Biomedical subjects

K Lorenz

Publications and source records attributed to K Lorenz.

At least 19 recordsLinked to original sources

PubMed2001

Minimally invasive video-assisted parathyroidectomy: multiinstitutional study.

Unilateral and minimally invasive parathyroidectomies with endoscopic and video-assisted technique have been introduced. Most of these procedures utilize preoperative localization and intraoperative monitoring of parathyroid hormone. There are only a few reports on these procedures. The objective of this study was to evaluate video-assisted parathyroidectomy (MIVAP) for surgery in patients with primary hyperparathyroidism (pHPT). From February 1997 to June 1999 a series of 123 consecutive patients with pHPT at four surgical centers were evaluated. The patients' ages ranged from 18 to 77 years (median 50 years). Preoperatively, sestamibi scintigraphy and ultrasonography for localization were performed for all patients. Selection criteria for a MIVAP procedure excluded patients with negative localization, suspicion of multiglandular disease (MGD) or thyroid malignancy, a large thyroid mass, and prior surgery or irradiation to the neck. MIVAP was performed with a 1.5 cm suprasternal incision; the operation was then done through this incision with a 30 degree 5 mm endoscope and microsurgical instruments with brief CO2 insufflation for adenoma identification. We then proceeded with an open technique through the small incision under video-assistance. Intraoperative monitoring of intact parathyroid hormone (iPTH) assays was used in all patients. Among the 123 patients in whom MIVAP was attempted, the procedure was accomplished in 109 (89%). Conversion to conventional cervicotomy was required in 14 (11%) patients because of failed localization, failure of the iPTH level to fall appropriately, or technical problems. There was no persistent or recurrent HPT during the 3 to 12-month follow-up. Oral calcium replacement for symptomatic hypocalcemia postoperatively was given in 7 (6%) cases. A unilateral transient laryngeal nerve palsy, resolving within 6 months postoperatively, occurred in two (2%) patients. The median hospital stay was 1.5 days (range 0.5-5.0 days). This study showed the feasibility of MIVAP as an alternative surgical treatment for pHPT in a selected group of patients. Further studies are necessary to evaluate the efficacy and rationale of MIVAP compared to other techniques for parathyroidectomy in pHPT patients.

Adenoma↗

PubMed2001

Importance of early screening and prophylactic thyroidectomy in asymptomatic nonindex RET germline carriers.

Genetic testing for RET germline mutations affords rapid identification of germline carriers, offering the prospect of cure before C-cell hyperplasia (CCH) has progressed to medullary thyroid carcinoma (MTC). Although nonindex RET mutation carriers have a better prognosis than do the index patients, it remains to be ascertained whether age represents a risk factor for MTC when screening patients. The current institutional study (October 1994 through June 1999) was set up to compare asymptomatic nonindex patients who were grouped by age: < 20 years and > or = 20 years. Inclusion criteria were confirmed RET mutations in the germline, with no MTC being more advanced than pT1pN1M0. Adult patients (> or = 20 years) had MTC significantly more often (84% vs. 43%), significantly larger tumors (5 mm vs. 3 mm), and significantly higher basal calcitonin levels preoperatively (78.0 vs. 9.7 pg/ml) than their pediatric/adolescent counterparts (< 20 years). There was a close correlation between pT1 MTC and an elevated basal serum calcitonin level (r = 0.67; Spearman's rho). All three patients with lymph node metastases from MTC had elevated basal calcitonin levels. The two groups did not differ in terms of multifocality of MTC (pT1b), lymph node involvement (pN1) or bilateral lymph node metastasis (pN1b), or preoperative stimulated and postoperative basal and stimulated serum calcitonin. Prophylactic thyroidectomy should not be postponed beyond the age of 20, and it should be performed before basal serum calcitonin has turned positive. Pathologic conversion of stimulated serum calcitonin obviously marks the time in carriers of RET germline mutations when surgery should be scheduled at the latest to be prophylactic.

Adolescent↗

PubMed2000

Dendrimers: relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of 125I-labelled polyamidoamine dendrimers in vivo.

