Search PubMed⌕ Search

Biomedical subjects

S Lang

Publications and source records attributed to S Lang.

At least 91 records · Page 5Linked to original sources

Prostatic ductal system in rats: changes in regional distribution of extracellular matrix proteins during castration-induced regression.

BACKGROUND: The extracellular matrix (ECM) is an intricate network composed of an array of molecules that play an integral role in the regulation of cell function, differentiation, and tissue-specific gene expression in various epithelia. In the present study, we examined the distribution of collagen type IV and laminin along the rat ventral prostatic duct before and after castration. METHODS: Mature Sprague-Dawley rats were castrated and their prostates processed for immunocytochemistry of ECM proteins, laminin, and collagen type IV. Tissue sections were also processed for apoptosis staining, using the 3' end-labeling technique. To examine the effect of ECM proteins on epithelial growth, rat ventral epithelial cells were cultured on ECM-coated surfaces. RESULTS: In the intact rat, laminin was localized in the basement membrane along all regions of the ventral prostate ductal system. Collagen type IV was found to be distributed evenly in the basement membrane of the distal and intermediate regions but was absent or poorly organized in the proximal region, where apoptosis in the epithelium occurs at a high rate. In the regressing prostate after castration, there was a shift in apoptosis from the proximal region to the distal intermediate regions of the prostatic duct. Associated with the shift was a remodeling of basement membrane proteins due to the specific loss of collagen type IV in the distal and intermediate regions. Collagen type IV reappeared underneath the epithelium 7 days after castration, when apoptosis in the epithelium stopped. In vitro, collagen type IV enhanced the growth of ventral prostatic epithelial cells, as assessed by cell number. CONCLUSIONS: Collagen basement membrane type IV mediates growth of rat ventral prostate epithelium, and its loss during tissue remodeling after castration is associated with cell death.

Animals↗

Validation of excised bovine nasal mucosa as in vitro model to study drug transport and metabolic pathways in nasal epithelium.

The present work aims at the validation of excised bovine nasal mucosa as an in vitro model to address transport and metabolism pathways relative to the nasal mucosal uptake of therapeutic peptides. Preservation of the viability of the excised tissue in the course of in vitro studies of up to 3 h was demonstrated by (i) positive viability staining, (ii) constant transepithelial electrical resistance (42 +/- 12 Omega cm(2)), (iii) constant rates of metabolic turnover, and (iv) linear permeation profiles of therapeutic peptides and (3)H-mannitol. Using 1-leucine-4-methoxy-2-naphthylamide as a model substrate, we observed no difference between bovine and human nasal aminopeptidase activity. By a series of therapeutic peptides, no direct correlation was found between their effective permeability coefficients (from 0. 1 x 10(-5) to 5 x 10(-5) cm s(-1)) and their respective molecular masses (from 417 to 3,432 Da), indicating that other factors dominate nasal permeability. For instance, the permeabilities of metabolically labile peptides were concentration dependent and saturable, as demonstrated for two short thymopoietin fragments, Arg-Lys-Asp (TP3) and Arg-Lys-Asp-Val (TP4). By permeation studies using gonadorelin and two gonadorelin derivatives, buserelin and Hoe 013, without and in the presence of the chemical enhancer bacitracin, we also verified the ability of the model to assess chemical enhancer effects and their reversibility. In conclusion, our work demonstrates the potential of the investigated in vitro model, excised bovine nasal mucosa, to explore mechanistic aspects of nasal transport and metabolism of therapeutic peptides.

Absorption↗

Possible cocarcinogenic effects of ELF electromagnetic fields may require repeated long-term interaction with known carcinogenic factors.

Literature on cancer-related biological effects of extremely low frequency (ELF) magnetic fields (MF) is discussed in the light of the current understanding of carcinogenesis as a multistep process of accumulating mutations. Different animal models and study designs have been used to address possible cocarcinogenic effects of MFs. Based on a comparison of the results, we propose a hypothesis that MF exposure may potentiate the effects of known carcinogens only when both exposures are chronic. We also discuss possible mechanisms of MF effects on carcinogenesis and the adequacy of the classical two-step initiation/promotion animal experiments for simulating human exposure to the complex mixture of environmental carcinogens. We conclude that experiments designed according to the two-step concept may not be sufficient for studying the possible role of MF in carcinogenesis. Possible further animal studies are more likely to be productive if they include models that combine chronic exposure to MFs with long-term exposures to known carcinogens.

