[Quality in acute inpatient rheumatology 2021 : Current aspects of the KOBRA quality label of the Association of Rheumatological Acute Care Clinics]. / Qualität in der akutstationären Rheumatologie 2021 : Aktuelle Aspekte zum KOBRA-Qualitätslabel des Verbandes Rheumatologischer Akutkliniken (VRA e.V.).

A comprehensive health policy quality campaign launched in 2021 aims to improve the quality and transparency of hospital care for people with diseases in Germany. Legal requirements for minimum volumes and the expansion of quality contracts between cost units and hospitals as well as the use of quality indicators relevant to planning for demand-oriented and quality-oriented further development of inpatient care will increase competition in the quality of care between hospitals. The topic of development and definition of quality in medicine was also comprehensively addressed by the Association of Rheumatological Acute Care Clinics (VRA) shortly after its foundation in 1998. At the center of acute inpatient quality management are binding structural criteria linked to the continuous outcome benchmarking in acute rheumatology care (KOBRA) project launched in 2003 in rheumatology (and continuously implemented to date) measuring process and outcome quality. Based on this framework (fulfillment of the structural quality and participation in the KOBRA project) successfully participating rheumatology units can acquire the KOBRA seal of approval for 2 years at a time, which is awarded by the project management, the aQua Institute. The outstanding position of the project is exemplified by data evaluation on treatment change in active rheumatoid arthritis, diagnosis confirmation of connective tissue diseases and vasculitis during the inpatient stay as well as on participatory decision-making processes concerning rheumatoid arthritis (referring to the results of the data collection period 2018). By anchoring projects for structural, process and outcome quality acute inpatient rheumatology is well prepared for the paradigm shift demanded by health policies. Additionally, the KOBRA project is a good prerequisite to meet the requirements concerning quality management fixed in the Federal Joint Committee (G-BA) guidelines for recognition as a rheumatology center.

[Future of acute inpatient rheumatology in Germany : Statement of the Boards of the German Society for Rheumatology and the Association of Rheumatological Acute Clinics on hospital planning North-Rhine/Westphalia 2019 for the discipline rheumatology]. / Zukunft der akutstationären Rheumatologie in Deutschland : Stellungnahme der DGRh- und VRA-Vorstände zur Krankenhausplanung NRW 2019 für den Leistungsbereich Rheumatologie.

In September 2019 the Ministry of Labor, Health and Welfare (MAGS) of North-Rhine/Westphalia (NRW) published an expert report on hospital planning. In this report a fundamental reform of hospital planning was recommended, in that a requirements planning should be carried out in the future on the basis of a detailed designation of disciplines and organizational groups. At the request of the MAGS NRW, the German Society for Rheumatology (DGRh) with the support of the Association of Rheumatological Acute Clinics (VRA) has also commented on this issue.

Prenatal prediction of postnatal large-for-dates neonates using a simplified MRI method: comparison with conventional 2D ultrasound estimates.

OBJECTIVE: To evaluate the performance of a simple semi-automated method for estimation of fetal weight (EFW) using magnetic resonance imaging (MRI) as compared with two-dimensional (2D) ultrasound (US) for the prediction of large-for-dates neonates. METHODS: Data of two groups of women with singleton pregnancy between March 2011 and May 2016 were retrieved from our database and evaluated retrospectively: the first group included women who underwent US-EFW and MRI-EFW within 48 h before delivery and the second group included women who had these evaluations between 35 + 0 weeks and 37 + 6 weeks of gestation, more than 48 h before delivery. US-EFW was based on Hadlock et al. and MRI-EFW on the formula described by Baker et al. For MRI-EFW, planimetric measurement of the fetal body volume (FBV) was performed using a semi-automated method and the time required for measurement was noted. Outcome measure was the performance of MRI-EFW vs US-EFW in the prediction of large-for-dates neonates, both ≤ 48 h and > 48 h before delivery. Receiver-operating characteristics (ROC) curves for each method were compared using the DeLong method. RESULTS: Of the 270 women included in the first group, 48 (17.8%) newborns had birth weight ≥ 90th centile and 30 (11.1%) ≥ 95th centile. The second group included 83 women, and nine (10.8%) newborns had birth weight ≥ 95th centile. Median time needed for FBV planimetric measurements in all 353 fetuses was 3.5 (range, 1.5-5.5) min. The area under the ROC curve (AUC) for prediction of large-for-dates neonates by prenatal MRI performed within 48 h before delivery was significantly higher than that by US (for birth weight ≥ 90th centile, difference between AUCs = 0.085, standard error (SE) = 0.020, P < 0.001; for birth weight ≥ 95th centile, difference between AUCs = 0.036, SE = 0.014, P = 0.01). Similarly, MRI-EFW was better than US-EFW in predicting birth weight ≥ 95th centile when both examinations were performed > 48 h prior to delivery (difference between AUCs = 0.077, SE = 0.039, P = 0.045). CONCLUSION: MRI planimetry using our purpose-designed semi-automated method is not time-consuming. The predictive performance of MRI-EFW performed immediately prior to or remote from delivery is significantly better than that of US-EFW for the prediction of large-for-dates neonates. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Limiting mechanisms of force production after repetitive dynamic contractions in human triceps surae.