Dendrimers are highly branched macromolecules of low polydispersity that provide many exciting opportunities for design of novel drug-carriers, gene delivery systems and imaging agents. They hold promise in tissue targeting applications, controlled drug release and moreover, their interesting nanoscopic architecture might allow easier passage across biological barriers by transcytosis. However, from the vast array of structures currently emerging from synthetic chemistry it is essential to design molecules that have real potential for in vivo biological use. Here, polyamidoamine (PAMAM, Starburst), poly(propyleneimine) with either diaminobutane or diaminoethane as core, and poly(ethylene oxide) (PEO) grafted carbosilane (CSi-PEO) dendrimers were used to study systematically the effect of dendrimer generation and surface functionality on biological properties in vitro. Generally, dendrimers bearing -NH(2) termini displayed concentration- and in the case of PAMAM dendrimers generation-dependent haemolysis, and changes in red cell morphology were observed after 1 h even at low concentrations (10 microg/ml). At concentrations below 1 mg/ml CSi-PEO dendrimers and those dendrimers with carboxylate (COONa) terminal groups were neither haemolytic nor cytotoxic towards a panel of cell lines in vitro. In general, cationic dendrimers were cytotoxic (72 h incubation), displaying IC(50) values=50-300 microg/ml dependent on dendrimer-type, cell-type and generation. Preliminary studies with polyether dendrimers prepared by the convergent route showed that dendrimers with carboxylate and malonate surfaces were not haemolytic at 1 h, but after 24 h, unlike anionic PAMAM dendrimers they were lytic. Cationic 125I-labelled PAMAM dendrimers (gen 3 and 4) administered intravenously (i.v.) to Wistar rats ( approximately 10 microg/ml) were cleared rapidly from the circulation (<2% recovered dose in blood at 1 h). Anionic PAMAM dendrimers (gen 2.5, 3.5 and 5.5) showed longer circulation times ( approximately 20-40% recovered dose in blood at 1 h) with generation-dependent clearance rates; lower generations circulated longer. For both anionic and cationic species blood levels at 1 h correlated with the extent of liver capture observed (30-90% recovered dose at 1 h). 125I-Labelled PAMAM dendrimers injected intraperitoneally were transferred to the bloodstream within an hour and their subsequent biodistribution mirrored that seen following i.v. injection. Inherent toxicity would suggest it unlikely that higher generation cationic dendrimers will be suitable for parenteral administration, especially if they are to be used at a high dose. In addition it is clear that dendrimer structure must also be carefully tailored to avoid rapid hepatic uptake if targeting elsewhere (e.g. tumour targeting) is a primary objective.

Animals↗

PubMed2000

Axillary lymph nodes in breast cancer: is size related to metastatic involvement?

Usually when using imaging procedures, such as axillary mammography or ultrasonography, a cutoff level of 5 mm for lymph node size is postulated to be not only the limit of lymph node visibility but also a sign of metastatic involvement. The aim of this study was to evaluate whether this assumption, used as a basic hypothesis in many reports, is true. A series of 72 axillary specimens from 71 breast carcinoma patients operated at the university hospital of Vienna were analyzed. A comparison of histologically noninvolved axillary specimens with those showing metastatic involvement revealed that the two groups did not differ significantly according to the number or size of lymph nodes per axilla. For lymph nodes <5 mm the probability of being metastatically involved was still 10%. Enlarged lymph nodes (5-20 mm) had a slightly higher risk of being malignant (20%). In contrast, the probability of metastatic involvement for lymph nodes >20 mm was only 40%. We suggest that many reports dealing with the prediction of malignancy in axillary lymph nodes may have used misleading basic assumptions, so the results of these studies must be viewed critically.

Axilla↗

PubMed2000

Unilateral open and minimally invasive procedures for primary hyperparathyroidism: a review of selective approaches.

The currently established procedure for surgical treatment of primary hyperparathyroidism is bilateral exploration and visualization of all four glands to identify an adenoma and exclude multiglandular disease. With the development of improved preoperative localization imaging of the parathyroids using high-resolution ultrasonography and sestamibi scintigraphy, on the one hand, and perioperative control of surgical success with a rapid parathyroid hormone assay on the other, unilateral and minimally invasive techniques have become feasible. For patients with unequivocal localization in preoperative sestamibi scintigraphy and high-resolution ultrasonography of the parathyroid adenoma in probable single-gland disease, the unilateral and minimally invasive parathyroidectomy present a therapeutic option. Perioperative rapid parathyroid hormone assays, although costly, offer immediate supervision of adenoma extirpation and differentiation of single- and multiglandular disease. These methods demonstrate advantages with favorable cosmetic results and lower reported rate of postoperative hypoparathyroidism. These methods are already being practiced in some places under local anesthesia and in an ambulatory setting. This contribution provides an introduction and overview of the currently practiced unilateral and minimally invasive techniques of parathyroidectomy for primary hyperparathyroidism, discussing indications, advantages and disadvantages, and technical differences in the practiced methods.

