical marker of osteoclastic activity during bone remodeling. The present results might reflect the presence of osteoclastic precursor cells in the zone of cartilage mineralization as an adaptation to the rapidity of antler growth. Our findings of the contents of extractable ALP, inorganic and organic phosphate in the different tissue zones of the developing primary antler are in good agreement with previous studies analyzing epiphyseal growth plates and point to the fact that ALP causes a rise in inorganic phosphate and the removal of inhibitors for mineralization, like pyrophosphate.

Acid Phosphatase↗
PubMed1994

Biochemical and histological study of the ossification in the early developing pedicle of the fallow deer (Dama dama).

To date, no histochemical data exist concerning the process of ossification of developing pedicles in deer. Four different zones of the growing pedicle (subcutaneous tissue; fibrous layer of the periosteum; cambial layer of the periosteum; woven bone of the primary spongiosa) were analysed in direct correlation to their histological appearance. The level of extractable specific alkaline phosphatase in the preosseous zones of the pedicle was 4-fold higher than levels in the epiphyseal growth plate previously reported. These results reflect that rapid bone formation takes place in the growing pedicle. Highest buffer-extractable alkaline phosphatase activity was found in the cambial layer directly in front of the mineralization area of the pedicle-bone, connected with maximal values for organically bound phosphate and inorganic phosphate. Moreover, the values for buffer-extractable alkaline phosphatase, organically bound phosphate and inorganic phosphate decreased with increasing mineralization in the zone of the primary spongiosa. The present histological and biochemical findings on the process of ossification in the pedicle show similarities to typical endochondral ossification. The process of pedicle growth may serve as a new and important system for chondrogenic and osteogenic studies, including a better understanding of antler development.

Alkaline Phosphatase↗
PubMed1991

Effects of age and gender on fat-induced gallbladder contraction and gastric emptying of a caloric liquid meal: a sonographic study.

In this study, the gastric emptying of a liquid fatty meal and the consecutive gallbladder contraction were simultaneously measured by ultrasound in four different age- and sex-related groups of normal subjects: group A, 15 women less than 50 yr (premenopausal); group B, 15 women greater than 50 yr (postmenopausal); group C, 15 men less than 50 yr; and group D, 15 men greater than 50 yr. Apart from a significantly delayed gastric emptying in the premenopausal women, no significant differences in the postprandial relative gallbladder emptying rates were observed between the four study groups. Ninety-five percent of all study subjects had a gallbladder volume reduction of more than 50% after a liquid fatty meal. It is therefore concluded, that 1) endogenous or contraceptive female sex hormones may have a delaying effect on gastric emptying of caloric liquids in the premenopausal state, 2) aging or gender do not significantly influence the fat-induced gallbladder contraction in man, and 3) a 50% residual volume of the gallbladder after a fatty meal should be considered as the upper limit of normal gallbladder contractility (95 percentile of a normal collective).

Adult↗
PubMed1986

Cemento-fibrous dysplasia of the periodontal membrane (studies of the European hamster maxillary incisor).

The periodontal membrane of European hamster maxillary incisors showed histologic changes consisting of an irregularly orientated, less vascularized connective tissue which included abundant cementicle-like structures. The changes were multifocal and bilateral, growing towards the alveolar bone (Grade 1), causing atrophy of the alveolar bone due to compression (Grade 2) and reaching the periosteal membranes (Grade 3). In a few animals, the lesions were seen after one year. They were seen in 80% of hamsters more than 2 years old. Carcinogenic exposure did not alter the latency and incidence of the alterations. The lesions were thought to be a spontaneously occurring disease representing a nodular cemento-fibrous dysplasia of the periodontium. As, morphologically, no exact attribution to other odontogenic or mesenchymal growth could be made, the entity of this periodontal lesion was considered. Although the changes observed in the periodontal membrane of the maxillary incisors of the European hamster were not exactly comparable to odontogenic cemental lesions in man, they may serve as a model to further clarify the nature of fibro-osseous lesions.

Alveolar Process↗
PubMed1985

Comparative study on the carcinogenicity of N-nitroso-2,6-dimethylmorpholine in the European hamster.

The effect of N-nitroso-2,6-dimethylmorpholine (NDMM), a pancreatic carcinogen for the Syrian golden hamster, was examined in the European hamster (EH) for comparative reasons. The compound was administered by subcutaneous (SC) injection or intragastric gavage (IG) at a dose level corresponding to 0.1 of LD50. In terms of carcinogenicity the main target was the respiratory epithelium (nasal cavity, lung, trachea, larynx); other benign and malignant tumors originated in the liver (bile duct epithelium and endothelium) and renal pelvis (transitional epithelium). The occurrence of neoplasms seen at other sites was difficult to attribute to treatment. Reduced metabolism as found during hibernation did not change the organ distribution of neoplastic growths. Differences in the carcinogenic potency (tumor incidence and latency, affected organs and cell types) did not depend significantly on the route of administration. The data were compared to those obtained using other nitroso compounds in this species.

Animals↗
PubMed1985

The influence of metabolic liver defects on diethylnitrosamine (NDEA)-carcinogenesis in Gunn rats.

Diethylnitrosamine (NDEA) was administered subcutaneously to non-icteric and icteric Gunn rats. A single dose led predominantly to liver cell tumours. The average survival times and tumour latencies were not dose dependent, but a slightly raised tumour multiplicity was observed in icteric animals. The minimal effective dose was apparently less than 0.05 LD50 and more than 0.025 LD50. Chronic treatment in Gunn rats revealed dose response relationships for body weight development, average survival times and tumour latencies. The most common tumours found in the liver of both non-icteric and icteric animals were hepatocellular neoplasms followed by cholangiocellular tumours and haemangio-endotheliomas. Neoplastic growth was also found in the respiratory tract and upper digestive tract. The maximal effective carcinogenic dose for non-icteric and icteric rats was 0.1 LD50. The carcinogenic effect of NDEA in Gunn rats was only marginally influenced by the changes in the liver associated with icterus.

