Biomedical subjects

T Klein

Publications and source records attributed to T Klein.

At least 91 records · Page 5Linked to original sources

PubMed1999

The outcomes of an inpatient treatment program for geriatric patients with dementia and dysfunctional behaviors.

This study evaluated outcomes of an inpatient program designed to reduce severe agitated behavior in geriatric patients with dementia who could not be successfully treated on an outpatient basis. An individualized treatment plan was created for each patient (N = 250) that involved pharmacological and nonpharmacological interventions with behavioral, environmental, and psychological components. Assessment of behavioral, cognitive, and functional status was conducted for each patient on admission to the program and at discharge. Significant improvements on these assessments were observed. We conclude that the longitudinal, multidisciplinary approach used in this study was effective in significantly reducing intrusive and dangerous behaviors while preserving or enhancing patients' cognitive and functional abilities.

Aged↗

PubMed1999

Atopic dermatitis and HTLV-1-associated myelopathy: associated or coincidental disorders?

Reports from Jamaica have indicated that some patients with infective dermatitis or atopic dermatitis (AD) are seropositive for antibodies to human T-lymphotropic virus type 1 (HTLV-1). We describe a 32-year-old Israeli woman with long-term AD and paresthesia in the distal parts of the extremities. Neurological examination revealed a positive Babinski's sign. HLA typing demonstrated that this patient has the common HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and infective dermatitis haplotype for DRB1* DQB1*. The presence of HTLV-1 was demonstrated with polymerase chain reaction; HTLV-1-antibodies were detected by the Western blot method and by inoculation of the patient's peripheral blood mononuclear cells into F344 rats. This study confirms the presence of HTLV-1 antibodies and proviral genome in a patient with AD which later evolved into HAM/TSP. We cannot yet conclude whether these two diseases are associated or coincidental disorders.

Adult↗

PubMed1999

Composite signalling from Serrate and Delta establishes leg segments in Drosophila through Notch.

The receptor protein NOTCH and its ligands SERRATE and DELTA are involved in many developmental processes in invertebrates and vertebrates alike. Here we show that the expression of the Serrate and Delta genes patterns the segments of the leg in Drosophila by a combination of their signalling activities. Coincident stripes of Serrate and Delta expressing cells activate Enhancer of split expression in adjacent cells through Notch signalling. These cells form a patterning boundary from which a putative secondary signal leads to the development of leg joints. Elsewhere in the tarsal segments, signalling by DELTA and NOTCH is necessary for the development of non-joint parts of the leg. We propose that these two effects result from different thresholds of NOTCH activation, which are translated into different downstream gene expression effects. We propose a general mechanism for creation of boundaries by Notch signalling.

Adaptor Proteins, Signal Transducing↗

PubMed1999

The vestigial gene product provides a molecular context for the interpretation of signals during the development of the wing in Drosophila.

The vestigial (vg) gene of Drosophila plays a central role in the development and patterning of the wing: loss of vestigial results in failures in wing development and ectopic expression of vestigial leads to the development of ectopic wings. The wing-specific regulation of vestigial is mediated through two enhancers: (1) the Boundary Enhancer (vgBE) is early acting and becomes restricted to the wing margin, and (2) the Quadrant Enhancer (vgQE), acts later and is responsible for the expression of vestigial in the developing wing blade. These enhancers receive regulatory inputs from three signalling pathways: wingless, decapentaplegic and Notch/Suppressor of Hairless. Our experiments show that the vestigial gene product is also an input in the regulation of vestigial expression. In particular, Vestigial provides an important input for the regulation of the activity of the vgQE acting in concert with Wingless and Decapentaplegic. Our results suggest how interactions between vgBE and the vgQE mediated by Vestigial can explain the interactions between the wing margin and the wing blade during the growth of the wing. We further show that Vestigial and Notch collaborate with Wingless to subdivide and pattern the wing blade. These results lead us to propose a general role for Wingless during development in which it stabilizes cell fate decisions that have been implemented by other molecules.

Animals↗

PubMed1999

Immunolocalization of the four prostaglandin E2 receptor proteins EP1, EP2, EP3, and EP4 in human kidney.

