Biomedical subjects

A Schmitz

Publications and source records attributed to A Schmitz.

At least 55 records · Page 3Linked to original sources

PubMed2000

Chromosomal abnormalities in hypoprolific boars.

Four new chromosomal rearrangements are reported in the domestic pig: 3 reciprocal translocations, rcp(4;12)(p13;q13) in a crossbred boar, rcp(1;7)(q17;q26) in a Large White purebred boar, rcp(1;6)(q17;q35) in a purebred synthetic paternal line boar, and a pericentric inversion inv(2)(p13q11) in a crossbred boar. The 1/7 reciprocal translocation and the pericentric inversion were detected in animals that had sired small litters. The effect of the 1/7 translocation was accurately determined: -4.5 piglets born per litter, i.e. -36%. Both the 1/6 and 1/7 reciprocal translocations were of maternal origin. All the chromosomal rearrangements were highlighted using GTG and/or RBG banding techniques. Chromosome painting experiments were also carried out to confirm the proposed hypotheses for the three reciprocal translocations.

Animals↗

PubMed2000

Morphometric partitioning of respiratory surfaces in amphioxus (Branchiostoma lanceolatum Pallas).

The anatomical diffusing factors (ADFs), defined as the ratio of surface area to the thickness of the diffusion barrier, of possible respiratory surfaces of adult amphioxus (Branchiostoma lanceolatum) were evaluated using stereological methods. The ADF is greatest for the lining of the atrium and for the skin covering the segmental muscles. Calculation of the diffusing capacities for O(2) revealed that the lining of the atrium makes up nearly 83 % of the entire diffusing capacity (8.86 x 10(-3) microl min(-1)mg(-1)kPa(-1) while the skin over the segmental muscles (9%), the skin over the metapleural fold (4%) and the gill bars (4%) are of minor importance. The diffusing capacity of surfaces lying over coelomic cavities makes up 76% of the whole diffusing capacity, which is consistent with the hypothesis that the coelom may function as a circulatory system for respiratory gases. Muscles have approximately 23% of the entire diffusing capacity, indicating that they may be self-sufficient for O(2) uptake. The diffusing capacity of the blood vessels in the gill bars is only 1% of the total. Thus, the 'gills' lack significant function as respiratory organs in amphioxus (lancelets).

Animals↗

PubMed2000

The thioredoxin boxes of thyroglobulin: possible implications for intermolecular disulfide bond formation in the follicle lumen.

Multimerization of thyroglobulin (TG) takes place extracellularly in the thyroid follicle lumen and is regarded as a mechanism to store TG at high concentrations. Human thyroglobulin (hTG) has been shown to multimerize mainly by intermolecular disulfide cross-links. We recently noted that TG of various mammalian species contains three highly conserved thioredoxin boxes (CXXC). This sequence is known to underlie the enzymatic activity of protein disulfide isomerase (PDI). As hTG formed intermolecular disulfide bonds in the absence of other proteins depending on the redox conditions and hTG concentration, the CXXC-boxes of TG might provide the structural basis for self-assisted intermolecular cross-linking. To test this hypothesis we prepared a recombinant TG fragment containing the three thioredoxin boxes. This fragment exhibited a redox activity amounting to about 10% of the activity of PDI at redox conditions supposed to be present in the extracellular space. This activity might be supplemented by the oxidizing system of the apical cell surfaces of thyrocytes facing the follicle lumen. Indeed, incubation of hTG with peroxidase and H202 resulted in intermolecular disulfide bridge formation. Our results suggest a combined mechanism of self-assisted and peroxidase-mediated disulfide bond formation leading to the intermolecular cross-linking of lumenal hTG.

Animals↗

PubMed2000

[++Scintimammography: a new imaging technique for diagnosis and follow-up of breast cancer].

99m Tc MiBi has emerged as a new imaging technique for primary breast carcinomas. The aim of this study was to analyze the diagnostic performance and the additional information provided by scintimammography (SMN). Two hundred and forty consecutive women referred to surgery for abnormalities breast or suspicious breast cancer were scanned before surgery. Sensitivity and specificity were respectively 92% and 53%. PPV: 77.5% and PVN: 79.3%. All false negative scans occurred in cancers 1 cm. SMN detected multiple foci of uptake in the same breast in 13%, that were all confirmed to be multifocal disease and histology. Controlateral focal uptake was also detected; at this time 5/27 are confirmed to be bilateral breast neoplasms; 22 patients are in follow-up. SMN is reliable in the diagnosis of breast cancer and also with difficult cases of mammography. Moreover, SMN provides additional qualitative information in 19.6% of breast carcinomas, such as chest wall infiltration, multifocal or bilateral breast cancer.