The influence of repetitive dynamic fatiguing contractions on the neuromuscular characteristics of the human triceps surae was investigated in 10 subjects. The load was 50% of the torque produced during a maximal voluntary contraction, and the exercise ended when the ankle range of motion declined to 50% of control. The maximal torque of the triceps surae and the electromyographic (EMG) activities of the soleus and medial gastrocnemius were studied in response to voluntary and electrically induced contractions before and after the fatiguing task and after 5 min of recovery. Reflex activities were also tested by recording the Hoffmann reflex (H reflex) and tendon reflex (T reflex) in the soleus muscle. The results indicated that whereas the maximal voluntary contraction torque, tested in isometric conditions, was reduced to a greater extent (P < 0.05) at 20 degrees of plantar flexion (-33%) compared with the neutral position (-23%) of the ankle joint, the EMG activity of both muscles was not significantly reduced after fatigue. Muscle activation, tested by the interpolated-twitch method or the ratio of the voluntary EMG to the amplitude of the muscle action potential (M-wave), as well as the neuromuscular transmission and sarcolemmal excitation, tested by the M-wave amplitude, did not change significantly after the fatiguing exercise. Although the H and T reflexes declined slightly (10-13%; P < 0.05) after fatigue, these adjustments did not appear to have a direct deleterious effect on muscle activation. In contrast, alterations in the mechanical twitch time course and postactivation potentiation indicated that intracellular Ca(2+)-controlled excitation-contraction coupling processes most likely played a major role in the force decrease after dynamic fatiguing contractions performed for short duration.

Recombinant mouse-human chimeric antibodies as calibrators in immunoassays that measure antibodies to Toxoplasma gondii.

In the present study, we examined the feasibility of using recombinant antibodies containing murine variable regions and human constant regions as calibrators or controls in immunoassays. As a model system, we chose the Abbott IMx Toxo immunoglobulin M (IgM) and Toxo IgG assays designed to detect antibodies to Toxoplasma gondii. Two mouse monoclonal antibodies were selected based on their reactivity to the T. gondii antigens P30 and P66. Heavy- and light-chain variable-region genes were cloned from both hybridomas and transferred into immunoglobulin expression vectors containing human kappa and IgG1 or IgM constant regions. The constructs were stably transfected into Sp2/0-Ag14 cells. In the IMx Toxo IgG assay, immunoreactivity of the anti-P30 chimeric IgG1 antibody paralleled that of the positive human plasma-derived assay calibrators. Signal generated with the anti-P66 chimeric IgG1 antibody was observed to plateau below the maximal reactivity observed for the assay calibrator. Examination of the IgM chimeric antibodies in the IMx Toxo IgM assay revealed that both the anti-P30 and anti-P66 antibodies matched the assay index calibrator manufactured with human Toxo IgM-positive plasma. When evaluated with patient samples, the correlation between results obtained with the chimeric antibody calibrators and the positive human plasma calibrators was > or =0.985. These data demonstrate that chimeric mouse-human antibodies are a viable alternative to high-titer positive human plasma for the manufacture of calibrators and controls for diagnostic assays.

[Renal hemodynamics and proteinuria in chronic glomerulonephritis treated with beta-receptor blockers or ace inhibitors]. / Renale Hämodynamik und Proteinurie bei chronischer Glomerulonephritis unter Behandlung mit beta-Rezeptorenblockern oder ACE-Hemmern.

