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Biomedical subjects

H L Schmidts

Publications and source records attributed to H L Schmidts.

At least 19 recordsLinked to original sources
PubMed1999

Upregulation of the p75 but not the p55 TNF-alpha receptor mRNA after silica and bleomycin exposure and protection from lung injury in double receptor knockout mice.

We have investigated a potential role for tumor necrosis factor (TNF)-alpha and its two receptors (p55 and p75) in lung injury. We used several varieties of mice exposed endotracheally to two fibrogenic agents, silica (0.2 g/kg) and bleomycin (4 U/kg). The lungs were analyzed at 14 and 28 d after exposure to bleomycin or silica, respectively, for TNF and TNF receptor (TNFR) messenger RNA (mRNA), hydroxyproline content, and histopathology. Silica induced increased (over saline-treated animals) expression of TNF mRNA in double TNFR knockout (Ko), C57BL/6, BALB/c, and 129/J mice. In contrast, bleomycin increased expression in all but BALB/c mice, which are resistant to the fibrogenic effects of this drug. mRNA expression of both receptors was constitutively expressed in all of the normal murine strains. Silica upregulated expression of the p75 receptor, but not the p55 receptor, in the C57BL/6, BALB/c, and 129/J mice. In comparison, bleomycin had little effect on either receptor in the bleomycin-resistant BALB/c mice. Hydroxyproline content of the lungs after treatment followed this same pattern, with significant increases caused by silica in the C57BL/6, BALB/c, and 129/J mice, whereas bleomycin caused no apparent increases in the BALB/c mice. Even though silica and bleomycin induced increases in TNF in the TNFR Ko mice, the mice were protected from the fibrogenic effects of these agents. This study supports the concept that TNF is a central mediator of interstitial pulmonary fibrosis.

Animals↗
PubMed1996

ACE inhibition decreases postoperative mortality in rats with left ventricular hypertrophy and myocardial infarction.

UNLABELLED: In male Sprague Dawley rats with left ventricular hypertrophy (LVH) and hypertension induced by aortic constriction (AC) and subsequent myocardial infarction (MI) by occlusion of the left coronary artery the effects of ACE inhibition with ramipril (RA 1 mg/kg/day via the drinking water during 6 weeks) on survival as well as cardiac function and metabolism were investigated. Respective groups (sham AC; AC; AC + sham MI; normotensive animals with sham MI; MI; MI + RA) served as comparisons. Following MI hypertensive rats with AC and LVH revealed an increased postoperative mortality (68%) when compared to normotensives without AC (28%). ACE inhibition with ramipril significantly reduced mortality in hypertensive rats by 26%. Untreated hypertensive animals with LVH clearly showed reduced MI size (6.2 +/- 2.3%) in comparison with untreated normotensive animals and MI (31.0 +/- 3.3%). In hypertensive rats with MI which died during the study a significant increase in infarct size was found compared to those which survived MI. In normotensive animals ramipril reduced infarct size by 50%. Due to the quite small infarct size observed in hypertensive rats, ACE inhibition did not further reduce MI in these animals. LVH as well as hydroxyproline/proline ratio was diminished by ACE inhibitor treatment. In the isolated hearts of ramipril treated rats contractility was improved when compared to the respective untreated groups with MI. In the coronary effluent of isolated hearts from rats with AC and MI lactate dehydrogenase and creatine kinase activities as well as lactate levels were increased. Ramipril treatment starting one week before MI normalized these parameters and in addition increased prostacyclin output. Hearts with MI from treated normotensive animals contained increased energy rich phosphates when compared to hearts from untreated rats with MI. CONCLUSIONS: Hypertensive rats with LVH undergoing MI experience increased postoperative mortality probably due to a reduced tolerance to myocardial ischemia and occurrence of arrhythmias. In these animals ACE inhibition with ramipril increased survival. Both, increased survival in hypertensive and reduction in infarct size in normotensive rats by ACE inhibition with ramipril was accompanied by an improved myocardial metabolism.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Comparative efficacies of ofloxacin, cefotaxime, and doxycycline for treatment of experimental epididymitis due to Escherichia coli in rats.

The in vivo efficacy of ofloxacin was compared with those of cefotaxime and doxycycline in a rat model of epididymitis due to Escherichia coli. Treatment was started 24 h after infection and was continued for 7 days. Ofloxacin reduced the numbers of E. coli organisms in the epididymides significantly more than the other therapeutic regimens and cured the infection more frequently. Histopathological changes in the epididymides of ofloxacin-treated animals were significantly less severe than those observed in untreated animals. Doxycycline was less effective than ofloxacin but significantly reduced the titers of organisms in rat epididymides. In contrast, despite excellent in vitro activity, cefotaxime failed to reduce the magnitude of infection. The results of this study suggest that ofloxacin may be a very effective antimicrobial agent for the treatment of epididymitis due to E. coli.