Four prostaglandin E2 receptor subtypes designated EP1, EP2, EP3, and EP4 have been shown to mediate a variety of effects of prostaglandin E2 (PGE2) on glomerular hemodynamics, tubular salt and water reabsorption, and on blood vessels in the human kidney. Despite the important role of renal PGE2, the localization of PGE2 receptor proteins in the human kidney is unknown. The present study used antipeptide antibodies to the EP1 to EP4 receptor proteins for immunolocalization in human kidney tissue. Immunoblot studies using these antibodies demonstrated distinct bands in membrane fraction from human kidney. By means of immunohistochemistry, expression of the human EP1 receptor subtype protein in renal tissue was detected mainly in connecting segments, cortical and medullary collecting ducts, and in the media of arteries and afferent and efferent arterioles. The human EP2 receptor subtype protein was detectable only in the media of arteries and arterioles. The human EP3 receptor subtype protein was strongly expressed in glomeruli, Tamm-Horsfall negative late distal convoluted tubules, connecting segments, cortical and medullary collecting ducts, as well as in the media and the endothelial cells of arteries and arterioles. Staining of the human EP4 receptor subtype protein was observed in glomeruli and in the media of arteries. However, no signal of either receptor subtype was detected in the thick ascending limb, the macula densa, or in adjacent juxtaglomerular cells. These results support the concept that PGE2 modulates specific functions in different anatomical structures of the human kidney.

Amino Acid Sequence↗

PubMed1999

[Active life expectancy in Germany].

Using the method of multistate life-tables, the article presents results on active life expectancy on the basis of the German Socio-Economic Panel Survey (SOEP). Different determinants of mortality and morbidity are revealed by event-history analysis. Results show that men live a greater proportion of their lives without disability than do women. Results on the association between mortality/morbidity and socio-economic factors suggest that studies which usually focussed either on mortality or on morbidity cannot fully explain differences in active life expectancy.

Adult↗

PubMed1998

Interleukin 1beta decreases prostacyclin synthase activity in rat mesangial cells via endogenous peroxynitrite formation.

We have reported that peroxynitrite (PON) selectively inactivated prostacyclin synthase (PGIS) by a mechanism of tyrosine nitration at the active site [Zou, Martin and Ullrich (1997) Biol. Chem. Hoppe-Seyler 378, 707-713]. We have now extended our studies on rat mesangial cells (RMC) and show that nitration can occur under the influence of cytokines. Pretreatment of RMC with interleukin 1beta (IL-1beta), which up-regulated cyclo-oxygenase 2 and inducible nitric oxide synthase (NOS-2), significantly attenuated the conversion of [14C]prostaglandin H2 (PGH2) into the stable prostacyclin (PGI2) metabolite 6-oxo-prostaglandin F1alpha (6-oxo-PGF1alpha). The presence of superoxide dismutase (SOD, 100 units/ml) or the NOS synthase inhibitor Nomega-monomethyl-l-arginine (100 microM) as well as cycloheximide (10 microM) plus actinomycin (10 microM) abolished IL-1beta-mediated down-regulation of 6-oxo-PGF1alpha from PGH2. At the same time, 6-oxo-PGF1alpha production from arachidonate (AA) increased at the expense of prostaglandin E2 (PGE2). Neither NO alone generated from different NO donors nor superoxide from xanthine/xanthine oxidase (1-100 m-units/ml) inhibited PGI2 synthesis, either from PGH2 or from AA. Bolus additions of chemically synthesized PON or the PON generator 3-morpholinosydnonimine N-ethylcarbamide (SIN-1) exhibited a potent inhibition of 6-oxo-PGF1alpha release from both PGH2 and AA. In addition, immunoprecipitation of nitrotyrosine-containing proteins from PON- and SIN-1-treated RMC yielded distinct nitrated PGIS bands but also from IL-1beta-pretreated cells alone, compared with a lack of nitrated PGIS in control cells. Taken together, our results strongly suggest that IL-1beta pretreatment of RMC via NOS-2 leads to the production of PON with the consequence of a partial nitration and inhibition of PGIS.