BACKGROUND AND OBJECTIVE: In patients with chronic glomerular nephropathy associated arterial hypertension and proteinuria are considered to be cardinal risk factors in the progressive deterioration of renal function. Treatment regimens which reduce proteinuria and hypertension improve prognosis. The effect of the new beta-receptor blockers compared to common ACE-Inhibitors is of special interest. PATIENTS AND METHODS: The studied cohort consisted of 11 patients with CGN, hypertension and proteinuria > 400 mg/24 h. Four drugs were given for 4 weeks, doubly blinded and randomized according to a "Latin-square design": Celiprolol (beta-1-antagonist, beta-2-agonist, 200 mg/d), Atenolol (selective beta-1-antagonist, 50 mg/d), Ramipril (ACE-inhibitor, 2.5 mg/d) and placebo. There was a two-week wash-out phase between each of the four treatment phases. At the end of each treatment phase glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin and para-amino-hippuric acid (PAH) clearance. Proteinuria was determined in the course of a three-day collection period at the end of each treatment phase. During this period blood pressures were measured with a continuous 24-hour blood pressure monitor. RESULTS: Mean arterial blood pressure (MAP) was significantly reduced, compared with placebo, by all three antihypertensives (108 +/- 9 mm Hg with placebo, 98 +/- 12 mg Hg with atenolol, 101 +/- 11 mm Hg with celiprolol and 98 +/- 8 mm Hg with ramipril; P < 0.01). Celiprolol produced a significant rise In ERPF (322 +/- 109 ml/min with placebo, 391 +/- 110 ml/min with celiprolol: P < 0.05). GFR was slightly, but not significantly, reduced by celiprolol and atenolol. Filtration fraction remained unchanged with atenolol and celiprolol, while it was slightly, but not significantly, reduced with ramipril. Compared with the placebo, all three drugs significantly reduced proteinuria (P < 0.05): 1.8 +/- 1.3 g/24 h with placebo, 1.2 +/- 1.2 g/24 h with atenolol, 1.2 +/- 1.1 g/24 h with celiprolol and 1.4 +/- 1.4 g/24 h with ramipril. CONCLUSION: These data indicate that, in addition to ACE inhibitors, the new generation of beta-receptor blockers in particular, because of their vasodilator action, favourably influence proteinuria and renal blood flow in patients with CGN and arterial hypertension.

Randomized controlled trial of ACE-inhibitors and beta-blockers with and without vasodilating activity in chronic glomerulonephritis.

A prospective double-blind, randomized study was conducted to compare the effects of the beta 1 antagonist, beta 2 agonist celiprolol (200 mg daily) on renal hemodynamics and protein excretion with those of the beta 1 antagonist atenolol (50 mg daily), the ACE-inhibitor ramipril (2.5 mg daily), and placebo in 11 patients with proteinuria > 400 mg/24 h due to chronic glomerulonephritis. All 4 substances were given in a double-blind, randomized manner according to a latin-square design over a period of 4 weeks with a wash-out period of 2 weeks in between. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin and PAH clearance. Proteinuria was assessed by urine sampling at the end of each treatment period. Mean arterial pressure (MAP) was reduced significantly (p < 0.01) by all 3 drugs compared to placebo (108 +/- 9 mmHg placebo, 98 +/- 12 mmHg atenolol, 101 +/- 11 mmHg celiprolol, and 98 +/- 8 mmHg ramipril). Celiprolol induced a significant increase in ERPF compared to placebo (322 +/- 109 ml/min under placebo versus 391 +/- 110 ml/min under celiprolol, p < 0.05). GFR was slightly but insignificantly increased under atenolol and celiprolol. Filtration fraction (FF) remained unchanged in case of atenolol and celiprolol treatment and was slightly but not significantly reduced by ramipril. Proteinuria was significantly (p < 0.05) reduced compared to placebo by all 3 drugs (1.8 +/- 1.3 g/24 h under placebo, 1.2 +/- 1.2 g/24 h under atenolol, 1.2 +/- 1.1 g/24 h under celiprolol, and 1.4 +/- 1.4 g/24 h under ramipril). These data demonstrate that new beta-blocking agents show favorable effects on proteinuria and renal blood flow in patients with chronic glomerulonephritis and arterial hypertension. This may be attributed to their vasodilating properties.

[Humoral immune response to retinal S-antigen in patients with uveitis]. / Humorale Immunantwort gegen retinales S-Antigen bei Patienten mit Uveitis.