Animals↗

Early versus delayed initiation of breastfeeding.

EDITORIAL NOTE: This review has been withdrawn because it is out of date. The topic will be covered by a new review, 'The effect of the timing of feedings on the establishment of breastfeeding', the protocol for which is currently being prepared. BACKGROUND: It has been suggested that the timing of a baby's first breastfeed may influence breastfeeding duration and emotional attachment. OBJECTIVES: The objective of this review was to assess the effects of breastfeeding soon after birth (within 30 minutes) compared to being breastfed later (between 4 to 8 hours after delivery) on the duration of breastfeeding and the mother/infant relationship. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing early skin contact and breastfeeding with late skin contact and breastfeeding in women intending to breastfeed their healthy term infant. DATA COLLECTION AND ANALYSIS: Data were extracted by two reviewers. MAIN RESULTS: Three studies involving 209 women were included. Compared with late contact and breastfeeding, early contact and breastfeeding was associated with greater communication between mother and infants in a two minute observation period (odds ratio 0.14, 95% confidence interval 0.03 to 0.61). There was no difference detected for numbers of women breastfeeding after birth (odds ratio for 12 weeks after birth 0.73, 95% confidence interval 0.34 to 1.54). REVIEWER'S CONCLUSIONS: No differences were found between early and delayed contact in regard to breastfeeding duration. Early contact was associated with greater communication between mothers and infants.

Breast Feeding↗

Feeding schedules in hospitals for newborn infants.

BACKGROUND: Regular breastfeeding times have been thought to help establish routines and promote infant digestion, while frequent breastfeeding has been recommended to enhance breastfeeding and infant growth. OBJECTIVES: The objective of this review was to assess the effects of frequent breastfeeding compared with less frequent breastfeeding in the early days after birth. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing on demand or frequent breastfeeding (two or three hourly) schedules in hospital compared with four hourly restricted feeds. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. MAIN RESULTS: Three trials involving 400 women were included. There were significant methodological limitations in some of the studies. Compared to two hourly, three hourly or on demand breastfeeding, restricted (less frequent four hourly breastfeeding) was associated with greater discontinuation of breastfeeding by four to six weeks postpartum (relative risk 1.53, 95% confidence interval 1.08 to 2.15). Restricted breastfeeding was associated with increased incidence of sore nipples (relative risk 2.12, 95% confidence interval 1.22 to 3.68), engorgement (relative risk 2.10, 95% confidence interval 1.25 to 3.21) and the need to give additional (formula) feeds (relative risk 3.14, 95% 1.24 to 8.00). REVIEWER'S CONCLUSIONS: There appear to be a number of disadvantages from restricting breastfeeding to a four hourly schedule in the first few days after birth. More frequent or on demand breastfeeding is associated with fewer complications and longer duration of breastfeeding.

Breast Feeding↗

Interventions for influencing sleep patterns in exclusively breastfed infants.

BACKGROUND: The difference between night and day may be reinforced in young babies by offering a 'focal feed' between 10pm and midnight and gradually lengthening the intervals between night-time feeds by a variety of other activities (such as nappy changing, re-swaddling and walking with the infant). OBJECTIVES: The objective of this review was to assess the effects of using a structured training programme to teach exclusively breastfed infants to sleep through the night by eight weeks old. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register. SELECTION CRITERIA: Acceptably controlled trials of a structured programme accentuating the difference between night and day compared with no intervention in first time parents of singleton babies, with mothers intending to exclusively breastfeed their infants for at least eight weeks post-partum. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. MAIN RESULTS: One trial involving 33 couples was included. More infants in the treatment group were sleeping throughout the night by eight weeks of age than in the control group (odds ratio 0.04, 95% confidence interval 0.01 to 0.21). REVIEWER'S CONCLUSIONS: There is some evidence to show that first time parents using a structured sleeping programme can teach their babies to sleep through the night by eight weeks of age.