Humans↗

PubMed2000

Chlorpromazine modulates cytokine expression in the liver and lung after burn injury and endotoxemia.

BACKGROUND: Previous data from our laboratory have demonstrated that alterations in cytokine production occur in the lung and liver as the result of a two-hit model of injury, i.e., burn with subsequent endotoxin administration. The purpose of this study was to determine whether the phenothiazine derivative chlorpromazine would alter cytokine production in a sequential model of injury. METHODS: By using a sublethal burn/endotoxemia model, B2D6F1 mice (n = 40) were assigned to two groups and subjected to a 15% full-thickness burn. Three days after burn injury, one group (BURN/ETX) received 2.5 mg/kg Escherichia coli endotoxin intraperitoneally, and the other group (CPZ) received 4 mg/kg chlorpromazine 1 hour before the administration of 2.5 mg/kg E. coli endotoxin intraperitoneally. At selected time points, the animals were killed and lung and liver were removed and processed for protein and total RNA. Northern blots and enzyme-linked immunosorbent assays were used to assess the production of tumor necrosis factor-alpha, macrophage inflammatory protein-1alpha, and interleukin-10. RESULTS: Chlorpromazine significantly reduced tumor necrosis factor-alpha mRNA and protein expression in the liver. Macrophage inflammatory protein-1alpha mRNA was reduced by chlorpromazine in both liver and lung. Interleukin-10 production was not altered by chlorpromazine. CONCLUSION: The reduction of tumor necrosis factor-alpha and macrophage inflammatory protein-1alpha by chlorpromazine in the liver and lungs may have potential as a pharmaceutical agent that may dampen the inflammatory response in a model of sequential injury.

Animals↗

PubMed2000

Differential regulation of two thiolase genes from Clostridium acetobutylicum DSM 792.

Thiolase of Clostridium acetobutylicum is an important enzyme involved in both, acid and solvent fermentation. Two thiolase genes (thlA and thIB) have been cloned and sequenced from Clostridium acetobutylicum DSM 792, showing high homology to each other and to thiolases of PHA-synthesizing bacteria. The thlA gene is identical to the gene already cloned and sequenced from strain ATCC 824 (Stim-Herndon et al., 1995, Gene 154: 81-85). Using primer extension and S1 nuclease analysis a transcriptional start site was identified 102 bp upstream of the thlA start codon. This site was preceded by a region that exhibits high similarity to the sigma70 consensus promoter sequences of Gram-positive and -negative bacteria. Regulation of thlA and thlB was studied at the transcriptional level to elucidate the specific function of each gene. Non-radioactive primer extension analysis using fluorescein-labelled oligonucleotides and Northern blot analysis revealed high levels of thlA transcripts in acid- and solvent-producing cells. During an induced shift of a continuous culture from acid to solvent formation, the transcript level transiently decreased to a minimum, 3 to 7 h after induction. The thlA transcript length is about 1.4 kb, indicating a monocistronic organisation, whereas genetic organization and reverse transcription (RT)-PCR analysis indicated that thlB forms an operon with two other adjacent genes, thlR and thlC. Transcription and regulation of the thlB operon was studied using RTPCR and showed a very low expression in acid- and solvent-producing cells. Heterologously expressed clostridial ThlB showed high thiolase activity in Escherichia coli. The N-terminal part of ThlR possesses a potential helix-turn-helix motif and shows significant homology to regulatory proteins belonging to the TetR/AcrR family of transcriptional regulators. ThlR possibly acts as a transcriptional repressor of thlB operon expression. The data provide strong evidence that ThlA is involved in the metabolism of both acid and solvent formation, whereas the physiological function of ThlB has yet to be elucidated.

Acetyl-CoA C-Acetyltransferase↗

PubMed1999

The sharer.

Explore the source record for details and available documents.

Humans↗

PubMed1999

Minimally invasive video-assisted parathyroidectomy--selective approach to localized single gland adenoma.

