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Biomedical subjects

M Grob

Publications and source records attributed to M Grob.

At least 19 recordsLinked to original sources
PubMed2005

[Balloon dilatation and Stentimplantation of the nasolacrimal duct for chronic epiphora].

PURPOSE: To examine the clinical outcome of the ballon dilatation in stenosis and obstruction of the nasolacrimal duct. MATERIAL AND METHODS: 63 patients (69 nasolacrimal duct systems) with epiphora and proven obstruction of the nasolacrimal duct were treated with ballon dilatation, respectively Stentimplantation. In 55 cases there was a pre- or postsaccal stenosis, in 14 cases an occlusion of the nasolacrimal duct system. The diagnosis was established by dacryocystography. RESULTS: Technical success was obtained in 61 cases (n=50/55 stenosis; n=11/14 occlusions). Over a mean follow-up of 6 months patency of the nasolacrimal duct system was achieved in 83,6% (46/55) in stenosis. In occlusion the clinical outcome was 42,9% (6/14). CONCLUSION: Balloon dacryocystoplasty and Stentimplantation are minimal-invasive alternatives, performed in local anesthesia that recover the normal anatomy of the nasolacrimal duct system. They are a good alternative in the treatment of epiphora caused by nasolacrimal duct obstructions.

Adult↗
PubMed2003

Characterization of the neurochemical content of neuronal populations of the lamina terminalis activated by acute hydromineral challenge.

The lamina terminalis (LT) contains three main regions, namely the subfornical organ (SFO), the median preoptic nucleus (MnPO) and the vascular organ of the LT (OVLT). Although LT is recognized of paramount importance in the regulation of hydromineral homeostasis, identity of the neurocircuits interconnecting the SFO and OVLT to the MnPO is not known. Furthermore, the phenotype of neuronal populations activated during acute hydromineral challenge is not yet determined. By using the high cellular resolution of the in situ hybridization histochemistry (ISHH), we investigated whether a furosemide-induced fluid and electrolyte depletion might modify both putative GABAergic and glutamatergic systems within the LT. We show that acute furosemide treatment (4 h) significantly reduced the expression of GAD67 mRNA, the active holoenzyme predictive of GABA synthesis, within the SFO. A strong tendency toward a reduction of GAD67 signal was also observed in the OVLT and MnPO. The hydromineral challenge did not alter the expression of GAD65 and type 2 vesicular glutamate transporter (vGlut2) mRNA in all the structures of the LT. Furosemide treatment was associated with a reduction in the population of GAD67-containing neurons in the periphery of the SFO and dorsal part of the MnPO. Contrastingly, GAD65-containing cells were shown to be increased in the OVLT and no change was observed for the vGlut2-containing neurons in the whole LT. By combining ISHH with immunohistochemistry (Fos immunoreactivity), we report that furosemide-induced water and sodium depletion did essentially recruit a glutamatergic network throughout the LT, although GABAergic neurons were specifically activated in the ring of the SFO and in the OVLT. The MnPO, the region of the LT that is considered as being an integrative area for sensory inputs arising from the SFO and OVLT, showed exclusive activation of excitatory neuronal populations. Taken together these results suggest that acute water and Na(+) depletion diminish the efficacy of the GABAergic system and mainly activates excitatory neuronal pathways in the regions of the LT.

Animals↗
PubMed2003

Altered intracellular expression of the chemokines MIP-1alpha, MIP-1beta and IL-8 by peripheral blood CD4+ and CD8+ T cells in mild allergic asthma.

