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Biomedical subjects

C Lang

Publications and source records attributed to C Lang.

At least 37 records · Page 2Linked to original sources

Correlation of nasal morphology and respiratory function.

In order to investigate the fluid dynamic preconditions that guarantee a sufficient contact of air with nasal mucosa, we studied flow patterns in modified "Mink's boxes" and in nasal models. As a result, the nose can be divided into 1) a functional area, i.e. area of turbinates, 2) an inflow area, i.e. vestibulum, isthmus and anterior cavum and 3) an outflow area, i.e. posterior cavum, choanae and epipharynx. The vestibulum is shaped like and acts as a bend, redirecting air to the cavum, and as a nozzle, reducing turbulence. With its concavely curved shape, the isthmus facilitates equal distribution of air throughout the entire area of the turbinates. The anterior cavum acts as a diffuser, where turbulence increases and velocity decreases. In the slit-like space of the area of turbinates, the flow behavior is determined by flow dynamics in the inflow area. The structure elements of the outflow area are similar to those of the inflow area but lined up in an inverse order.

Humans↗

Perspectives in the biological function and the technological application of polygalacturonases.

Polygalacturonases (PG) have evolved in the past years from a pectinase "simply" being used for food processing to an important parameter in plant-fungal interaction. PG-inhibiting proteins (PGIP) that are synthesised in plants as a specific response to PGs of pathogenic fungi, have become a focus as a possible target in resistance breeding, and PGIPs are also a concern as an inhibiting factor in food processing. Plant PGs have been identified as a major factor in fruit ripening, and PG-deficient transgenic plants have been bred. Mainly fungal PGs are used in industrial processes for juice clarification and the range of enzymes is being extended through new recombinant and non-recombinant fungal strains. Finally, novel fields of application can be envisaged for PGs in the production of oligogalacturonides as functional food components. Here we aim to highlight the various fields where PGs are encountered and where they are of biological or technological importance.

Food Technology↗

The influence of the ACE inhibitor lisinopril on the glomerular metabolism of proteolytic enzymes in diabetic rats.

Clinical studies indicate a nephro-protective effect in conjunction with the use of ACE inhibitors. This study's aim was to determine whether ACE inhibitors influence the metabolism of glomerular cells in addition to their known hemodynamic effects. Streptozotocin diabetic rats were treated with lisinopril (DLis 1.5 mg/l water), or hydralazine (Dhyd, 50 mg/l water) over 4 weeks. Untreated diabetic rats (DC) and non-diabetic rats (C) served as controls. After four weeks of treatment, urinary excretion of albumin, blood pressure and metabolic control (Glyc-Hb) were measured. After treatment glomeruli were isolated and homogenized, and beta-NAG and total proteolytic activity against azocasein were measured. Glycated hemoglobin levels were similar in all diabetic groups (DC, 12%, Dhyd, 10%; DLis 11%). Blood pressure of DLis rats (79 +/- 3 mmHg) and DHyd rats (46 +/- 2 mmHg) was lower than that of DC rats (111 +/- 3 mmHg). Urinary albumin excretion of diabetic groups was lowest in DLis. Diabetic rats showed a decrease in glomerular beta-NAG (10 vs. 60.5 U/g protein) and total proteolytic activity against azocasein (148 vs. 170 U/mg protein hour) compared to non-diabetic rats. Lisinopril increased beta-NAG (30 vs. 14 U/g protein) and total proteolytic activity (160.5 vs. 141.5 U/mg protein hour) compared with hydralazine. Our study confirms that the nephro-protective effect of ACE inhibitors is partially due to modulatory effects on the metabolism of basement membrane proteins.

Acetylglucosaminidase↗

Relationship between hepatic mitochondrial functions in vivo and in vitro in rats with carbon tetrachloride-induced liver cirrhosis.