BACKGROUND: The valid operative standard for primary hyperparathyroidism (pHPT) consists of cervicotomy and presentation of all parathyroid glands. This operative technique features the macroscopic identification of the responsible adenoma. It also has the advantage of detecting multiglandular disease. The increasing sensitivity of preoperative localization methods and the possibility of intra-operative measurement of parathyroid hormone prepared the way for minimally invasive procedures. METHODS: All patients with pHPT were examined by cervical sonography and sestamibi scintigraphy of the parathyroid glands. Patients eligible for the described procedure had to comply to the following inclusion criteria: biochemical evidence of pHPT, localization of one unequivocally enlarged parathyroid gland on two corresponding imaging results; no former surgery or radiation to the neck; no multinodular goiter; no suspected carcinoma of the thyroid; and no secondary or recurrent hyperparathyroidism. We used an operative technique first described by Miccoli in 1997. Before preparation and at 2, 10 and 15 min after exstirpation of the parathyroid adenoma, peripheral blood was drawn. The operation was terminated when a 50% decrease of preoperative PTH levels was reached. RESULTS: During a 12-month period (1 December 1997 to 30 November 1998), 13 patients with pHPT of a total of 59 patients (22%) with hyperparathyroidism (pHPT and sHPT) were operated on employing this minimally invasive procedure. In three patients, the operative technique had to be converted to the conventional procedure due to superior adenomas in two cases and a dorsoesophageal adenoma in one case. The procedure could thus be successfully completed in ten patients. The overall failure rate was zero in all patients with regard to the underlying disease. There was one temporary, recurrent laryngeal-nerve palsy. The mean overall length of the hospital stay was 3 days. CONCLUSION: The minimally invasive video-assisted parathyroidectomy for localized single-gland adenoma is a new and attractive surgical therapy option for primary hyperparathyroidism due to improved patient comfort, shortened length of hospital stay and favorable cosmetic results. This may lead to one-day surgery and, therefore, to a reduction of overall costs.

Adenoma↗

PubMed1999

[Surgery for hyperthyroidism].

The concept of therapy for hyperthyroidism combines endocrinology, nuclear medicine and surgery. For selection of the treatment of choice, pathophysiology as well as individual aspects are considered. Surgical therapy is mainly concerned with treatment of functional autonomy, Grave's disease and iodine-excess-related hyperthyroidism based on either autonomous or Grave's disease. For each of these three main groups of hyperthyroidism exist differentiated surgical concepts based on the underlying thyroid disease and its course: The various forms of functional autonomy, solitary autonomous nodules, multifocal autonomy or disseminated autonomy are dealt with selective enucleation-resection, functionally and morphologically oriented resection and extensive resection with little remaining thyroid tissue of about 5-6 ml, respectively. For Grave's disease extensive resections with thyroid-tissue remainders of about 2-4 ml or tatal thyroidectomy are established; the latter demonstrating in cases of concomittant endocrine ophthalmopathy the most convincing results. In cases of iodine-related hyperthyroidism the concept of early and radical surgical treatment, following stabilization of the patient in a reasonably short amount of time shows best results and is thus favored. In these cases, contrary to all other forms of hyperthyroidism, establishment of preoperative euthyroid metabolism is not mandatory.

Humans↗

PubMed1999

Diagnostic strategies and surgical procedures in persistent or recurrent primary hyperparathyroidism.

The incidence of persistent or recurrent primary hyperparathyroidism reported in the literature lies between 1 and 10%. The main causes are represented by atypical locations or incorrect diagnosis of primary parathyroid hyperplasia. Since primary parathyroidectomy by an experienced surgeon has a success rate of 95%, there is no need for extended imaging studies prior to initial bilateral exploration. After confirming diagnosis of persistent or recurrent hyperparathyroidism exact localization studies are necessary. The most important procedures are ultrasonography, magnetic resonance imaging, technetium Tc99m sestamibi scintigraphy with a combined sensitivity of approximately 90%. In case of negative imaging results selective venous catheterization before reoperation can be performed. Reoperation by an experienced surgeon will be successful in 95% of cases.

Diagnostic Imaging↗

PubMed1999

Concept of and preliminary trial protocol for adjuvant treatment of mediastinitis with immunoglobulins after cardiac surgery (ATMI): response to comments and criticism.

During the consensus-based process of protocol development external experts were invited to comment on a proposal for a trial protocol on adjuvant immunotreatment of patients with wound infection after median sternotomy (ATMI). Controversies and arguments can be divided into five main areas: 1) rationale and objectives; 2) criteria for patient selection; 3) adjuvant treatment; 4) measures of efficacy; and 5) course and timetable of the study. We present and summarise the experts comments and criticism as well as the result of the final discussion of the study group with respect to these areas.

