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Biomedical subjects

J Schmidt

Publications and source records attributed to J Schmidt.

At least 559 records · Page 31Linked to original sources

c-fos expression precedes osteogenic differentiation of cartilage cells in vitro.

We have investigated the temporal pattern of expression of c-fos in cartilage cells in mouse mandibular condyles. During in vitro cultivation, the progenitor cells in this organ differentiate to osteoblasts, and hypertrophic chondrocytes start to show features indicative of osteogenic differentiation. Prior to these processes we observed two distinct patterns of c-fos expression. High, transient c-fos expression was found in the entire tissue within 30 min of culture. This type of c-fos expression appeared to result from mechanical forces applied during dissection. The second type of c-fos expression appeared in individual cells in the zone of hypertrophic chondrocytes. A varying number of formerly quiescent chondrocytes expressed high levels of c-fos mRNA after between 30 min and 10 d in culture, with a peak in the number of cells between days 1 and 3. c-fos expression in these cartilage cells was followed by DNA replication and expression of genes typifying osteoblastic differentiation. After 7 d in culture, groups of cells with the typical ultrastructural features of osteoblasts, and surrounded by an osteoid-like matrix, were observed in single chondrocyte-type lacunae, suggesting division of chondrocytes and differentiation to osteoblasts. The data suggest that c-fos may play a crucial role in the perturbation of determined pathways of skeletoblast differentiation and in the regulation of endochondral bone formation.

Animals↗

Infection of human fibroblasts and osteoblast-like cells with HIV-1.

Primary human skin- and lung-derived fibroblast cell cultures and continuous human osteoblast-like and fibroblast-like cell lines were infected with different strains of HIV-1. Infection was measured at the single-cell level using the immunoperoxidase staining method to detect viral proteins. No cytopathic effects were observed in HIV-1-infected cell cultures. One continuous cell line (LC5), derived from embryonic lung, was readily infectable with HIV-1 and showed continuous production of infectious virus. Infection of LC5 cells could be blocked with anti-CD4 monoclonal antibodies. These findings indicate that fibroblasts of skin and lung, and osteogenic cells may be considered as potential target cells for HIV-1, thereby possibly contributing to the establishment of local HIV reservoirs.

Acquired Immunodeficiency Syndrome↗

Characterization of fos-induced osteogenic tumours and tumour-derived murine cell lines.

Osteogenic tumours from c-fos (MT-c-fos-LTR)-transgenic mice and from mice infected with the v-fos-bearing FBR murine osteosarcoma virus (FBR MSV) showed close morphological and neoplastic similarities. Fos mRNA expression was elevated in both types of tumours, and expression of several genes characteristic of differentiated bone cells was either lower, enhanced, or not detectable in comparison to that in normal bone. Tumour-derived cell lines showed variable levels of exogenous fos expression; bone-cell-specific genes were similarly expressed in both primary tumours and tumour-derived cell lines. Upon transplantation the tumour cells formed fibrosarcomas, some of which contained areas of focal osseochondrous differentiation. Non-tumorigenic cell lines established from bone tissue of normal and MT-c-fos-LTR transgenic mice showed osteoblastic characteristics, whereas no parathyroid hormone (PTH) response was observed in transgenic tumour cell lines in spite of high alkaline phosphatase activity. These data indicate that deregulated fos expression interferes with terminal osteogenic differentiation in v-fos- and c-fos-induced bone tumours.

Alkaline Phosphatase↗

The significance of retroviruses in oncology.

Retroviruses first attracted attention as the etiological agents of tumors in various animals, including birds, rodents and primates. The retrovirus-induced tumors comprise above all T- and B-cell leukemias/lymphomas, chronic myelogenous leukemia and mammary carcinomas, and are characterized by a long latent period between infection and manifestation of the disease. Since their detection, oncogenic retroviruses have been the object of intense study contributing to our knowledge of basic mechanisms and molecular events involved in carcinogenesis in general. An essential step in the retrovirus life cycle is the covalent integration of the double-stranded DNA copy of viral RNA into the cellular genome, forming the provirus. The proviruses are quite stable and are generally a permanent acquisition for the cellular genome. Therefore, the presence of the provirus can have profound genetic implications for the host cell. There are at least three main routes that are assumed to lead to retroviral oncogenesis: Transduction of cell-derived oncogenes (v-onc) carried by some retroviruses, activation of cellular proto-oncogenes (c-onc) in cis by insertional mutation or activation of cellular genes in trans by virus encoded transcription factors.