Experimental autoimmune uveoretinitis (EAU) is a predominantly T-cell-mediated autoimmune inflammatory disease of the retina and uveal tract of the eye. Retinal S-antigen, a protein found in retinal photoreceptor cells, is a potent agent for the induction of EAU in susceptible species and strains. Elevated titers of antibody to S-antigen have been reported in patients with different forms of uveitis. Serum samples from 166 patients and 87 healthy blood donors were tested by immunoblotting against human retinal abstract for IgG, IgM and IgA antibodies to S-antigen. Compared to the controls the patient sera showed a higher incidence of S-specific antibodies (17.5% vs 9.2%). No specific correlation between the presence of any type of uveitis and anti-S antibodies has been found (anterior uveitis 15.1%, posterior 19.6%, panuveitis 18.9%). There was a higher incidence especially with IgG antibodies during active disease (19.7% vs 9.2% in controls). The results suggest that since EAU is T-cell mediated, antibodies in humans may be most important as indicators of autoimmunity rather than mediators of the inflammation. As these anti-S antibodies might be induced by disruption and nonspecific inflammation of the retina and uvea alone, an important and difficult question in patients is whether or not these secondary autoimmune response can contribute to the induction of uveitis.

Antigens produced by recombinant DNA technology.

Some of the greatest beneficiaries of the revolutionary advances in biotechnology over the past 15 years have been producers of diagnostic reagents, especially for the cloning and expression of antigens, primarily of viral origin. Recombinant DNA technology provides methods for producing antigens for diagnostic assays that are more highly purified, more specific, and safer to produce than viral culture and that are significantly less expensive to manufacture. Antigens so produced can be used for production of antibodies or antisera for competition assays, as reagents for mapping epitopes, as affinity-chromatography ligands for purification of antibodies or protein, and as research reagents. Their initial use in some hepatitis B assays may be primarily a cost-reduction application, but in other applications (e.g., HIV diagnostic tests) they present the first opportunity to commercially produce an otherwise very expensive antigen. Recombinant-DNA-produced antigens are also being used to develop safer vaccines, but not, however, without some consideration of the structural nature of immunodominant epitopes and the adequacy of the immune response.

Conservation in the 5' flanking sequences of transcribed members of the Caenorhabditis elegans major sperm protein gene family.

The major sperm proteins (MSPs) are encoded in the Caenorhabditis genome by a multigene family with more than 50 genes dispersed in small clusters at three chromosomal loci. In spite of their dispersed locations, all of the MSP genes appear to be expressed at the same time exclusively in the testis, indicating co-ordinate temporal and spatial regulation of these dispersed genes. Many of the MSP genes must be transcribed, because RNA hybridization with gene-specific probes showed that individual genes each contribute less than 3% to the total poly(A)+ RNA, and 13 out of 14 sequenced cDNAs came from different genes. Primer extension assays from MSP mRNA showed that most of the MSP mRNAs must be initiated at position -35 from the translation start codon. Extensive similarity was found in the first 100 nucleotides of genomic sequence flanking the start codons of ten MSP genes from different chromosomal locations. All MSP genes contained a consensus ribosome binding site, a consensus TATA homology 27 nucleotides distal to the site of mRNA initiation, and ten highly conserved nucleotides adjacent to the site of initiation. All the MSP genes contained the sequence AGATCT located approximately 65 nucleotides upstream from the transcriptional start, but little or no similarity was found more distal to this. Some of these conserved sequences may be cis-acting control elements that ensure the cell and temporal specificity of transcription of these co-ordinately regulated genes.

Genomic organization of major sperm protein genes and pseudogenes in the nematode Caenorhabditis elegans.

The major sperm proteins (MSPs) are a family of closely related, small, basic proteins comprising 15% of the protein in Caenorhabditis elegans sperm. They are encoded by a multigene family of more than 50 genes, including many pseudogenes. MSP gene transcription occurs only in late primary spermatocytes. In order to study the genomic organization of transcribed MSP genes, probes specific for the 3' untranslated regions of sequenced cDNA clones were used to isolate transcribed genes from genomic libraries. These and other clones of MSP genes were located in overlapping cosmid clones by DNA fingerprinting. These cosmids were aligned with the genetic map by overlap with known genes or in-situ hybridization to chromosomes. Of 40 MSP genes identified, 37, including all those known to be transcribed, are organized into six clusters composed of 3 to 13 genes each. Within each cluster, MSP genes are not in tandem but are separated by at least several thousand bases of DNA. Pseudogenes are interspersed among functional genes. Genes with similar 3' untranslated sequences are in the same cluster. The six MSP clusters are confined to only three chromosomal loci; one on the left arm of chromosome II and two near the middle of chromosome IV. Additional sperm-specific genes are located in one cluster of MSP genes on chromosome IV. The multiplicity of MSP genes appears to be a mechanism for enhancing MSP synthesis in spermatocytes, and the loose clustering of genes could be a result of the mechanism of gene duplication or could play a role in regulation.