BACKGROUND: The ability of chemokines to regulate Th1 and Th2 responses suggests a role in the pathogenesis of atopic disorders such as allergic asthma where Th2 response dominance has been observed. Although the impact of allergic asthma on local chemokine production in the lung has been the subject of investigation, little is know about the influence of disease progression on peripheral chemokine production. We now report use of whole blood culture and flow cytometry to assess the influence of mild allergic asthma on peripheral T-cell chemokine expression. METHODS: Study participants included patients with mild allergic asthma (n = 7) and nonasthmatic controls (n = 7). Following in vitro stimulation of peripheral venous blood with phorbol 12-myristate acetate (PMA) and ionomycin, flow cytometry was used to estimate the percentage of CD4+ and CD8+ T cells producing a number of chemokines, including macrophage inflammatory proteins MIP-1alpha and MIP-1beta, RANTES (regulated on activation, T-cell expressed and secreted), monocytic chemotactic protein-1 (MCP)-1, and interleukin (IL)-8, or the cytokines interferon (IFN)-gamma and IL-4. Serum levels of MIP-1alpha, MIP-1beta, RANTES, MCP-1, IL-8, IFN-gamma and IL-4 were also assessed by quantitative ELISA. RESULTS: Intracellular expression of MIP-1beta by CD4+ and CD8+ T cells from allergic asthmatics was significantly reduced in comparison to that observed for nonasthmatics (median = 2.29% (1.75-3.50) vs 4.57% (3.38-6.64), P = 0.05; 14.20% (13.18-17.88) vs 44.10% (30.38-48.70), P = 0.01). Similarly, intracellular expression of MIP-1alpha by CD8+ T cells from allergic asthmatics was also significantly lower (3.67% (1.17-5.42) vs 17.10% (4.97-20.43), P = 0.05). Conversely, IL-8 expression by both CD4+ and CD8+ T cells from allergic asthmatics demonstrated significant enhancement (9.93% (7.77-11.28) vs 4.14% (3.61-7.11), P = 0.05; 8.40% (6.97-10.04) vs 4.98% (3.37-6.08), P = 0.05). Examination of intracellular IFN-gamma and IL-4 revealed no significant difference in the expression of either cytokine by CD4+ T-cells from allergic asthmatics and nonasthmatics. In contrast, expression of IFN-gamma was significantly reduced in CD8+ T-cells from allergic asthmatics (24.60% (21.08-32.50) vs 48.40% (41.50-55.28), P = 0.01). CONCLUSIONS: The occurrence in mild allergic asthma of peripheral T-cell chemokine expression suggestive of a diminished Th1 response, coinciding with marginal change in cytokine profiles indicative of a Th2 response bias, confirms the importance of chemokine involvement in the etiology of allergic asthma. The ability to use whole blood culture to estimate chemokine expression in T cell subsets may ultimately provide a practical means to evaluate disease status and to monitor early intervention therapies which target chemokines.

Adult↗
PubMed2001

Distinct sites of origin of oligodendrocytes and somatic motoneurons in the chick spinal cord: oligodendrocytes arise from Nkx2.2-expressing progenitors by a Shh-dependent mechanism.

In the vertebrate spinal cord, oligodendrocytes arise from the ventral part of the neuroepithelium, a region also known to generate somatic motoneurons. The emergence of oligodendrocytes, like that of motoneurons, depends on an inductive signal mediated by Sonic hedgehog. We have defined the precise timing of oligodendrocyte progenitor specification in the cervico-brachial spinal cord of the chick embryo. We show that ventral neuroepithelial explants, isolated at various development stages, are unable to generate oligodendrocytes in culture until E5 but become able to do so in an autonomous way from E5.5. This indicates that the induction of oligodendrocyte precursors is a late event that occurs between E5 and E5.5, precisely at the time when the ventral neuroepithelium stops producing somatic motoneurons. Analysis of the spatial restriction of oligodendrocyte progenitors, evidenced by their expression of O4 or PDGFR(&agr;), indicate that they always lie within the most ventral Nkx2.2-expressing domain of the neuroepithelium, and not in the adjacent domain characterized by Pax6 expression from which somatic motoneurons emerge. We then confirm that Shh is necessary between E5 and E5.5 to specify oligodendrocyte precursors but is no longer required beyond this stage to maintain ongoing oligodendrocyte production. Furthermore, Shh is sufficient to induce oligodendrocyte formation from ventral neuroepithelial explants dissected at E5. Newly induced oligodendrocytes expressed Nkx2.2 but not Pax6, correlating with the in vivo observation. Altogether, our results show that, in the chick spinal cord, oligodendrocytes originate from Nkx2.2-expressing progenitors.

Animals↗
PubMed2000

Mental stress increases right heart afterload in severe pulmonary hypertension.

Little is known about mental stress effects on the pulmonary circulation in health and disease. The current study was conducted to investigate whether pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) would further increase during standardized mental stress testing in patients with severe pulmonary hypertension. The study was a prospective analysis of seven patients (average age: 40 years, range from 21 to 56 years) with severe pulmonary hypertension (primary: n = 4, secondary forms: n = 3; resting mean pulmonary artery pressure ranged between 48 and 65 mmHg). Right heart catheterization for the determination of PAP, pulmonary capillary wedge pressure (PCW) and cardiac output (CO) was clinically indicated (diagnostic workup, acute drug testing). Patients accomplished a standardized 10 min mental stress test (computer based, adaptive complex reaction-time task). Pulmonary haemodynamics during stress were compared to resting baseline. During mental stress mean PAP (+/- SEM) increased by 9.4 +/- 2.1 mmHg (P < 0.005). Pulmonary vascular resistance increased by 149 +/- 25 dyne s cm-5 (P < 0.001). Stroke volume decreased by 6.6 +/- 2.2 ml (P < 0.03). The data show that moderate mental stress increases right heart afterload in patients with severe pulmonary hypertension owing to elevation of PVR.