Animals↗

Ultraviolet-induced changes in corneal transmission properties and influence on Scheimpflug photography.

The effects of ultraviolet B (UV-B) irradiation on transmission of the rat cornea were studied in combination with or without naphthalene feeding. UV irradiation as well as naphthalene feeding caused a decrease in transmission in the wavelength region from 315 to 450 nm, UV irradiation being thereby the more hazardous influence. The combination of both noxae did not lead to a pronounced decrease as compared with UV irradiation alone. Although the histological findings of the eye lens suggest a syncataractogenic action of UV-B and naphthalene feeding, a corresponding effect could not be found by means of Scheimpflug photography. This could be possibly due to the alteration in corneal transmission properties following UV-B irradiation.

Animals↗

[Juxta-articular osteoid osteoma--Image morphology and diagnosis].

Juxta-articular osteoid osteomas as a cause of persistent pain of the shoulder, elbow and knee are presented basing on three own observations and a review of the literature. The sequence of the imaging examinations is equivalent to the osteoid osteomas in other localisations. CT permits a clear presentation of the nidus in the complex juxta-articular anatomy. Juxta-articular osteoid osteomas often show an absent or small perifocal osteosclerosis, whereas a laminar periosteal reaction was seen in all own cases.

Adolescent↗

No lens changes caused by simvastatin results from a prospective drug safety study.

45 patients suffering from a primary hypercholesterolemia were treated with Simvastatin. Additionally to internal visits regular ophthalmologic examinations were performed. The main interest concerning the ophthalmologic examination was directed toward the documentation and measurement of lens opacities by means of Scheimpflug photography. Moreover, every 6 months a complete regular ophthalmologic examination was carried out. We present the results after a time period of 2 years. Relevant changes in clinical findings could not be found. In some patients the Scheimpflug measurement revealed an increase in light scattering. These findings, however, were within the limit of normal age related changes.

Adult↗

Ocular drug-safety study with the HMG-CoA reductase inhibitor pravastatin.

35 pravastatin-treated patients with familial hypercholesterolemia were included in an ocular drug-safety study. Besides general examinations performed by the department of internal medicine a complete ophthalmological examination with special respect to lens opacities was carried out at the beginning, followed by control visits every six months. Scheimpflug photography of the eyes and densitometric image analysis provided objective data on lens transparency. After 18 months of treatment there is no evidence for any pathological lens changes induced by the drug applied. A decrease in visual acuity of 0.2 or more as seen in two eyes was not accompagnied by a corresponding increase in lens opacities. These observations correspond with the results of other HMG-CoA reductase inhibitors tested so far.

Anterior Eye Segment↗

Influence of nootropic drugs on the age-dependent potassium-coupling of transmitter release.

The potassium-induced dopamine release from rat striatum slices shows an age-dependent decline comparable to observations after hypoxia. Pretreatment of aged animals with antihypoxically active nootropic drugs for three weeks results in an improvement of the impaired transmitter release. Simultaneously the slope of the stimulus-release relation is increased and an age-related 50% decrease of the high affinity Ca(++)-ATPase activity (brain P2 fraction) is partially compensated. Like the antihypoxic effect, the effectiveness of nootropic drugs regarding age-dependent changes of neuronal functions probably will consist, above all, in vascular influences of the microcirculation, repair of phospholipids damaged by free radical triggered peroxidation and improvement of stimulus-release coupling.

Aging↗

Entry of the hearing impaired into the health care system.

The current system of referral of patients complaining of hearing loss usually requires a dual appointment with otolaryngology and audiology. Most of these patients have sensorineural hearing loss for which there is rarely surgical or medical treatment. This study tests the hypothesis that these patients would receive appropriate treatment and that health care dollars would be saved if an audiological assessment could identify those patients who require medical or surgical care. One hundred consecutive patients whose sole complaint was hearing loss were evaluated using audiograms and "hearing abilities questionnaires" by five audiologists using subjective and objective criteria to determine the need for referral to otolaryngology. Audiologists determined the need for referral with an accuracy of 55% and 72% utilizing subjective and objective criteria, respectively. The questionnaire was found to be of little value. Audiologists may be able to function as the entry point into the health care system for patients complaining of hearing loss. We are encouraged by the results of this preliminary study, but improvement in the system by which audiologists detect disease is necessary.

Adolescent↗

Comparative studies on the anticonvulsant effectiveness of nootropic drugs in kindled rats.