The glyceraldehyde-3-phosphate dehydrogenase gene family in the nematode, Caenorhabditis elegans: isolation and characterization of one of the genes.

The isolation and genomic sequence of one of possibly four glyceraldehyde-3-phosphate dehydrogenase genes in the nematode, Caenorhabditis elegans is presented. The complete nucleotide sequence of the coding as well as the noncoding flanking regions of this gene has been determined. The deduced amino-acid sequence agrees with the sequence of typical glyceraldehyde-3-phosphate dehydrogenase enzymes and its molecular weight of 36,235 agrees with its size determined previously (Yarbrough, P. and Hecht, R. (1984) J. Biol. Chem. 259, 14711-14720). That this isolated gene encodes a nematode glyceraldehyde-3-phosphate dehydrogenase is additionally confirmed by demonstrating its immunoreactivity to an anti-nematode glyceraldehyde-3-phosphate dehydrogenase antibody after its expression as a fusion protein with dihydrofolate reductase. Codon utilization follows a pattern typical of other expressed nematode genes. The gene is split by two introns that are highly conserved in comparison to other introns observed in C. elegans. The placement of one of these introns is conserved with respect to the chicken glyceraldehyde-3-phosphate dehydrogenase gene. Within the 5' flanking sequence homology to actin and the homology 2 block of the major myosin gene (unc-54) is noted. It is of interest that the 3' flanking region contains a CAAAT box, followed by a TATAAT box, before an open reading frame of a closely linked gene that also contains a small AT-rich intron with the nematode consensus splice junction.

Expression of chimeric genes in Caenorhabditis elegans.

We have shown the expression of transformed genes in the nematode Caenorhabditis elegans using a new gene fusion system. Vectors consisting of the flanking regions of a collagen gene (col-1) or a major sperm protein gene of C. elegans fused to the Escherichia coli uidA gene, encoding beta-glucuronidase, were microinjected into worms and found to be propagated as high-copy extrachromosomal tandem arrays. We have detected beta-glucuronidase activity in transformed lines, and have shown that the activity is dependent upon the correct reading frame of the construction and on the presence of the worm sequences. The enzyme activity was shown to be encoded by the chimeric beta-glucuronidase gene by co-segregation analysis and by inactivation with specific antisera. Expression is at a very low level, and seems to be constitutive. We have used histochemical techniques to visualize the enzyme activity in embryos.

Use of bacterial DHFR-II fusion proteins to elicit specific antibodies.

Plasmids containing the coding region of the type II dihydrofolate reductase (DHFR) specified by R388 have been used to alter the amino acid (aa) sequence at the C-terminus of this protein. These plasmids have a unique cloning site in the C-terminal portion of the 78-aa coding region. Insertions of DNA fragments into this site produced plasmids that code for proteins with 6- to 80-aa extensions. The vectors were constructed to terminate translation in all three phases beyond the position of insertion of foreign DNA. Random DNA fragments from the major sperm protein (MSP) gene of Caenorhabditis elegans produced by DNase I cleavage were inserted into these vectors. Cell extracts from colonies containing MSP sequences were examined by gel electrophoresis and immunoblotting. One of the hybrid DHFR-MSP proteins was isolated and antibody was prepared to it. This antibody preparation reacted with MSP in immunoblots of purified MSP and whole cell extracts of the worm. A rapid purification procedure for the DHFR is presented.

The effects of selected rice and soybean pesticides on the eggs of Psorophora columbiae.

Twenty-five pesticides used in the production of rice and soybeans in Texas were tested in the laboratory to determine their toxicity to the eggs of Psorophora columbiae. A reduction in hatching rate occurred when eggs were treated with a herbicide formulation containing thiobencarb and with one containing a tank mixture of propanil and molinate. A carbaryl formulation induced hatching of eggs prior to their exposure to the hatching stimulus. Reduced survival to second instar of larvae hatching from treated eggs was observed with insecticide formulations of acephate, carbofuran, malathion, methyl parathion and toxaphene; a fungicide formulation of triphenyltin hydroxide and the tank mixture of the herbicides, propanil and molinate.

Requirement for protein synthesis in the regulation of a circadian rhythm by serotonin.