Animals↗
PubMed1991

Beneficial effects of inhibitors of prolyl 4-hydroxylase in CCl4-induced fibrosis of the liver in rats.

S 0885 and HOE 077 inhibit CCl4-induced liver fibrosis in rats, as shown by significantly reduced hydroxyproline content of the liver and improved liver histology. Mortality of drug-treated animals is significantly diminished. Serum collagen parameters correlate well with the hydroxyproline content of the liver and can be used as noninvasive markers for the fibrotic process. HOE 077 is a proinhibitor, which by itself does not inhibit prolyl 4-hydroxylase. HOE 077 is well absorbed from the gastrointestinal tract. It is taken up by rat liver and is converted to the active metabolites. At a concentration of 1 mM, HOE 077 does not affect collagen synthesis in human fibroblasts, bovine chondrocytes and chicken calvaria. At therapeutic doses the compound does not reduce collagen content of kidney, lung, aorta, femur epiphysis, skin and tendon of the rat, validating the high specifity of the liver selective prodrug/inhibitor conversion. From animal experiments, a human daily dose of 0.5-1 g can be extrapolated.

Animals↗
PubMed1991

Immuno- and enzymehistochemical characterization of 'plasmacytoid T-cells' in formalin-fixed paraffin-embedded tissue of reactive lymph nodes.

In eight (10.4%) of 77 randomly selected cases of lymphadenitis, foci of 'plasmacytoid T-cells' (PTCs) were found. We characterized the PTCs in formalin-fixed paraffin-embedded tissue by immuno- and enzymehistochemical techniques. In each case the PTCs formed nodular and patchy infiltration patterns around the high endothelial venules in the paracortex of the lymph nodes. The PTCs in half of the cases were present near the intermediary peritrabecular sinuses. The PTCs were found to be positive for CD 45 (LCA), CD 45 R (4 KB 5) and CD 43 (MT 1), but not for CD 45 RO (UCHL 1), L 26 (CD 20), myeloperoxidase, naphthol AS-D chloroacetate esterase, Mac 387, alpha-1-antichymotrypsin or S 100 protein and anti-dendritic reticulum cell antibody. Some lysozyme+ PTCs were mingled in and around the foci in each case. In five cases the PTCs showed weaker positive reactions for CD 68 (EBM 11) and HLA-DR than for T-zone macrophages and sinus histiocytes. Related to the degree of desintegration of the nodular PTC-foci increasing numbers of T- and B-lymphocytes, T-zone macrophages and interdigitating reticulum cells with HLA-DR were detected in the foci. In two cases, where there was no HLA-DR expression by PTCs, small amounts of HLA-DR in secondary lymph follicles and a decrease of HLA-DR+ T-zone macrophages and interdigitating reticulum cells were observed. Our results suggest that there is a high degree of interaction between PTCs and other cellular components in the lymph node. The PTC may represent a special type of resident macrophage with secretory capacities.

Adult↗
PubMed1987

Autopsy findings in AIDS--a histopathological analysis of fifty cases.

Fifty consecutive AIDS autopsy cases were evaluated. All subjects showed one or more opportunistic infections and malignancies included in the AIDS case definition with cytomegalovirus and Kaposi's sarcoma being most prevalent. Mycobacterial and cryptococcal infections occurred only infrequently. Most patients of our series after successful treatment of Pneumocystis carinii pneumonia or cerebral toxoplasmosis later succumbed to less treatable conditions like disseminated cytomegalovirus or fungal infections or malignant lymphoma. In the absence of specific treatment for the HIV infection leading to these lethal complications special emphasis must be put on the prevention of HIV transmission and spread.

Acquired Immunodeficiency Syndrome↗
PubMed1987

In situ hybridization analysis of cytomegalovirus lytic infection in Kaposi's sarcoma associated with AIDS. A study of 14 autopsy cases.