In an attempt to characterize the anticonvulsant efficacy of nootropics, their effect on different types of kindled seizures in rats has been studied. Nootropics in doses known to have protective effects in damaged brain functions possess anticonvulsant potency preferentially in pentylenetetrazole (PTZ)-kindled rats and generalized seizures. The most pronounced potency was seen in PTZ-kindled rats, where all substances tested (piracetam, meclofenoxate, pyritinol, vinpocetine, methylglucamine orotate, naftidrofuryl) led to significant dose-dependent anticonvulsant effects. In amygdala-kindled rats only vinpocetine, meclofenoxate and piracetam were effective. In neocortically kindled rats only vinpocetine and, to a smaller extent, pyritinol showed anticonvulsant effects. The data support the potential antiepileptic potency of nootropics.

Animals↗

[Assessment of the grading of cartilaginous tumors of the long tubular bones from the radiologic and pathologic viewpoint].

Based on 46 enosteal cartilaginous tumours of the long tubular bones (43 patients) the established radiological and Mirra's histopathological criteria of tumour status are assessed independently and compared retrospectively. In lesions of Lodwick's type I B (37 cases) with mineralisation of the cartilaginous matrix and facultatively cortical arrosion, lack of periosteal reaction, destruction of the corticalis and parosseal tumour extension none of Mirra's histopathological criteria of malignancy was found. It may be expected that biopsy and histopathological examination will not give valuable additional information in this radiological constellation, because there are no known definite histopathological criteria of benignity. Suspicious radiological findings should prompt complete resection of the lesion. Biopsy and histopathological classification are always crucial when matrix mineralisation is lacking and therefore the diagnosis of a cartilaginous tumour cannot be established radiologically.

Adult↗

Influence of nootropic drugs on apomorphine-induced stereotyped behaviour in rats.

In an attempt to identify the functional role of cerebral dopaminergic processes for the action of nootropic drugs the influence of piracetam, meclofenoxate, pyritinol, vinpocetine and methylglucamine orotate on apomorphine-induced stereotyped behaviour was studied. Meclofenoxate, pyritinol, vinpocetine and methylglucamine orotate enhanced significantly the apomorphine-elicited stereotypy in rats without triggering the behaviour itself. Piracetam (300, 500 or 1000 mg/kg ip.) was ineffective in this test. These results support the assumption that the functional activation of cerebral aminergic processes plays a possible role in the mode of action of some typical representatives of nootropic drugs.

Animals↗

Computer-assisted imaging cytometry of nuclear chromatin reveals bone tumor virus infection and neoplastic transformation of adherent osteoblast-like cells.

Established osteoblast-like (OB) cells infected with the bone tumor-inducing C-type retrovirus OA MuLV remained nontumorigenic over 104 cell culture passages. DNA histograms revealed a new cell population with a stem line peak at 5c. A second OA MuLV-infected OB cell line underwent neoplastic transformation with increasing passage level. These cells showed diffuse aneuploidy. Stepwise linear discriminant analysis of the chromatin structure of control, OA MuLV-infected, and FBR osteosarcoma virus-transformed cell lines resulted in various levels of discrimination ranging between 79.6% for control cells versus nontumorigenic OA MuLV-infected cells, and 96.6% for nontumorigenic OA MuLV-infected cells versus FBR osteosarcoma virus-transformed cells. OA MuLV-infected tumorigenic cells and FBR osteosarcoma virus-transformed cells were discriminated at a 93.6% level.

Animals↗

Evidence for an osteoblast-activating factor in a patient with peripheral T-cell lymphoma and osteosclerosis.

A patient with peripheral T-cell Lymphoma and acquired, systemic osteosclerosis is described. Bone histology showed a spectacular activation of osteoblasts accompanyed by massive new bone formation. Alkaline phosphatase in serum was elevated and increased to greater than 2000 U/l when the lymphoma became refractory to chemotherapy. In the patient's serum an osteoblast-activating factor could be demonstrated using a rat osteogenic osteosarcoma cell line (ROS 17/2.8). The factor was absent during remission of the tumor. We conclude that osteosclerosis was a paraneoplastic syndrome in this patient due to the secretion of an osteoblast-stimulating factor by the T-cell lymphoma. This situation is similar to the secretion of osteoclast-activating factors described in B-cell lymphomas, particularly multiple myeloma. The characterization of such a factor could be of therapeutic relevance.

Adult↗