BACKGROUND/AIMS: The metabolic capacity of liver mitochondria is impaired in rats with carbon tetrachloride (CCl4)-induced cirrhosis. These studies were performed to find out whether benzoate and/or palmitate are suitable substrates for assessing hepatic mitochondrial function in vivo. METHODS: In vivo metabolism of benzoate and 1-14C-palmitate was assessed by monitoring urinary excretion of hippurate and exhalation of 14CO2, respectively, in cirrhotic and control rats (n=8 for each group). Isolation of liver mitochondria, and in vitro benzoate and palmitate metabolism were performed by methods published previously. The hepatic content of mitochondria was assessed by stereological analysis of the volume of hepatocytes and by biochemical determination, using the activity of citrate synthase. RESULTS: Renal excretion of hippurate following i.p. administration of benzoate was reduced in cirrhotic rats (64+/-15 vs. 85+/-14% of administered dose over 24 h), and showed a linear correlation with hippurate formation by isolated mitochondria. The activities of benzoyl-CoA synthase and benzoyl-CoA:glycine N-acyltransferase were reduced by approximately 60%, and the coenzyme A content by 50% in hepatic mitochondria from cirrhotic rats, explaining impaired hippurate formation. Peak exhalation of 14CO2 after i.p. administration of 1-14C-palmitate was reduced by 44% and the area under the 14CO2 exhalation-time curve by 34% in cirrhotic rats. Peak 14CO2 exhalation revealed a linear correlation with oxidative metabolism of palmitoylcarnitine in isolated mitochondria. Both in vivo benzoate and palmitate metabolism showed a linear correlation with the volume fraction of hepatocytes. The mitochondrial protein content was reduced in cirrhotic rats per g liver and per liver but equal to control rats per volume of hepatocytes. CONCLUSIONS: In vivo metabolism of both palmitate and benzoate reflects hepatic mitochondrial function in rats with CCl4-induced cirrhosis. Hepatic mitochondrial function is impaired in rats with CCl4-induced cirrhosis due to both reduced mitochondrial volume per liver and impaired metabolism of the remaining mitochondria. In contrast to rats with secondary biliary cirrhosis, rats with CCl4-induced cirrhosis showed no hepatic mitochondrial proliferation to counteract reduced mitochondrial function.

Animals↗

Conformations in solution and bound to bacterial ribosomes of ketolides, HMR 3647 (telithromycin) and RU 72366: a new class of highly potent antibacterials.

The new class of antibiotics called ketolides is endowed with remarkable antibacterial activity against macrolide-resistant strains. Further modifications of the 3 keto-macrolactone backbone led to 11,12-hydrazonocarbamate ketolides with an imidazolyl pyridine chain: the file-leader of ketolide class, HMR 3647 (telithromycin), and its N-bis-demethyl-derivative, RU 72366. The potency of HMR 3647 is higher than that of RU 72366. Stereospecific 1H and 13C resonance assignments of HMR 3647 and RU 72366 have been determined and have allowed a detailed quantitative conformational analysis of the uncomplexed form of the molecules. The comparative conformation of HMR 3647 in solution and its N-bis-demethyl-derivative in D2O has been carried out using different heteronuclear correlation experiments in conjunction with nuclear Overhauser effect experiments and in particular long-range 3J(CH) coupling constants and using molecular dynamics (MD) methods. The study of ketolide ribosome interaction has been investigated using two-dimensional transferred nuclear Overhauser effect spectroscopy (TRNOESY). The database of ribosome-bound ketolide structures has been used to compare the structure(s) of ketolide in ribosome-ketolide complexes with the conformational preferences of free ketolides and to highlight the significant differences between HMR 3647 and RU 72366. A comparison of the conformations bound to ribosome was made with those of other previously studied ketolide (RU 004) and macrolides and would explain the remarkable potencies of HMR 3647 in inhibiting protein synthesis.

Anti-Bacterial Agents↗

[Manifestation of Creutzfeldt-Jakob disease 30 years after corneal transplantation].

BACKGROUND: Creutzfeldt-Jakob disease, currently viewed as one of the prionic diseases, occurs in by far the majority of cases sporadically, sometimes in families, and in rare instances as a transmissible disease with every conceivable interval of latency. HISTORY AND SIGNS: This report of a 45-year-old female concerns a spongiform encephalopathy which appeared almost 30 years after penetrating keratoplasty. The corneal material came from a 63-year-old donor with Creutzfeldt-Jakob disease; the keratoplasty was performed at a time when the transmissibility of certain diseases was still unknown. CONCLUSION: The risk of transmission of the disease is very low but cannot be ruled out.

Creutzfeldt-Jakob Syndrome↗

[The Susac syndrome--a retinocochleocerebral angiopathy].