Adenocarcinoma, Mucinous↗

PubMed1999

Fine deletion mapping of chromosome 8p in non-small-cell lung carcinoma.

Several somatic genetic alterations have been described in non-small-cell lung carcinomas (NSCLC). Recurrent chromosomal deletions have suggested the presence of tumor-suppressor genes specifically involved in lung carcinogenesis. For one of these, 2 non-overlapping regions have been proposed on the short arm of chromosome 8, encompassing the LPL and NEFL genes. The LPL region has been extensively studied in NSCLC and other cancer types. Two genes, N33 and PRLTS, have been identified, but the small number of mutations excludes their involvement in the vast majority of tumors. In order to delineate a reliable region of deletional overlap on chromosome 8p in NSCLC, a series of 77 NSCLC was studied for 34 microsatellite polymorphisms distributed on chromosome 8p, using multiplex-PCR amplification. After purification of tumor nuclei by flow cytometry based on either the abnormal DNA index or the presence of a high expression of cytokeratin, allelic losses on chromosome 8p were observed in 39% of cases. Measurement of DNA index showed that 62% of tumors were hyperploid; allelic losses were more frequent in hyperploid than in diploid tumors (54% vs. 14%; p < 10(-4)). Deletions of part of the short arm were observed in 7 instances. Our data allow definition of an interval of common deletion, flanked by the loci D8S511 and D8S1992, where the putative tumor-suppressor gene might be localized.

Carcinoma, Non-Small-Cell Lung↗

PubMed1999

Activation of membrane-associated procaspase-3 is regulated by Bcl-2.

The mechanism by which membrane-bound Bcl-2 inhibits the activation of cytoplasmic procaspases is unknown. Here we characterize an intracellular, membrane-associated form of procaspase-3 whose activation is controlled by Bcl-2. Heavy membranes isolated from control cells contained a spontaneously activatable caspase-3 zymogen. In contrast, in Bcl-2 overexpressing cells, although the caspase-3 zymogen was still associated with heavy membranes, its spontaneous activation was blocked. However, Bcl-2 expression had little effect on the levels of cytoplasmic caspase activity in unstimulated cells. Furthermore, the membrane-associated caspase-3 differed from cytosolic caspase-3 in its responsiveness to activation by exogenous cytochrome c. Our results demonstrate that intracellular membranes can generate active caspase-3 by a Bcl-2-inhibitable mechanism, and that control of caspase activation in membranes is distinct from that observed in the cytoplasm. These data suggest that Bcl-2 may control cytoplasmic events in part by blocking the activation of membrane-associated procaspases.

Apoptosis↗

PubMed1999

Aqueous ethyl cellulose dispersions containing plasticizers of different water solubility and hydroxypropyl methylcellulose as coating material for diffusion pellets. I. Drug release rates from coated pellets.

The present work investigates release mechanisms of theophylline pellets coated with an aqueous ethyl cellulose (EC) dispersion containing plasticizers and hydroxypropyl methylcellulose (HPMC) as a water soluble pore former. Three different drug release mechanisms from coated pellets can be determined as a function of the water solubility of the plasticizers and the ionic strength of the release medium. Coated pellets with the addition of more hydrophilic plasticizers such as triethyl citrate (TEC) or diethyl phthalate (DEP) show an approximate zero-order-release rate. In contrast, two-phase release profiles can be observed from pellets coated with dispersions containing hardly soluble plasticizers such as dibutyl phthalate (DBP) or dibutyl sebacate (DBS). Only in a release medium of high ionic strength the water soluble pore former will remain in the coating. Thus the drug diffuses through a hydrated swollen membrane containing EC, HPMC and insoluble plasticizer. The release mechanisms depend on the glass transition temperature of the ethyl cellulose and therefore on the migration of the plasticizers and the pore former. This was shown by investigation of the migration of the additives and the influence of the temperature of the release medium on the release. Additionally, the study investigates the effect of curing and storage conditions of coated pellets on the drug release rate.

Cellulose↗

PubMed1999

Deletion mapping of the tumor suppressor locus involved in colorectal cancer on chromosome band 8p21.

Several somatic genetic alterations have been described in colorectal carcinoma (CRC). Recurrent chromosomal deletions have suggested the presence of tumor suppressor genes (TSG) specifically involved in colorectal carcinogenesis. For one of them, two non-overlapping regions have been proposed on the short arm of chromosome 8, encompassing the LPL and NEFL genes. The short arm of chromosome 8 has been extensively studied in colorectal cancer and in other cancer types. Both regions have been reported as candidate loci for a TSG. In order to delineate a reliable region of deletional overlap on chromosome arm 8p in CRC, a series of 365 CRC samples was selected for the absence of microsatellite instability (RER, replication error); tumor and normal matched DNAs were studied for 54 microsatellite polymorphisms distributed on 8p using multiplex-PCR amplification. After purification of tumor nuclei by flow cytometry based on either the abnormal DNA index or the presence of a high expression of cytokeratin, complete allelic losses on 8p were observed in 48% of cases. Measurement of the DNA index showed that 88% of RER tumors were hyperploid. Complete allelic losses of only part of the short arm were observed on 26 occasions. These data allowed us to define a 1 cM interval of common deletion, flanked by the loci D8S1771 and NEFL, where a putative TSG may be localized.