Breast Feeding↗

Oxytocin for promoting successful lactation.

BACKGROUND: A rise in the concentration of oxytocin causes contraction of cells around the alveoli and milk ducts, in preparation for suckling. Lactation failure may result from insufficient oxytocin. OBJECTIVES: The objective of this review was to assess the effects of using oral or nasal oxytocin on lactation. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register. SELECTION CRITERIA: Randomised and quasi-randomised trials of variable doses of oxytocin and different methods of administration versus placebo in breastfeeding women using oxytocin to augment lactation. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted by two reviewers. MAIN RESULTS: Four trials of 639 women were included. There was potential for significant bias in these trials. Restricted breastfeeding schedules may have contributed to inadequate production of milk by the participants. Sublingual and buccal preparations of oxytocin were associated with an increase in milk production. Oxytocin did not appear to increase the incidence of breast pain and 100 international units of oxytocin appeared to be slightly more beneficial than 10 international units. REVIEWER'S CONCLUSIONS: An appropriate dose of sublingual or buccal oxytocin may help augment lactation where necessary. However if women are encouraged and supported with unrestricted breastfeeding, the need for oxytocin would probably be diminished.

Female↗

Chemical shift imaging with continuously flowing hyperpolarized xenon for the characterization of materials.

In this contribution we report new approaches to the MRI of materials using continuously produced laser-polarized (129)Xe gas. This leads to vastly improved sensitivity and makes new kinds of information available. The hyperpolarized xenon is produced in a continuous flow system that conveniently delivers the xenon at low partial pressure to probes for NMR and MRI experiments. We illustrate applications to the study of micropore and other kinds of void space and show for the first time that with flowing hyperpolarized xenon it is possible to obtain chemical-shift-resolved images in a relatively short time.

Calcium↗

Heat shock protein 72 expression in chondrosarcoma correlates with differentiation.

PURPOSE: Heat shock proteins (hsp) are involved in tumor immunity, and a correlation with survival, occurrence of metastases, and drug resistance has been reported. It was the aim of this study to investigate the expression of heat shock proteins in chondrosarcomas and chondromas. METHODS: Hsp expression was investigated immunohistochemically on paraffin-embedded sections of 37 consecutive patients (24 male and 13 female, mean age 48 years) with chondrosarcoma and of ten patients (six male, four female, mean age 36 years) with chondroma. RESULTS: Chondromas showed a positive staining for hsp27 in 100%, for hsp60 in 30%, for hsp72 in 80%, for hsp73 in 80%, and for hsp90 in 90%. In chondrosarcoma a decreased expression was found for hsp27 (62% positive, P<0.05) and hsp72 (43% positive, P<0.05), whereas no significant difference to chondromas was detected in the expression of hsp60 (49% positive), hsp73 and hsp90 (73% and 81% positive, respectively). In addition, hsp72 expression showed a correlation with differentiation of the tumors (P<0.05); the lowest hsp72 expression was found in G3 chondrosarcomas (only 13% positive). No correlation with respect to differentiation was found for the expression of the other hsps. CONCLUSIONS: This study shows a different expression of hsps in chondrosarcomas and chondromas. Together with the correlation of hsp72 expression with low differentiation, this finding could lead to new experimental and diagnostic strategies.

Adolescent↗

Production and structure elucidation of glycoglycerolipids from a marine sponge-associated microbacterium species.

The bacterium Microbacterium sp., isolated from the sponge Halichondria panicea, produced four unusual cell-associated glycoglycerolipids and one diphosphatidylglycerol when grown on marine broth and on artificial seawater media. The lipids were isolated by chromatography on silica columns and their structures elucidated using a combination of multidimensional NMR and MS techniques. The main compound was 1-O-acyl-3-[alpha-glucopyranosyl-(1-3)-(6-O-acyl-alpha-mannopyranosyl )]glycerol (GGL.2) with 14-methyl-hexadecanoic acid and 12-methyl-tetradecanoic acid positioned at C-6 of the mannose unit and at the glycerol moiety. Glycolipid production was correlated with growth and reached a maximum value of 200 mg/L when grown on artificial seawater medium with 20 g/L glucose. The main compound decreased the surface tension of water down to 33 mN/m and the interfacial tension of the water/n-hexadecane system down to 5 mN/m. In addition to this good surface-active behavior, the main glycoglycerolipid showed antitumor activities.