Adult↗
PubMed1999

[Delay of the diagnosis of an amelanotic malignant melanoma due to CO2-laser treatment--case report and discussion].

The incidence of malignant melanoma is steadily increasing. The best prognostic indicator of melanoma is the vertical tumor thickness. Early recognition of melanoma by the naked eye is often difficult, because many lesions simulate its clinical presentation. We report on a 47-year-old man with a red papular skin lesion treated by CO2 laser. The histological diagnosis of an amelanotic malignant melanoma was thus delayed for one year. Clinically ambiguous skin tumors should never be treated by laser prior to a diagnostic biopsy.

Carbon Dioxide↗
PubMed1998

[Grain mites. A small epidemic caused by Pyemotes species].

Pyemotes mites, of which the grain itch mite is the most important for human medicine, are ectoparasites of many insect species. Human infestation occurs only accidentally and temporally. The source materials are most often grain, straw and plant-based foods. Bites produce an intensely itching urticarial wheal capped by pin-point vesicles, which often are destroyed by scratching. Pyemotes dermatitis favours the back, the abdomen and the flexor side of the forearms. The mites are barely visible to the naked eye and reside only briefly on humans and thus are not found by physicians during clinical examination. When itching starts, the parasites have usually left their hosts. Therefore it is important to investigate the patient's environment and to identify the infested materials. We describe an outbreak of Pyemotes dermatitis in at least 16 persons, most of them warehouse workers in a hobby mail-order house. Infested decorative wheat was the source of the problem. Successful eradication was achieved by fumigation of the storage facilities with the insecticide methylbromide. Our cases demonstrate the importance of examination of environmental specimens for ectoparasites in cases of unexplained dermatoses. Biological agriculture avoiding insecticides may cause reappearance of this almost forgotten skin disease.

Adult↗
PubMed1998

Histopathologic and ultrastructural study of lupus-like skin lesions in a patient with Bloom syndrome.

The histopathology of the lupus-like skin lesions associated with Bloom syndrome has been sporadically described. Skin biopsies from a 2-year-old boy with the classical features of Bloom syndrome, including lupus-like skin lesions, demonstrated marked interface changes with basal liquefaction degeneration, a moderate superficial mononuclear infiltrate, pigmentary incontinence, and capillary dilation in the papillary dermis. Immunophenotyping of the dermal infiltrate revealed predominance of T-cells. Basement membrane thickening on periodic acid-Schiff examination was not seen. Direct immunofluorescence failed to demonstrate deposits of immunoglobulin other than nonspecific IgM deposition along the basement membrane zone of lesional skin. Ultrastructurally, the most striking findings were disintegration of basal cell cytoplasm and tubuloreticular inclusions in vascular endothelia. Taken together, the histologic and ultrastructural features of lupus-like lesions associated with Bloom syndrome mimic those of cutaneous lupus erythematosus, with the exception of paucity of immune deposits at the dermoepidermal junction.

Basement Membrane↗
PubMed1998

Recruitment of the LIM protein hic-5 to focal contacts of human platelets.

Platelets are anuclear, membrane-bounded fragments derived from megakaryocytes which, upon stimulation, assemble an actin skeleton including stress fibres and focal contacts. The focal contacts resemble those of tissue culture cells. However, they lack paxillin, a conspicuous component of these organelles. We found that instead of paxillin, platelets contain a related protein with a molecular mass of 55 kDa that crossreacts with a monoclonal antibody against paxillin. The gene for the 55 kDa protein was cloned from a bone marrow cDNA library and turned out to be identical to a recently discovered gene encoding hic-5. Like paxillin, hic-5 is a cytoskeletal protein containing four carboxy-terminal LIM domains and LD motifs in the amino-terminal half. The LIM domains of both hic-5 and paxillin are capable of targetting green fluorescent protein to focal contacts. In addition, GST-hic-5 precipitates the focal adhesion kinase pp125(FAK) and talin from platelet extracts. Only trace amounts of hic-5 occur in DAMI cells, a megakaryocytic cell line, and in megakaryocytes cultured from CD34+ cells obtained from umbilical cord blood. However, RT-polymerase chain reactions performed with RNA obtained from platelets gave a positive result when primers specific for hic-5 were used, but were negative with paxillin-specific primers, indicating that a switch from paxillin expression to hic-5 expression must occur late in the maturation of megakaryocytes into platelets.

3T3 Cells↗
PubMed1998

[Topical photodynamic therapy in dermatology].