Animals↗

PubMed1998

Localization of cyclooxygenase-2 and prostaglandin E2 receptor EP3 in the rat lumbar spinal cord.

Cyclooxygenase-2 (COX-2) is now considered to be the major constitutively expressed COX isozyme in the central nervous system. The present immunocytochemical study details localization of COX-2 immunoreactivity in rat spinal cord along with the expression of prostaglandin E2 receptor subtype EP3. Prominent COX-2 staining was observed in the nuclear envelope of neurons throughout the spinal cord, especially in the superficial dorsal horn laminae and motoneurons of lamina IX, as well as in glial cells of the white matter. Expression of EP3 receptor was strictly confined to afferent terminal areas in the superficial dorsal horns.

Animals↗

PubMed1998

CD4 T cell tolerance to human C-reactive protein, an inducible serum protein, is mediated by medullary thymic epithelium.

Inducible serum proteins whose concentrations oscillate between nontolerogenic and tolerogenic levels pose a particular challenge to the maintenance of self-tolerance. Temporal restrictions of intrathymic antigen supply should prevent continuous central tolerization of T cells, in analogy to the spatial limitation imposed by tissue-restricted antigen expression. Major acute-phase proteins such as human C-reactive protein (hCRP) are typical examples for such inducible self-antigens. The circulating concentration of hCRP, which is secreted by hepatocytes, is induced up to 1,000-fold during an acute-phase reaction. We have analyzed tolerance to hCRP expressed in transgenic mice under its autologous regulatory regions. Physiological regulation of basal levels (<10(-9) M) and inducibility (>500-fold) are preserved in female transgenics, whereas male transgenics constitutively display induced levels. Surprisingly, crossing of hCRP transgenic mice to two lines of T cell receptor transgenic mice (specific for either a dominant or a subdominant epitope) showed that tolerance is mediated by intrathymic deletion of immature thymocytes, irrespective of widely differing serum levels. In the absence of induction, hCRP expressed by thymic medullary epithelial cells rather than liver-derived hCRP is necessary and sufficient to induce tolerance. Importantly, medullary epithelial cells also express two homologous mouse acute-phase proteins. These results support a physiological role of "ectopic" thymic expression in tolerance induction to acute-phase proteins and possibly other inducible self-antigens and have implications for delineating the relative contributions of central versus peripheral tolerance.

Acute-Phase Proteins↗

PubMed1998

Wing development and specification of dorsal cell fates in the absence of apterous in Drosophila.

The development and patterning of the Drosophila wing relies on interactions between cell populations that have the anteroposterior (AP) axis and dorsoventral (DV) axis of the wing imaginal disc as frames of reference [1-3]. Each of these cell populations gives rise to a compartment - a group of cells that have their fates restricted by cell lineage - within which cells acquire specific identities through the expression of 'selector' genes [1,2,4]. The genes engrailed (en) and invected (inv), for example, label cells in the posterior compartment and mediate a set of cell interactions that direct the patterning and growth of the wing along the AP axis [1,2,4]. A similar situation has been proposed to exist across the DV axis, along with apterous (ap) as a dorsal selector gene [5], mediating cell interactions by regulating the expression of Serrate (Ser) [6] [7] and fringe (fng) [8]. In ap mutants, the wing is lost [5] [9], and here we report that this phenotype can be rescued by ectopic expression of either Ser or fng and that, surprisingly, the resulting wings have both dorsal and ventral cell fates.

Animals↗

PubMed1998

Different spatial and temporal interactions between Notch, wingless, and vestigial specify proximal and distal pattern elements of the wing in Drosophila.

The wing of Drosophila is composed of a proximal element, the hinge, which attaches it to the thorax, and a distal one, the wing blade. The development of the wing is a complex process that requires the integration of cellular responses to two signaling systems centered along the anteroposterior and the dorsoventral axes. The genes Notch (N) and wingless (wg) play an important role in generating the information from the dorsoventral axis. The vestigial (vg) gene is necessary for the development of the wing and is a target of these signaling systems during the growth of the wing. Here we examine the roles that N, wg, and vg play during the initial stages of wing development. Our results reveal that vg is involved in the specification of the wing primordium under the combined control of Notch and wingless signaling. Furthermore, we show that once cells are assigned to the wing fate, their development relies on a sequence of regulatory loops that involve N, wg, and vg. During this process, cells that are exposed to the activity of both wg and vg will become wing blade and those that are continuously under the influence of wg alone will develop as hinge. Our results also indicate that the growth of the cells in the wing blade results from a synergistic effect of the three genes N, wg, and vg on the cells that have been specified as wing blade.