Actinomycetales↗

Platelet-derived growth factor-AA and -alpha receptor expression suggests an autocrine and/or paracrine loop in osteosarcoma.

Platelet-derived growth factor (PDGF) is a major mitogen and chemotactic factor for mesenchymal cells such as fibroblasts, smooth muscle cells, and osteoblasts. PDGF exists as disulfide-linked homo- or heterodimers composed of two polypeptide chains encoded by distinct genes, designated PDGF-A and PDGF-B. Upon binding to its tyrosine kinase receptor PDGF-alpha, especially PDGF-AA stimulates the proliferation of osteoblastic cells and may exert autocrine and paracrine effects in regulating bone-forming processes. The purpose of this immunohistochemical study was to determine the expression of PDGF-AA and PDGF-alpha receptor in benign and malignant neoplastic bone lesions. Polyclonal antibodies to PDGF-AA and PDGF-alpha receptor were used on paraffin sections of 23 osteosarcomas and 17 osteoblastomas. Immunostaining was assessed quantitatively by evaluating the percentage of reactive tumor cells. In osteosarcomas, the mean expression of PDGF-AA and PDGF-alpha receptor was 33.97% (range, 2 to 80%; SD, 24.26%) and 27.13% (range, 3.2 to 72%; SD, 18.38%), respectively. Osteoblastomas showed significantly lower expression of PDGF-AA than osteosarcomas (mean, 15.71%; range, 5 to 34%; SD, 9.43%; P = .019). Although the mean expression of PDGF-alpha receptor in osteoblastomas was much lower than in osteosarcomas (mean, 17.55%; range, 3.6 to 26.8%; SD, 6.47%), the difference was not significant (P = .122). For osteosarcomas, Spearman correlation coefficient (two-tailed) revealed a significant correlation between the expression of PDGF-AA and PDGF-alpha receptor (r = .688), which was not the case for osteoblastomas (r = .267). These data suggest that in contrast to osteoblastoma, the growth of osteosarcoma may be supported by the coordinate expression of the potent mitogenic growth factor and its receptor that exert their functions by autocrine and paracrine mechanisms.

Autocrine Communication↗

Consistency of histopathological reporting of laryngeal dysplasia. The Scottish Pathology Consistency Group.

AIMS: Clinical management of premalignant and malignant lesions of the larynx is dependent on histopathological evaluation. The Scottish Pathology Consistency Group assessed interobserver variation in the evaluation of laryngeal dysplasia. METHODS AND RESULTS: One hundred laryngeal biopsies ranging from normal to invasive carcinoma were assessed. The overall Kappa result of 0.32 was disappointing. However, agreement on those categories which dictate significantly different management was more favourable. The Kappa figure for mild dysplasia versus severe dysplasia/CIS was 0.7, the Kappa figure for mild dysplasia versus severe dysplasia/CIS and invasive carcinoma was 0.77. The Kappa figure for mild and moderate dysplasia versus severe dysplasia/ CIS and invasive carcinoma was 0.57. An attempt to use a two grade system gave a Kappa figure of 0.52. CONCLUSIONS: Our group had a satisfactory agreement on the distinction of mild from severe dysplasia and on microinvasive carcinoma without any discussion as to histopathological criteria to be used. Clinical management--review endoscopy, repeat cord stripping, radiotherapy and laryngectomy--is in general dependent on histological assessment. Thus the agreement on categories which underpin clinical management is reassuring. However, assessment of moderate dysplasia remains problematic. An attempt to utilize a two grade system--low grade from high grade dysplasia/CIS--may have merit. The implications of the terminology used must be agreed among pathologists and clinicians working closely within clinicopathological cancer groups.

Adenocarcinoma↗

Periosteal osteoblastoma: a case report and a review of the literature.