INTRODUCTION: There has been a series of case reports of otherwise healthy patients suffering from microangiopathy of the brain, retina and cochlea. Most patients were young women presenting clinically with a subacute encephalopathy, branch retina artery occlusions, and hearing loss. In 1994 the name "Susac syndrome" has been proposed for this disease entity. METHOD: Case report and review of 64 published cases, identified through MEDLINE are given. CASE REPORT: We describe a 32-year-old otherwise healthy woman presenting with a subacute encephalopathy, multiple branch retinal artery occlusions and bilateral hearing loss. MRI of the brain revealed multiple small white and grey matter lesions without contrast enhancement. CSF protein was elevated, oligoclonal bands were negative. Immunological laboratory parameters, microbiology, virology, coagulation studies, SEP, AEP, VEP and cerebral DSA were normal. REVIEW OF THE LITERATURE: Of 64 identified patients 58 were women. The mean age of the patients was 30 years. 60 patients (94%) had arterial occlusions, which were bilateral in 39%. 48 patients reported hearing loss, 37 patients (58%) had a global encephalopathy, but other neurologic manifestations were common. CONCLUSION: This rare syndrome has a strong young female preponderance. MRI of the brain often shows lesions suggestive of multiple sclerosis. Fluorescein angiography may show arteriolar wall hyperfluorescence. Patients can be identified at an early stage with a careful history and physical examination. Early treatment with corticosteroids is often associated with a good prognosis. Cyclophosphamide and antiplatelet drugs may be added in complicated cases.

Adult↗

Epidural ropivacaine with fentanyl following major gynaecological surgery: the effect of volume and concentration on pain relief and motor impairment.

In a prospective, randomized, double-blind study, 40 patients undergoing gynaecological oncology surgery received either 0.1% ropivacaine with fentanyl 1 microgram ml-1 or 0.2% ropivacaine with fentanyl 2 micrograms ml-1. A PCEA pump was set to deliver ropivacaine 8 mg with fentanyl 8 micrograms with each successful demand and a lockout period of 15 min without background infusion. Patients were observed for rest and activity pain VAS, side effect incidence, peak expiratory flow rate (PEFR), leg strength, sensory block to cold and pinprick, and PCEA usage into the second postoperative day. Passive and active pain scores for both groups were both satisfactory and comparable for the duration of the study. There were no differences between groups with regard to side effects. There was a 24% increase in total drug used in the high-concentration/low-volume group (P < 0.05). The study demonstrated that PCEA ropivacaine with fentanyl is an effective means of postoperative analgesia for this patient population. Reduced drug consumption with high-volume/low-concentration solution confirms similar findings by other investigators using alternate local anaesthetic agents, and suggests that the therapeutic ratio of ropivacaine is widened if a low-concentration/high-volume solution is used.

Adult↗

Tenoxicam i.v. in major gynaecological surgery--pharmacokinetic, pain relief and haematological effects.

This study compared postoperative analgesic dispensation and measures relating to haemostasis following intravenous administration, in a randomized double-blinded manner, of either placebo or tenoxicam 20 mg to 30 women presenting for major gynaecological oncology surgery under a standardized, combined epidural/general anaesthetic technique. Pharmacokinetic disposition of tenoxicam in this patient cohort was also described. There was no objective or subjective alteration in haemostatic function or increase in blood loss, nor any deviation from the normal range of values. Postoperative analgesia during the first 48 hours was delivered to achieve a VAS endpoint of less than five on leg-raising, by a combination of a nurse-controlled low-dose background epidural infusion and patient-administered epidural bolus. Greater VAS variability was observed during the first four postoperative hours (P = 0.08). The tenoxicam group self-administered significantly fewer epidural bolus doses to maintain satisfactory analgesia compared with the placebo group during the first 24 hours (P = 0.004) and 48 hours (P = 0.01) postoperatively. Similar differences between the groups in the total dose of the epidural bupivacaine/fentanyl mixture delivered were described (4 h: P = 0.148; 24 h: P = 0.033; 48 h: P = 0.001) (Figure 2). Despite surgery, transfusion and the use of a renal protective fluid administration strategy, tenoxicam disposition was not greatly different from that widely described for healthy volunteers. There were no significant side-effects and no adverse events attributable to tenoxicam. In this small study we have shown that tenoxicam administered preoperatively reduced the epidural analgesic requirements during the first 48 hours following major gynaecological surgery. There was no clinical or pathological evidence of haematological impairment following a single i.v. administration of tenoxicam 20 mg.

Aged↗

16 degrees C rapid temperature variation in central greenland 70,000 years Ago

Variations in the (29)N(2)/(28)N(2) ratio of air bubbles trapped in polar ice cores and their relation to variations of the (18)O/(16)O of the ice allow past surface temperature variations and ice age-gas age differences to be determined. High-resolution measurements of (29)N(2)/(28)N(2) in Dansgaard-Oeschger event 19 (around 70,000 years before the present) in ice from Central Greenland show that at the beginning of the event, the ice age-gas age difference was 1090 +/- 100 years. With the use of a combined firn densification, temperature, and gas diffusion model, the delta(18)O(ice)-temperature coefficient alpha was determined to be 0. 42 +/- 0.05 per mil per kelvin. This coefficient implies a mean surface temperature change of 16.0 kelvin (between 14.3 and 18.1 kelvin), which differs substantially from values derived from borehole temperatures and modern spatial delta(18)O(ice)-surface temperature correlations.