Adenoma↗
PubMed1985

Ultrastructural aspects of oral and facial lepromatous lesions.

The ultrastructure of 10 lepromatous lesions in the face and the palatal mucosa after different duration and length of treatment was studied. Biopsies taken from patients who showed erythema nodosum leprosum (ENL) revealed different ultrastructural characteristics from those taken from 'burnt out' and non-medicated cases. Multiple secondary lysosomes were rarely seen in non-ENL cases. The presence of Mycobacterium leprae and an increased lysosomal activity in ENL reactive cases is interpreted as a reaction to the lysis of the cytoplasmic matrix of M. leprae; however, drug-specific (diaminodiphenylsulphone) reactions must also be considered.

Adolescent↗
PubMed1985

Biological characterization of human bone tumors. IV. Combined biochemical and histological analyses of different osteosarcomas.

A new technique was applied to the study of human osteosarcoma. Ten slices of 10 micron were cut serially from 2 X 2 X 6 mm shock frozen blocks of human osteosarcoma for chemical analysis. Before and after each series of 10 slices, one slice of 10 micron was separated for morphological analysis. Four different types of osteosarcoma were investigated: Case 1 was an atypical osteoblastic osteosarcoma, case 2 a small cell sclerosing osteosarcoma, case 3 a well-differentiated parosteal osteosarcoma grade I, and case 4 a highly malignant anaplastic osteosarcoma. Alkaline phosphatase, acid phosphatase, beta-glucuronidase and proteolytic activities were analysed as well as matrix collagen and hexosamine, phosphorus (Pi and Po), protein, DNA, and water content. In accordance with the morphology, the obtained data illustrate the great heterogeneity of osteosarcomas. Although case 1, 2 and 3 all represent calcifying types of the tumor, characteristic differences exist with regard to the matrix and the degree of calcification. In contrast to these three, case 4 presents a noncalcified type of osteosarcoma whose matrix contains relatively high amounts of hexosamine and low amounts of collagen, whereas DNA and water contents are high. The data from the analysis of osteosarcoma were compared with previous results from the calf epiphyseal growth plate in order to define differences and similarities between the formation of tumor bone and the physiological formation of hard tissue.

Acid Phosphatase↗
PubMed1985

Biological characterization of human bone tumors. V. Zonal characterization of osteosarcoma: topological biochemical analysis correlated with morphology.

Human osteosarcoma specimens were sliced in a cryomicrotome under strict morphological guidance. Serial sections of ten 10 micron slices each were collected in two groups according to morphologic criteria, one containing mostly undifferentiated tumor tissue, the other predominantly well-differentiated tumor tissue. The two series were analysed chemically for alkaline phosphatase (APase) acid phosphatase (acPase), beta-glucuronidase and proteolytic activities; protein, phosphorus, hydroxyproline, hexosamine, water and collagen contents were also determined. Four different types of osteosarcoma were studied: case 1 was a highly malignant osteoblastic osteosarcoma, case 2 a small cell sclerosing osteosarcoma case 3 a well-differentiated osteosarcoma, and case 4 a highly malignant anaplastic osteosarcoma. The types of cases 1, 2 and 3 are known as osteoid-forming tumors. In their less well differentiated areas APase activity was about twice as high as in better differentiated osteosarcoma. In contrast, no APase was found in the wholly undifferentiated areas of case 4, while the enzyme showed a marked increase in the areas of incipient differentiation of this tumor. The matrix of tumors differs with regard to collagen and hexosamine contents, in accordance with the general state of differentiation. In general, increasing hexosamine contents together with decreasing hydroxyproline contents will reflect the anaplastic, dedifferentiated osteosarcoma. Calcification evident in the better differentiated areas of osteosarcoma is indicated by the phosphorus content, highest in case 2, with cases 3, 1, and 4 following in sequential order.

Acid Phosphatase↗
PubMed1985

Carcinogenicity of diallylnitrosamine following intragastric administration to Syrian hamsters.

Single and multiple intragastric doses of diallylnitrosamine [(DAN) CAS: 16338-97-9] administered to Syrian golden hamsters induced tumors, primarily of the respiratory tract, in which the nasal cavity epithelium was the preferred site. When compared to the effect of DAN after subcutaneous administration at equal doses, the incidence of respiratory tract tumors was lower but that of hepatic tumors was higher, suggesting partial metabolism of DAN in the liver. Comparative metabolic and mutagenesis studies in BD IX rats (which reportedly are refractory to the carcinogenic effects of DAN), in Wistar rats, and in Syrian hamsters showed that a greater proportion of orally administered DAN was exhaled by both rat strains (12-19%) than by hamsters (2-4%). The activity of the microsomal fraction of the hamster liver for metabolizing DAN to allyl alcohol was about 10 times higher than that in rats, whereas no significant species differences were found with the cytosolic fraction. Pretreatment of animals with phenobarbital (PB) or pregnenolone-16 alpha-carbonitrile (PCN) did not influence either microsomal or cytosolic enzyme activities in hamsters, whereas about a tenfold increase in enzyme activities was seen after pretreatment with PB in both rat strains and following PCN in Wistar rats. Moreover, in bacterial mutagenesis assays, hamster liver microsomes were twice as active as those in BD IX rats. The results are discussed in relation to the carcinogenicity of DAN in rats and hamsters.

Adenocarcinoma↗