APACHE↗

PubMed1999

[Surgical treatment of Graves' disease].

In the surgical treatment of Graves' disease, there are several concepts established. The methods of bilateral subtotal resection, hemithyreoidectomy combined with contralateral subtotal resection, near-total resection and total thyreoidectomy all have there rightful placement in the surgical treatment of Graves' disease. The method of choice should be selected according to the activity of the disease. To avoid a recurrence of the disease, the more aggressive resections have proven to be more successful and there's evidence of preference of these techniques lately. Despite the more refined surgical techniques, the radical resections are still burdened with higher complication rates, specifically recurrent nerve palsy and hypoparathyroidism. Due to the excellent long lasting results of total thyreoidectomy, this concept appears to be the most convincing when technically well administered as it reliably cures the disease. The further development and regular use of technical aid such as surgical magnification lenses and neuromonitoring are expected to eventually help improve the more radical surgical concepts in the future. The prospect of combining surgical therapy with radioiodine-therapy may represent a chance to cure Graves' disease effectively and minimize complications from different sides.

Graves Disease↗

PubMed1998

Substituted 4-acylpyrazoles and 4-acylpyrazolones: synthesis and multidrug resistance-modulating activity.

A series of 4-acyl-3-pyrazolone derivatives with a 3-substituted 2-hydroxy-3-aminopropyl chain attached to pyrazole N-1 (7-20) as well as isomeric 4-acyl-5-(3-substituted 3-amino-2-hydroxypropoxy)pyrazole derivatives (5, 6) were synthesized, and their multidrug resistance (MDR)-modulating activity was measured using the daunomycin efflux assay. Reaction of N1-substituted 4-acyl-3-pyrazolones (tautomer to 4-acyl-5-hydroxypyrazoles) with excessive epichlorohydrin and successive treatment with an appropriate amine resulted in N-alkylation and thus afforded the target pyrazolone derivatives 7-20. In contrast, O-alkylation occurred upon reaction with 1 equiv of epichlorohydrin and subsequent treatment with amine leading to the corresponding 4-acyl-5-pyrazolyl ethers 5 and 6. QSAR studies showed a good correlation of MDR-modulating activity with lipophilicity of the compounds. Inclusion of hydrogen bond acceptor strength and steric parameters as descriptors led to a QSAR equation with remarkably increased predictive power (r2cv = 0.92). Additionally, ortho substitution of the propanolamine side chain and the acyl moiety is favorable. Detailed NMR spectroscopic investigations were carried out with the title compounds.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1997

Down-regulation of tissue specific tumor necrosis factor-alpha in the liver and lung after burn injury and endotoxemia.

Burn injury and endotoxin lead to the development of a systemic inflammatory response. Because tumor necrosis factor-alpha (TNF-alpha) is a component of the proinflammatory response, we have determined the effect of burn injury and endotoxin in a murine model of thermal on tissue specific TNF-alpha levels in the liver and lung. Male mice were divided into four groups and injected with endotoxin (ETX) (2.5 mg/kg intraperitoneally) or saline (CNTL) or subjected to a 16% full-thickness scald burn (B), or ETX administration 72 hours after burn injury (B+ETX). Animals were killed at 0 to 24 hours after ETX or CNTL, 0 to 72 hours after B, and 72 to 96 hours after B+ETX (ETX administration 72 hours after B). TNF-alpha mRNA by Northern blot and protein analysis by enzyme-linked immunosorbent assay were determined and protein expressed as nanogram per gram of tissue. Statistical analysis was performed using analysis of variance with significance at p < 0.05. Burn injury did not result in detectable levels of liver or lung TNF protein or mRNA. Endotoxin administration resulted in a near six-fold rise in liver TNF protein compared with controls at 1, 2, and 6 hours after ETX (p < 0.05 to p < 0.001). Liver mRNA remained elevated from 20 minutes to 24 hours after ETX versus CNTL (p < 0.05). Endotoxin injection produced a persistent lung TNF protein elevation reaching significance at 1 and 2 hours (p < 0.001) and a rise in mRNA at 40 minutes to 6 hours (p < 0.05) versus CNTL. The liver showed a trend of reduced mRNA after B+ETX versus ETX (p = NS), whereas protein levels were reduced by 50 to 60% at 1 and 2 hours (p < 0.01). Lung mRNA values after B+ETX were only 40% compared with ETX at nearly all time points (p < 0.001) but were 15 times above CNTL values at 2 hours (p < 0.05). Based on these results, we conclude that burn injury did not cause an increase in liver or lung tissue specific TNF-alpha. However, the presence of a preexisting burn injury dramatically altered the response to endotoxin and the primary point of regulation appears to be at the posttranscriptional level.