Journal Article↗

Daily sunscreen application and betacarotene supplementation in prevention of basal-cell and squamous-cell carcinomas of the skin: a randomised controlled trial.

BACKGROUND: The use of sunscreens on the skin can prevent sunburn but whether long-term use can prevent skin cancer is not known. Also, there is evidence that oral betacarotene supplementation lowers skin-cancer rates in animals, but there is limited evidence of its effect in human beings. METHODS: In a community-based randomised trial with a 2 by 2 factorial design, individuals were assigned to four treatment groups: daily application of a sun protection factor 15-plus sunscreen to the head, neck, arms, and hands, and betacarotene supplementation (30 mg per day); sunscreen plus placebo tablets; betacarotene only; or placebo only. Participants were 1621 residents of Nambour in southeast Queensland, Australia. The endpoints after 4.5 years of follow-up were the incidence of basal-cell and squamous-cell carcinomas both in terms of people treated for newly diagnosed disease and in terms of the numbers of tumours that occurred. Analysis of the effect of sunscreen was based only on skin cancers that developed on sites of daily application. All analyses were by intention to treat. FINDINGS: 1383 participants underwent full skin examination by a dermatologist in the follow-up period. 250 of them developed 758 new skin cancers during the follow-up period. There were no significant differences in the incidence of first new skin cancers between groups randomly assigned daily sunscreen and no daily sunscreen (basal-cell carcinoma 2588 vs 2509 per 100,000; rate ratio 1.03 [95% CI 0.73-1.46]; squamous-cell carcinoma 876 vs 996 per 100,000; rate ratio 0.88 [0.50-1.56]). Similarly, there was no significant difference between the betacarotene and placebo groups in incidence of either cancer (basal-cell carcinoma 3954 vs 3806 per 100,000; 1.04 [0.73-1.27]; squamous-cell carcinoma 1508 vs 1146 per 100,000; 1.35 [0.84-2.19]). In terms of the number of tumours, there was no effect on incidence of basal-cell carcinoma by sunscreen use or by betacarotene but the incidence of squamous-cell carcinoma was significantly lower in the sunscreen group than in the no daily sunscreen group (1115 vs 1832 per 100,000; 0.61 [0.46-0.81]). INTERPRETATION: There was no harmful effect of daily use of sunscreen in this medium-term study. Cutaneous squamous-cell carcinoma, but not basal-cell carcinoma seems to be amenable to prevention through the routine use of sunscreen by adults for 4.5 years. There was no beneficial or harmful effect on the rates of either type of skin cancer, as a result of betacarotene supplementation.

Adult↗

Enhanced sterol-acyl transferase activity promotes sterol accumulation in Saccharomyces cerevisiae.

The sterol-acyl transferase encoded by the gene ARE2 was transcriptionally deregulated in the yeast Saccharomyces cerevisiae to understand its role in sterol storage and sterol enrichment. Our results show that sterols can indeed be enriched in yeast by enhancing the capacity of the cells to esterify sterols. ARE2 overexpression had no impact on the accumulation of the early sterols such as lanosterol, but influenced the later intermediates and the end product ergosterol. Thus an enhanced conversion of free sterols to their esterified counterparts may provide a tool to increase the overall sterol content of the yeast cell. We have previously shown that the overexpression of a truncated version of the key enzyme of the early sterol pathway, HMG-CoA reductase (HMG1), leads to an increase in the early sterols such as lanosterol and zymosterol. The simultaneous deregulation of both genes in one strain produces a cumulative effect in that both early and late sterols are enhanced. Karmellae-like structures can be detected when Are2p is overexpressed. Are2p therefore constitutes a new member of the karmellae-inducing protein family.

Acyltransferases↗

A quantitative immunohistochemical study on the time-dependent course of acute inflammatory cellular response to human brain injury.

The time-dependent inflammatory cell reaction in human cortical contusions has been investigated during the first 30 weeks after blunt head injury. Immunohistochemical staining was carried out using CD 15 for granulocytes and LCA, CD 3 and UCHL-1 for mononuclear leucocytes. In order to provide reliable data for a forensic wound age estimation, the intensity of the cellular reaction was evaluated with a quantitative image analysis system. CD 15-labelled granulocytes were detectable earliest 10 min after brain injury, whereas significantly increased numbers of mononuclear leucocytes occurred in cortical contusions after a postinfliction interval of at least 1.1 days (LCA), 2 days (CD 3) or 3.7 days (UCHL-1), respectively.