Animals↗

PubMed1998

Expression of cyclooxygenase 1 and cyclooxygenase 2 in human synovial tissue: differential elevation of cyclooxygenase 2 in inflammatory joint diseases.

OBJECTIVE: To compare the expression of the cyclooxygenase (COX) isoforms, COX-1 and COX-2, in synovial tissue samples between patients with inflammatory arthritis (i.e., rheumatoid arthritis [RA], ankylosing spondylitis [AS], or psoriatic arthritis [PsA]) and patients with osteoarthritis (OA). METHODS: Paraffin-embedded sections of synovial tissue from patients with OA (n = 18), RA (n = 35), AS (n = 9), and PsA (n = 16) were immunostained for COX-1 and COX-2. Staining intensity was quantified videodensitometrically from specific synovial cell areas. In addition, samples of OA and RA synovial tissue were analyzed for levels of COX-1 and COX-2 messenger RNA (mRNA) using reverse transcriptase-polymerase chain reaction. RESULTS: Strong COX-2 immunostaining was observed in synovial blood vessel endothelium, synovial lining cells, chondrocytes, and subsynovial fibroblast-like cells in patients with inflammatory arthritides. In the blood vessels, the mean (+/-SD) optical density (MOD) of staining was elevated, especially in AS samples (2.73 +/- 0.63), but also in PsA (1.99 +/- 0.66) and RA samples (1.54 +/- 0.73), in comparison with OA synovial tissue (0.84 +/- 0.30; P < 0.01 versus other groups). COX-1 staining was almost exclusively localized in synovial lining cells, with no significant differences in the MOD between the diseases. COX-2 mRNA expression was higher in RA than in OA samples (P < 0.05). CONCLUSION: The expression of COX-2, but not the expression of COX-1, was found to be elevated in a disease-related pattern in the synovial tissue from patients with RA, AS, or PsA in comparison with OA samples, and was especially high in AS synovial tissue. These results may improve our understanding of the pathogenesis of different arthritic diseases, and may have implications for the use of selective COX-2 inhibitors in the treatment of inflammatory joint symptoms.

Adult↗

PubMed1998

Conjugation in archaea: frequent occurrence of conjugative plasmids in Sulfolobus.

We describe five novel conjugative plasmids (CPs) and two subfamilies, each comprising several closely related variants of CPs isolated from colony-cloned strains of the extremely thermophilic, heterotrophic archaeon Sulfolobus islandicus, which were obtained by plating of samples from Icelandic solfataras after liquid enrichment. They are related to each other and to the previously described CP pNOB8 from a Japanese Sulfolobus strain in that they share essential functions and limited similarity of genomes as demonstrated by DNA cross-hybridization and sequences. All these plasmids thus form a family of highly efficient self-spreading elements directly transferred from donor into recipient cells. Conjugation is initiated by pair formation, followed by selective transfer of the plasmids into the recipient and expression of transfer functions. Some of these CPs exclude superconjugation of the transcipients with closely related CPs. The novel CPs are stable upon conjugative transfer, but vary upon growth of transcipients. The stability of the CPs is higher in their original hosts or in related S. islandicus strains, than in Sulfolobus solfataricus strain PH1 as recipient. The deletion variant pING3 has lost the ability to transfer itself but is still subject to being transferred by the transfer apparatus of its complete relative, pING6. The dissection of genes and functions has been initiated by characterizing this incomplete variant.

Bacteriological Techniques↗

PubMed1998

The role of macrophages in THC-induced alteration of the cytokine network.