Photodynamic therapy (PDT) is an experimental, noninvasive treatment of different malignant tumors. The principle is that applied photosensitizing substance selectively accumulate in neoplastic cells. Exposure to visible light then leads to the destruction of the tumor tissue. Following intravenous or oral administration of the photosensitizer (PS) generalised skin photosensitivity is the major side effect. Topical application of the PS under occlusive foil a novel method. Topical PDT (TPDT) is most investigated with 5-Aminolevulinic acid (ALA) as PS. ALA is a precursor of endogenous porphyrins in the biosynthetic pathway for heme. This new modality is increasingly and successfully used to treat precancerous and cancerous epithelial skin tumors, like actinic keratoses, basal-cell carcinoma, squamous-cell carcinoma and Bowen disease. An other approach of ALA-TPDT are nontumoral applications, especially psoriasis. ALA-TPDT is well tolerated by patients and makes excellent cosmetic results. It is an alternative treatment for various superficial skin tumors.

Aminolevulinic Acid↗
PubMed1997

Prostate-specific membrane antigen and other prostatic tumor markers on the horizon.

The PSM antigen is an exciting new molecule with many potentially valuable applications. Further research with PSM may help us to elucidate the complex process of prostatic neoplasia better. Current avenues of research with PSM include the generation of new and improved monoclonal antibodies targeting different portions of PSM and PSM', which may improve the results of imaging and targeting prostate cancer. Gene therapy using the PSM promoter to drive prostate-specific expression of various cytokines and other factors is another exciting potential application deserving of attention, and refinement of serum PSM assays may greatly add to the present array of diagnostic modalities offered to patients with suspected prostate cancer. Thus, PSM is a potentially valuable addition to our armamentarium of prostate markers. Additionally, a host of other potential markers to increase our understanding of the complex biology of the normal and malignant prostate are on the horizon. Just how far away that horizon is awaits further basic and clinical investigations.

Antigens, Neoplasm↗
PubMed1997

Human bone cells stimulate the growth of human breast carcinoma cells.

Human breast cancer cells were cultured together with their metastatic target, bone tissue, to analyze possible growth promotion effects. The coculture of human osteosarcoma cells (TE-85) with human mammary carcinoma cells (ZR-75.1) resulted in up to 8.4-fold stimulation of proliferation of the breast tumor cells. Cell contact of the two cultures was permitted through the channels of Nuclepore filters. However, physical contact turned out not to be necessary, since the proliferative stimulus was also mediated by a bone-derived diffusible factor. Conditioned medium (CM), collected from human primary bone cultures, enhanced the rate of proliferation of several breast tissue cell lines (ZR-75.1, BT-20, HBL-100), while some lines were not affected by osteoblast CM. Breast tissue lines responding to bone CM express low to intermediate levels of the c-erbB-2 gene, in contrast to nonstimulated lines, which overexpress the gene. Recent observations of metastatic spread in breast cancer patients suggest a distinctive pattern of secondary tumor distribution in association with c-erbB-2 protein expression. Bone tissue seems to be a preferential target for metastases of c-erbB-2-negative breast tumors.

Adolescent↗
PubMed1996

Prevalence of antibodies to feline parvovirus, calicivirus, herpesvirus, coronavirus, and immunodeficiency virus and of feline leukemia virus antigen and the interrelationship of these viral infections in free-ranging lions in east Africa.

While viral infections and their impact are well studied in domestic cats, only limited information is available on their occurrence in free-ranging lions. The goals of the present study were (i) to investigate the prevalence of antibodies to feline calicivirus (FCV), herpesvirus (FHV), coronavirus (FCoV), parvovirus (FPV), and immunodeficiency virus (FIV) and of feline leukemia virus (FeLV) antigen in 311 serum samples collected between 1984 and 1991 from lions inhabiting Tanzania's national parks and (ii) to evaluate the possible biological importance and the interrelationship of these viral infections. Antibodies to FCV, never reported previously in free-ranging lions, were detected in 70% of the sera. In addition, a much higher prevalence of antibodies to FCoV (57%) was found than was previously reported in Etosha National Park and Kruger National Park. Titers ranged from 25 to 400. FeLV antigen was not detectable in any of the serum samples. FCoV, FCV, FHV, and FIV were endemic in the Serengeti, while a transient elevation of FPV titers pointed to an outbreak of FPV infection between 1985 and 1987. Antibody titers to FPV and FCV were highly prevalent in the Serengeti (FPV, 75%; FCV, 67%) but not in Ngorongoro Crater (FPV, 27%; FCV, 2%). These differences could be explained by the different habitats and biological histories of the two populations and by the well-documented absence of immigration of lions from the Serengeti plains into Ngorongoro Crater after 1965. These observations indicate that, although the pathological potential of these viral infections seemed not to be very high in free-ranging lions, relocation of seropositive animals by humans to seronegative lion populations must be considered very carefully.

Africa, Eastern↗