Serotonin (5-HT, 5-hydroxytryptamine) regulates the phase of a circadian pacemaker located within the eye of Aplysia. We are attempting to define the cellular and biochemical events involved in the regulatory pathway through which serotonin acts. Previously, we have shown that an activation of adenylate cyclase and an increase in cAMP are events in the 5-HT phase-shifting pathway. In this paper, we examine the role of protein synthesis in mediating the effect of 5-HT and cAMP on the phase of the circadian rhythm. Exposure of eyes to anisomycin, an inhibitor of protein synthesis, completely blocked the advance shift in phase produced by 5-HT. Although anisomycin by itself can produce phase shifts, it did not affect the rhythm at the phases where the blocking experiments were performed. The specificity of action of anisomycin was investigated in two ways. First, deacetylanisomycin, an analogue of anisomycin that is inactive in inhibiting protein synthesis, did not affect the shift in phase produced by 5-HT. Second, anisomycin did not inhibit two other effects of 5-HT on the eye that also appear to be mediated by cAMP: an inhibition of spontaneous optic nerve activity and an increase in the photosensitivity of the eye. The step in the 5-HT phase-shifting pathway that is sensitive to anisomycin appears to occur after the cAMP step because anisomycin also inhibits the ability of 8-benzylthio-cAMP to shift the phase of the rhythm. We have also examined whether 5-HT directly regulates the synthesis of any proteins in the eye. Using two-dimensional gel electrophoresis, we have found that 5-HT appears to increase the synthesis of a protein with an apparent molecular weight of 67,000. Our results indicate that protein synthesis is necessary for 5-HT to shift the phase of the rhythm and that 5-HT appears to regulate the expression of at least one protein in the eye.

Isolation and characterization of a sperm-specific gene family in the nematode Caenorhabditis elegans.

The major sperm protein (MSP) of the nematode Caenorhabditis elegans is a low-molecular-weight (15,000) basic protein implicated in the pseudopodial movement of mature spermatozoa. Its synthesis occurs in a specific region of the gonad and is regulated at the level of transcription (M. Klass and D. Hirsh, Dev. Biol. 84:299-312, 1981; S. Ward and M. Klass, Dev. Biol. 92:203-208, 1982; Klass et al., Dev. Biol. 93:152-164, 1982). A developmentally regulated gene family has been identified that codes for this MSP. Whole genomic blots, as well as analysis of genomic clone banks, indicate that there are between 15 and 25 copies of the MSP gene in the nematode genome. Southern blot analysis also indicates that there is no rearrangement or amplification within the MSP gene family during development. No evidence was found of methylation at various restriction sites surrounding the MSP gene family, and similarly, no correlation between methylation and expression was observed. Three distinct members of this MSP gene family have been cloned, and their nucleotide sequences have been determined. Differential screening of a cDNA clone bank made from polyadenylated mRNA from adult males yielded 45 male-specific clones, 32 of which were clones of MSP genes. One of these cDNA clones was found to contain the entire nucleotide sequence for the MSP, including part of the 5' leader and all of the 3' trailing sequence. Genomic clones bearing copies of the MSP genes have been isolated. At least one of the members of this gene family is a pseudogene. Another member of the MSP gene family that has been cloned from genomic DNA contains the entire uninterrupted structural sequence for the MSP in addition to a 5' flanking sequence containing a promoter-like region with the classic TATA box, a sequence resembling the CAAT box, and a putative ribosome-binding sequence. The 3' trailing sequences of the genomic and the cDNA clones contain an AATAAA polyadenylation site.

A method for the isolation of longevity mutants in the nematode Caenorhabditis elegans and initial results.

The free-living nematode Caenorhabditis elegans is used as a genetically manipulable experimental system for the study of aging. Utilizing a temperature-sensitive sterile strain with a normal life span, a method is described for the isolation of mutant strains with significantly increased life spans. Eight mutant strains were isolated each having increased life spans. Two mutant strains were spontaneous dauer formers, accounting for their increased longevity. Another was chemotaxis-defective, causing reduced food intake which could account for its increased life span. Five mutants suffered from varying degrees of paralysis affecting their rate of pharyngeal pumping and food ingestion. The high correlation of the decreased rate of food ingestion of these mutants with their increased longevity is interpreted as indicating that the increased longevity is most likely due to reduced caloric intake. These results appear to indicate that specific life span genes are extremely rare or, alternatively, life span is controlled in a polygenic fashion.