Osteoblastomas located on the surface of cortical bone, so-called periosteal (juxtacortical) osteoblastomas, are extremely rare. A 24-year-old man complained of pain and swelling in the left knee. The clinical and radiological investigation showed a tumor located in the posterior portion of the distal shaft of the femur. The radiological differential diagnosis included parosteal osteosarcoma, periosteal chondroma and periostitis ossificans. A frozen section was obtained and histology revealed an osteoblastoma with large epithelioid-appearing osteoblasts consistent with an aggressive osteoblastoma. An en bloc resection of the tumor was performed and the definitive histology of the whole specimen revealed a typical osteoblastoma. The authors draw attention to the fact that periosteal osteoblastoma is a rare tumor that could be mistaken clinically and histologically for other and more common tumors at this location.

Adult↗

Distinct structural forms of type I collagen modulate cell cycle regulatory proteins in mesangial cells.

BACKGROUND: Extracellular matrix molecules profoundly regulate cell behavior, including proliferation. In glomerulonephritis, type I collagen accumulates in the mesangium and is constantly structurally modified and degraded during the course of the disease. METHODS: We studied how two structurally distinct forms of type I collagen, monomer versus polymerized fibrils, affect cell proliferation, mitogen-activated protein kinase (MAPK) activation, and expression of G1-phase regulatory proteins in cultured rat mesangial cells (MCs). To analyze the possible involvement of collagen-binding integrins in type I collagen-derived growth signals further, distribution patterns of integrin chains were examined by immunocytochemistry. RESULTS: Polymerized type I collagen completely prevented the increase of DNA synthesis and cell replication induced by 5% fetal calf serum (FCS) or 25 ng/mL platelet-derived growth factor (PDGF) in MCs on monomer type I collagen. Protein expression of cyclins D1 and E was markedly down-regulated in MCs plated on polymerized type I collagen for eight hours in 5% FCS, as compared with MCs on monomer type I collagen. Incubation with 5% FCS reduced expression of the cdk-inhibitor protein p27Kip1 on monomer but not on polymerized type I collagen. Moreover, polymerized type I collagen markedly reduced cyclin E-associated kinase activity in the presence of 5% FCS. Polymerized type I collagen diminished the PDGF-induced phosphorylation and nuclear translocation of p42/p44 MAPK, but did not affect phosphorylation of PDGF beta-receptors. In MCs plated on monomer type I collagen, alpha1, alpha2, and beta1 integrin chains were recruited into focal contacts. However, on polymerized type I collagen, alpha2 and beta1, but not alpha1, integrin chains were condensed into focal contacts. CONCLUSIONS: The growth-inhibitory effect of polymerized type I collagen is characterized by rapid changes of expression and/or activation of MAPK and G1-phase regulators and could result from the lack of alpha1beta1 integrin signaling in MCs on polymerized type I collagen. Conceivably, deposition of polymerized type I collagen might reflect a reparative response to control MC replication in glomerular inflammation.

Animals↗

[The interesting case No. 39. Differential diagnosis of acute antibiotic-resistant pharyngitis].

We report on a 41-year old female patient presenting a history of long-term sore throat, in addition to ulcers on both tonsils, the base of the tongue, the hypopharyngeal mucosa, and a laryngeal edema. She underwent diagnostic tonsillectomy and microlaryngoscopy on the suspicion of malignancy. Clinical and histopathological investigations demonstrated granulomatous inflammation with necrosis containing acid-fast rods in the tissue specimens. Furthermore, the presence of acid-fast bacilli in the bronchial lavage suggested the diagnosis of a possibly reactivated pulmonary tuberculosis. The present case provides evidence that pharyngeal tuberculosis may represent the first manifestation of tuberculosis. Therefore, the differential diagnosis of nonspecific symptoms such as sore throat should include tuberculosis as a causative factor.

Acute Disease↗

Antigen contacts by Ni-reactive TCR: typical alphass chain cooperation versus alpha chain-dominated specificity.