Animals↗

PubMed1995

Structural organization and differential expression of carrot beta-fructofuranosidase genes: identification of a gene coding for a flower bud-specific isozyme.

Three genomic clones (Inv*Dc1, Inv*Dc2 and Inv*Dc3) were isolated by using the cDNA for carrot cell wall beta-fructofuranosidase as a probe. The expression patterns of the three genes differed markedly. High levels of Inv*Dc1 transcripts were found in leaves and roots of young carrot, whereas in plants with developing tap roots no transcripts were detected. A high level of mRNA of Inv*Dc1 was also present in suspension-cultured cells. In developing reproductive organs, only low levels of transcripts of Inv*Dc1 were found in flower buds and flowers and none at later stages of development. In contrast, Inv*Dc2 and Inv*Dc3 were not expressed in vegetative plant organs. Invb1*Dc1 was exclusively and strongly expressed in flower buds, and Inv*Dc3 at a very low level in suspension-cultured cells.

Amino Acid Sequence↗

PubMed1995

Insulin sensitization in diabetic rat liver by an antihyperglycemic agent.

This study aimed to demonstrate directly that the thiazolidinedione pioglitazone acts as an insulin sensitizer. We tested the hypothesis that pioglitazone treatment of diabetic rats alters liver function such that responsiveness of selected genes to subsequent insulin regulation is enhanced. Although flux through gluconeogenic/glycolytic pathways involves regulation of many enzymes, we presently report the effects of insulin on expression of two key enzymes in these metabolic pathways, ie, phosphoenolpyruvate carboxykinase (PEPCK) and glucokinase (GK). Rats were either studied as nondiabetic controls or injected with streptozotocin as a model for insulin-deficient diabetes. Diabetic animals were treated without or with pioglitazone and subsequently examined for acute responses to insulin. Pioglitazone treatment of diabetic animals significantly enhanced the effects of insulin to reverse elevated blood glucose. Although the mean level of liver mRNA transcripts encoding PEPCK was increased to nearly 300% in diabetic animals as compared with nondiabetic controls (100%), it was significantly lower in pioglitazone-treated diabetic rats (119% of control) than in diabetic rats without pioglitazone (223% of control) after insulin treatment. By contrast, mRNA transcripts encoding GK were not detectable in diabetic animals, but were increased markedly by insulin treatment in all animal groups. Insulin-enhanced expression of GK was significantly greater in liver from animals that were treated earlier with pioglitazone (291% of control) than in liver from those that were untreated (214% of control). An amplified acute response of liver to insulin thus established pioglitazone as an insulin sensitizer. Our findings further showed that such sensitization can be developed even in the insulin-deficient state.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Solventogenic enzymes of Clostridium acetobutylicum: catalytic properties, genetic organization, and transcriptional regulation.

The enzymes acetoacetate decarboxylase and coenzyme A transferase catalyse acetone production from acetoacetyl-CoA in Clostridium acetobutylicum. The adc gene encoding the former enzyme is organized in a monocistronic operon, while the ctf genes form a common transcription unit with the gene (adhE) encoding a probable polyfunctional aldehyde/alcohol dehydrogenase. This genetic arrangement could reflect physiological requirements at the onset of solventogenesis. In addition to AdhE, two butanol dehydrogenase isozymes and a thiolase are involved in butanol synthesis. RNA analyses showed a sequential order of induction for the different butanol dehydrogenase genes, indicating an in vivo function of BdhI in low level butanol formation. The physiological roles of AdhE and BdhII most likely involve high level butanol formation, with AdhE being responsible for the onset of solventogenesis and BdhII ensuring continued butanol production. Addition of methyl viologen results in artificially induced butanol synthesis which seems to be mediated by a still unknown set of enzymes. Although the signal that triggers the shift to solventogenesis has not yet been elucidated, recent investigations suggest a possible function of DNA supercoiling as a transcriptional sensor of the respective environmental stimuli.

Base Sequence↗