Adolescent↗

Interspecies complementation in Saccharopolyspora erythraea : elucidation of the function of oleP1, oleG1 and oleG2 from the oleandomycin biosynthetic gene cluster of Streptomyces antibioticus and generation of new erythromycin derivatives.

Two glycosyltransferase genes, oleG1 and oleG2, and a putative isomerase gene, oleP1, have previously been identified in the oleandomycin biosynthetic gene cluster of Streptomyces antibioticus. In order to identify which of these two glycosyltransferases encodes the desosaminyltransferase and which the oleandrosyltransferase, interspecies complementation has been carried out, using two mutant strains of Saccharopolyspora erythraea, one strain carrying an internal deletion in the eryCIII (desosaminyltransferase) gene and the other an internal deletion in the eryBV (mycarosyltransferase) gene. Expression of the oleG1 gene in the eryCIII deletion mutant restored the production of erythromycin A (although at a low level), demonstrating that oleG1 encodes the desosaminyltransferase required for the biosynthesis of oleandomycin and indicating that, as in erythromycin biosynthesis, the neutral sugar is transferred before the aminosugar onto the macrocyclic ring. Significantly, when an intact oleG2 gene (presumed to encode the oleandrosyltransferase) was expressed in the eryBV deletion mutant, antibiotic activity was also restored and, in addition to erythromycin A, new bioactive compounds were produced with a good yield. The neutral sugar residue present in these compounds was identified as L-rhamnose attached at position C-3 of an erythronolide B or a 6-deoxyerythronolide B lactone ring, thus indicating a relaxed specificity of the oleandrosyltransferase, OleG2, for both the activated sugar and the macrolactone substrate. The oleP1 gene located immediately upstream of oleG1 was likewise introduced into an eryCII deletion mutant of Sac. erythraea, and production of erythromycin A was again restored, demonstrating that the function of OleP1 is identical to that of EryCII in the biosynthesis of dTDP-D-desosamine, which we have previously proposed to be a dTDP-4-keto-6-deoxy-D-glucose 3, 4-isomerase.

Chromatography, High Pressure Liquid↗

Rapid transbilayer movement of fluorescent phospholipid analogues in the plasma membrane of endocytosis-deficient yeast cells does not require the Drs2 protein.

Evidence is presented that endocytosis-deficient Saccharomyces cerevisiae end4 yeast cells rapidly internalize the fluorescent phospholipid analogues 1-palmitoyl-2-{6-[7-nitro-2,1, 3-benzoxadiazol-4-yl(NBD)amino] caproyl}phosphatidylcholine (P-C6-NBD-PtdCho) and P-C6-NBD-phosphatidylserine (P-C6-NBD-PtdSer). Both analogues redistributed between the exoplasmic and cytoplasmic leaflet with a half-time of < 15 min at 0 degrees C. The plateau of internalized analogues was about 70%. Transbilayer movement is probably protein-mediated, as the flip-flop of both analogues was very slow in liposomes composed of plasma-membrane lipids. Rapid analogue internalization was not abolished on depletion of intracellular ATP by about 90%. For P-C6-NBD-PtdCho only was a moderate decrease in the plateau of internalized analogues of about 20% observed, while that of P-C6-NBD-PtdSer was not affected. The Drs2 protein plays only a minor role, if any, in the rapid transbilayer movement of analogues in S. cerevisiae end4 cells. In S. cerevisiae end4 Deltadrs2 cells harbouring both an end4 allele and a drs2 null allele, about 60% and 50% of P-C6-NBD-PtdCho and P-C6-NBD-PtdSer, respectively, became internalized within 15 min at 0 degrees C. The preferential orientation of P-C6-NBD-PtdSer to the cytoplasmic leaflet is in qualitative agreement with the sequestering of endogenous phosphatidylserine to the cytoplasmic leaflet, as assessed by binding of annexin V. Virtually no binding of annexin V to spheroplasts of the parent wild-type strain or the mutant strains was observed. Likewise, no difference in the exposure of endogenous aminophospholipids to the exoplasmic leaflet between these strains was found by labelling with trinitrobenzenesulfonic acid. Thus, lipid asymmetry, at least of aminophospholipids, was preserved in S. cerevisiae end4 cells independently of the presence of the Drs2 protein.

4-Chloro-7-nitrobenzofurazan↗