VB17(+) TCR dominate in Ni-driven T cell cultures from highly Ni-sensitized patients. Using transfection of TCR from three CD4(+), VB17(+), Ni-specific human T cell clones, we studied their Ni-MHC contacts by site-directed TCR mutation and combination of alpha and ss chains between different TCR. All three TCR exhibited N-nucleotide-determined Arg-Asp motifs in their CDR3-ss sequences. Two of them were specifically restricted to HLA-DR13, while the third one accepted a variety of HLA-DR alleles. The highly similar alpha or ss chains of the DR13-restricted TCR were interchangable without loss of specificity, but alpha or ss chains of other TCR were not tolerated. Mutations of their Arg-Asp motif revealed loss of reactivity upon exchanging Asp for Glu or Ala and of Arg for Ala but not of Arg for Lys or the Ni binding His. Reactivity was also destroyed by mutation of alpha chain position 51, proposed as a general contact site for MHC. Hence, in these two TCR the Arg-Asp motif is clearly involved in contacting Ni-MHC complexes, and close cooperation between alpha and ss chain is required. In contrast, the third TCR retained Ni reactivity upon mutation of alpha chain position 51 or of its ss chain Arg-Asp motif, which rather affected the pattern of DR cross-restriction. Moreover, its alpha chain paired with various ss chains from other, even mouse TCR, irrespective of their specificity, retaining Ni reactivity as well as promiscuous HLA-DR restriction. This preponderance of an alpha chain in defining specificity indicates fundamental differences in Ni interactions of individual TCR and implies that ss chain similarities may not necessarily result from antigen selection.

Alleles↗

Tumor cell-derived prostaglandin E2 inhibits monocyte function by interfering with CCR5 and Mac-1.

The cyclooxygenases (COX)-1 and COX-2 are key enzymes in the conversion of arachidonic acid to prostaglandins and other eicosanoids. Whereas COX-1 is expressed ubiquitously, COX-2 is an immediate-early gene often associated with malignant transformation, and a role for the COX enzymes in tumor initiation and promotion is discussed. Nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin and indomethacin that block COX-1 and -2 have been shown to have beneficial effects for tumor patients. Therefore, these compounds have gained interest also among oncologists. However, the molecular mechanism by which NSAIDs inhibit carcinogenesis is not clearly understood. The prostaglandin-dependent and -independent effect may both account for their antineoplastic action. We show here that tumor cells derived from different tumors regularly produce prostaglandin E(2) (PGE(2)) interfering with the function of monocytes. In particular, PGE(2) inhibits the potential of monocytes to migrate in the direction of a chemotactic stimulus and to adhere to endothelial cell. This inhibition is most probably due to a modulation of the chemokine receptor CCR5 and the beta2-integrin Mac-1. Both down-regulation of CCR5 and reduced expression of Mac-1 may diminish the potential of peripheral blood monocytes to leave blood vessels and invade target tissues. Since both dysfunctions can be restored with NSAIDs, our findings help to explain the molecular chemopreventive action of NSAIDs on tumor formation and progression.

Anti-Inflammatory Agents, Non-Steroidal↗

Identification of a novel antigen from Staphylococcus epidermidis.

A genomic DNA library of Staphylococcus epidermidis NCTC 11047 was constructed, using the Lambda Zap Express cloning vector, and screened with serum collected from a patient with S. epidermidis endocarditis. Sequence analysis of a 30 kDa cloned protein, termed staphylococcal secretory antigen, SsaA, identified a novel protein not previously reported in S. epidermidis. SsaA showed strong homology with two other staphylococcal proteins: SceB from Staphylococcus carnosus and a staphyloxanthin biosynthesis protein from Staphylococcus aureus. Further investigation revealed SsaA to be a highly antigenic protein that was expressed in vivo and could be recovered from whole cells and from the culture supernatant. A combination of Western blot analysis and PCR screening identified SsaA or a homologue in 103/103 staphylococcal strains. SsaA-like genes were not detected in other Gram-positive bacteria of medical importance or a number of Gram-negative organisms. Elevated anti-SsaA IgG antibody levels were detected in sera of five patients with S. epidermidis endocarditis but not in patients with other S. epidermidis infections, endocarditis of other aetiologies or patients with no evidence of infection. The expression of SsaA during episodes of S. epidermidis endocarditis suggests a virulence role specific to the pathogenesis of this infectious disease.

Amino Acid Sequence↗