Cytomegalovirus (CMV) was assayed by in situ hybridization with commercially available biotin-labeled CMV-DNA probes in 45 formalin-fixed paraffin-embedded autopsy specimens with Kaposi's sarcoma from 14 cases of the acquired immune deficiency syndrome (AIDS). In seven of the 14 cases, a few scattered hybridizing cells were detected in Kaposi's sarcoma, but not all specimens from the same case showed such cells. Most of the positive cells were peculiarly swollen and not typical of Kaposi's sarcoma cells. All positive cases had at least some CMV-infected organs with typical cytomegalic cells containing nuclear inclusions while five of the 7 negative cases revealed no CMV-infected tissue by conventional light microscopy. Our results suggest that this in situ hybridization procedure using biotin-labeled DNA probes only reveals generalized CMV infection that is a consequence of impairment of immune mechanisms in AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1987

[Pathogenesis, clinical aspects, morphology, therapy and prognosis of phyllodes tumors of the breast].

A case is reported of a malignant cystosarcoma phylloides. After 7-year-follow-up period an increase in size was observed in a mammary nodule, first suspected diagnostic ascertainment. Histology of the removed tumor with an unsuspicious tissue sheath revealed a malignant cystosarcoma. Consequently, any palpable breast node suspected to be fibroadenoma should be removed with short-spaced follow-up examination or at least observed over long periods of time in view of the possible malignant degeneration despite of absent criteria of malignancy.

Biopsy, Needle↗
PubMed1984

[Behavior of atheromatous vessel segments during pressure application of 5 kg/cm2 for various periods of time].

In this study changes in weight and thickness of atheromatous vessel wall segments in relation to a varying duration (2-60 sec.) of a constant pressure application (5 kg/cm2) were investigated. Vessel wall segments were taken shortly postmortem from human femoral and external iliacal arteries. According to the type of atherosclerotic changes the samples were divided into 2 types (lipoidosis/sclerosis) before the experiments. As standard served non-atheromatous segments. During pressure application all specimens showed rapid decrease in weight and thickness within the first 40 seconds. After 50 seconds no further change could be seen. Atheromata predominantly containing lipids and few collagen fibres showed higher decrease in weight and thickness than those predominantly containing collagen and the control group. A positive correlation was shown between decrease in weight and thickness of the specimens. Is is concluded that squeezing out tissue fluid by pressure application may lead to a decrease in thickness of the atheromata; the enlargement of the luminal diameter achieved by balloon catheters may be attributed to this mechanism.

Angioplasty, Balloon↗
PubMedDate not supplied

In situ immunophenotyping of lymphocytes/macrophages: grading of lymphadenopathy, staging and pathophysiology of HIV infection.

Histological changes in lymph nodes in HIV1-related lymphadenopathy were analysed in 106 lymph node biopsies and in lymph nodes of 140 autopsy cases. A classification system of five stages was established on the basis of histological and immunohistochemical studies. The analysis confirmed a close correlation between the progression of HIV1-related disease and our staging system. Although the classification is chiefly based on histological and immunohistochemical changes of the follicles, other frequently seen findings are included. Alterations in the interfollicular tissue, e.g. vascular proliferation and lymphocyte depletion, correspond to an increasing concentration of macrophages within this tissue. In HIV1 infection, the macrophages appear to produce high concentrations of angiogenic factors responsible for the frequent and sometimes extreme lymph node vascularization. Since the vascular proliferation can be subject to regression and sclerosis as seen in autopsy cases, the macrophages may lose the ability to produce large amounts of angiogenic factors in the final stage of the disease.

AIDS-Related Complex↗
PubMedDate not supplied

Pathophysiological mechanisms of HIV-induced defects in haematopoiesis: pathology of the bone marrow.

Bone marrow biopsies of 96 HIV1-infected patients were analysed histologically and by immuno- and enzyme histochemical techniques. Independently of the stage of disease, the bone marrow frequently exhibits hypercellularity and features of dysplastic haemopoiesis combined with mesenchymal alterations. In situ immunohistochemical analysis shows that there is a marked reduction in expression of the proliferation-associated nuclear antigen recognized by the Ki67 antibody. Comparison with non-infected controls reveals that there is a reduction in CD34+/myeloperoxidase-/naphthol AS-D chloroacetate- progenitor cells and an overproportional decrease in CD8+ lymphocytes in the bone marrow. Double staining revealed the presence of gag-coded HIV1 proteins in the above-mentioned CD34+ progenitor cells, in myelopoiesis cells, megakaryocytes and above all, in CD68+/acid phosphatase+ and alkaline phosphatase+ bone marrow reticular cells. From the latter results, it was concluded that HIV1-infected reticular cells may be disturbed in their ability to produce factors responsible for the short-range regulation of haemopoietic activity.

Acquired Immunodeficiency Syndrome↗