Delta-9-tetrahydrocannabinol (THC) has been shown to decrease Th1 responses (cell mediated immunity) while increasing Th2 responses (humoral immunity), both in vitro and in vivo. The addition of THC to murine splenocytes stimulated for 72 hrs with pokeweed mitogen (PWM) increased the detection of IL-4 and IL-10, cytokines associated with Th2 responses, and decreased IFN-gamma, IL-15 and IL-12, cytokines associated with Th1 responses. To investigate the cellular molecular basis for these effects of THC, cell depletion studies were performed. Removal of macrophages from the cell cultures eliminated the increase in IL-4 activity. This effect was observed when the macrophages were depleted during the first few hours but not after 24 hrs. Thus, it appears that the macrophages were producing an early factor responsible for the IL-4 increase. To examine the direct effect of THC on macrophages, peritoneal macrophages were cultured with various stimulators in the presence of THC. It was found that THC suppressed IL-12, IL-15 and IL-6 and increased IL-1 alpha, IL-1 beta, and TNF alpha in all of the stimulated cultures. IL-12 and IL-15 are known to induce IFN gamma production from T cells and NK cells and to be involved in the induction a Th1 response, while IL-1 is considered a growth factor for Th2 cells. Thus, the effects of THC on macrophages reflects the basic observation that THC decreases Th1 responses and increases Th2 responses. The data obtained adds to the understanding of the THC-induced Th1/Th2 shift, but the mechanisms still must be determined. However, the results of these studies do suggest that, in addition to lymphocytes, THC affects macrophages in splenocyte cultures and that the macrophages are involved in the alternation of the cytokines. Furthermore, the data demonstrate the diversity of the immunomodulatory effects THC exerts.

Adjuvants, Immunologic↗

PubMed1998

[Nursing home admission for the elderly and chances for avoiding admission. Results of a representative study of facilities for inpatient nursing care].

In this study the rate of institutionalization in old age for the first time is analyzed on a retrospective data set: the Altenheimsurvey and the Socio-Economic Panel-Survey. The study relies on 5,150 persons aged 60 and over. Based on these data, a variety of insufficiently answered questions were analyzed. Among the results, (1) the age increase of the institutionalization rate relies only to a minor extend on declining health and declining social networks, (2) the higher institutionalization rate of women is entirely ascribed to widowhood, and (3) non-familiar social networks are of minor importance.

Aged↗

PubMed1998

HLA-B38 and clozapine-induced agranulocytosis in Israeli Jewish schizophrenic patients.

To further substantiate reports of an association between the major histocompatibility complex subtypes and clozapine-induced agranulocytosis, HLA typing was performed in 61 Jewish Israeli schizophrenic patients, in 11 of whom agranulocytosis developed following clozapine treatment and in 50 (controls) of whom it did not. Of the 11 agranulocytosis patients, seven (63%) were of Ashkenazi origin and four (37%) of Sephardi origin. There was no difference in ethnic origin between the arganulocytosis and non-agranulocytosis groups (chi 2 = 2.4, d.f. = 1, P = 0.11), although the agranulocytosis patients had a higher frequency of the HLA B38 antigen (8/11 or 72% vs. 6/50 or 12%; chi 2 = 18.7, d.f. = 1, P < 0.001). These results suggest that major histocompatibility complex gene products could be involved in clozapine-mediated haematological complications.

Adult↗

PubMed1998

Interaction of IGF-I and 1 alpha, 25(OH)2D3 on receptor expression and growth stimulation in rat growth plate chondrocytes.

Growth plate cartilage cell express receptors for, and are affected by both IGF-I and 1 alpha, 25(OH)2D3. The studies were undertaken to investigate interaction between these two hormone systems, that is, (i) to study effects of 1 alpha, 25(OH)2D3 on IGF-type 1 receptors (IGFIR), on IGF-I stimulated cell replication, colony formation, and on alkaline phosphatase activity (AP), and conversely, (ii) to study the effect of IGF-I on vitamin D receptor (VDR) expression on 1 alpha, 25(OH)2D3 stimulated growth parameters and on AP activity. Freshly isolated rat tibial chondrocytes were grown in monolayer cultures, (serum-free) or in agarose stabilized suspension cultures (0.1% FCS). Vitamin D receptor and IGFIR were visualized by immunostaining with the monoclonal antibody (mAb) 9A7 gamma and mAb alpha IR3, respectively, and quantitated by RT-PCR for mRNA and by Scatchard analysis using [3H]-1,25(OH)2D3 and [125I]-alpha IR3. Cell proliferation was measured by [3H]-thymidine incorporation, growth curves in monolayer cultures, and by colony formation in agarose-stabilized suspension cultures. IGF-I dose-dependently increased [3H]-thymidine incorporation. 1 alpha, 25(OH)2D3, but not 1 beta, 25(OH)2D3 was stimulatory at low ((10-12 M) and slightly inhibitory at high (10-8 M) concentrations. The effect of IGF-I was additive to that of 1 alpha, 25 (OH)2D3 [IGF-I 60 ng/ml, 181 +/- 12.7; 1 alpha, 25(OH)2D3 10(-12) M, 181 +/- 9.8%, IGF-I + 1 alpha, 25(OH)2D3, 247 +/- 16.7%, P < 0.05 by ANOVA] and specifically obliterated by polyclonal IGF-I antibody (AB-1). Interaction could also be confirmed in suspension cultures. IGFIR mRNA and [125I]-alphaIR3 binding was increased by low (10(-12) m) but not by high (10(-8) M) concentrations of 1 alpha, 25(OH)2D3. Homologous up-regulation by IGF-I (60 ng/ml) was specifically inhibited by AB-1 and markedly amplified by coincubation with 1 alpha, 25(OH)2D3 (10(-12)m). Immunostaining with alpha IR3 showed specific IGFIR expression in rat growth cartilage, but not liver tissue. Stimulation of chondrocytes with 1 alpha, 25(OH)2D3 or IGF-I suggested some increase of receptor expression in single cells, but the predominant effect was increased recruitment of receptor positive cells, Vitamin D receptor expression was markedly stimulated (fourfold) by IGF-I (60 ng/ml), but not IGF-II and inhibited by actinomycin D. This study shows that IGF-I and 1 alpha, 25(OH)2D3 mutually up-regulate their respective receptors in growth plate chondrocytes. In parallel, they have additive effects on cell proliferation and colony formation suggesting independent effector pathways.

Animals↗

PubMed1998

On the induction of cyclooxygenase-2, inducible nitric oxide synthase and soluble phospholipase A2 in rat mesangial cells by a nonsteroidal anti-inflammatory drug: the role of cyclic AMP.

One of the challenges in the therapy with anti-inflammatory drugs is the avoidance of gastrointestinal side effects, which may be achieved by selective inhibition of cyclooxygenase (COX) -2. CGP 28238 is reported with these characteristics inhibiting selectively the COX-2 activity at nanomolar concentrations. However, we report here on a novel action of this compound uncovered during the application of higher concentrations. In rat mesangial cells, CGP 28238 induced the mRNA and the protein of COX-2 as well as those of inducible nitric oxide synthase and soluble phospholipase A2. In the case of COX-2, this stimulation had no effect on the production of COX-2 metabolites because of the effective blockade of the enzyme. In contrast, the level of NO produced by the cells increased in a concentration-dependent manner from 1.2 to 12.5 nmol of nitrite/3 x 10(5) cells. Furthermore, in combination with low doses of IL-1 CGP 28238 superinduced the formation of nitrite. The observed effects were independent of the inhibition of prostaglandin formation, as suggested by the failure of the potent COX inhibitor diclofenac to cause similar effects. Furthermore, the activity and expression of enzymes downstream of the COX step, such as prostacyclin synthase, were unaffected by CGP 28238. The inductive action of CGP 28238 could be blocked by inhibitors for tyrosine kinases and protein kinase A, such as genistein and KT5720, respectively. The increase in intracellular cAMP concentration in rat mesangial cells and the inhibition by CGP 28238 of phosphodiesterase 4 activity with an IC50 value of 23 muM gave a rationale to explain the underlying mechanisms for the induction of the inflammatory response genes COX-2, soluble phospholipase A2 and inducible NO synthase in rat mesangial cells.

Animals↗