Animals↗

PubMed1999

Transcapillary escape rate and albuminuria in Type II diabetes. Effects of short-term treatment with low-molecular weight heparin.

The relation between urinary albumin excretion rate (UAE), transcapillary escape rate of albumin (TERalb), haemostatic factors, ambulatory blood pressure, and metabolic variables was investigated in 45 Type II (non-insulin-dependent) diabetic patients without overt nephropathy or uncontrolled blood pressure. We enrolled 44 patients in a placebo controlled study to test the effects of 3 week long treatment with low-molecular weight heparin (tinzaparin) on the same variables. BMI, 24 h systolic and diastolic blood pressure, plasma concentrations of triglycerides, fasting glucose, factor VIII, von Willebrand factor (vWf), fibrinogen, alpha-2 macroglobulin, and fibronectin were notably higher in patients with increased albuminuria compared with normoalbuminuric patients, whereas the TERalb was similar in the two groups. TERalb correlated with fasting plasma glucose. UAE correlated more closely than TERalb with 24 h ambulatory blood pressure, vWf, and factor VIII. Urinary albumin excretion rate was unchanged during tinzaparin [28.9+/-5.6 vs 28.1+/-6.0 microg/min (geometric mean (antilog SD)] vs placebo (18.0+/-5.4 vs 17.6+/-5.3 microg/min), and no change was found in TERalb [6.3+/-1.6 vs 6.0+/-1.5%/h (means +/- SD), and 6.3+/-1.5 vs 5.6+/-1.8%/h; tinzaparin versus placebo, respectively]. Only minor changes were observed in blood pressure, lipids, glycaemic control and haemostatic factors. This study shows no correlation between albuminuria and transcapillary escape rate in Type II diabetic patients without overt nephropathy or uncontrolled-blood pressure. UAE is related to markers of atherosclerosis, endothelial injury and dysfunction, and haemostatic factors. Moreover, UAE correlates much more than TERalb with 24 h ambulatory blood pressure, von Willebrand factor, and factor VIII. Finally, short-term treatment with tinzaparin does not change the transvascular or glomerular leakage of albumin. These results indicate that TERalb is not a sensitive marker of microvascular dysfunction in such patients and that factors other than abnormal glycosaminoglycan metabolism may contribute to the vascular damage of these patients.

Adult↗

PubMed1999

Comparative karyotype of rat and mouse using bidirectional chromosome painting.

A comparative karyotype of rat (Rattus norvegicus) and mouse (Mus musculus) based on chromosome G-banding morphology, heterologous chromosome painting results and available gene mapping data is proposed. Whole chromosome painting probes from both species were generated by PARM-PCR amplification of flow sorted chromosomes. Bidirectional chromosome painting identifies 36 segments of syntenic homology and allows us to propose a nearly complete comparative karyotype of mouse and rat (except for RNO 13 p and RNO 19 p12-13). Seven segments completely covered the RNO chromosomes 3, 5, 8, 11, 12, 15 and 18. Eight segments completely covered the MMU chromosomes 3, 4, 6, 7, 9, 12, 18 and 19. The RNO chromosomes 5, 8, 18 show complete homology with the MMU chromosomes 4, 9 and 18, respectively. Bidirectional hybridization results clearly assign 16 segments to subchromosomal regions in both species. Interpretation of the results allows subchromosomal assignment of all the remaining segments apart from seven distributed on chromosomes MMU 15, MMU 10 B2-D3 and MMU 17 E3-E5. The proposed comparative karyotype shows overall agreement with available comparative mapping data. The proposed repartition of syntenic homologous segments between the two species provides useful data for gene-mapping studies. In addition, these results will enable the reconstruction of the karyotype of the Cricetidae and Muridae common ancestor and the definition of the precise rearrangements which have occurred in both mouse and rat lineages during evolution.

Animals↗

PubMed1999

Validity of rapid estimation of glomerular filtration rate in type 2 diabetic patients with normal renal function.

BACKGROUND: Rapid estimation of the renal function is widely used in clinical practice. METHODS: The validity of rapid estimation of renal function as well as long-term changes in renal function from the Cockcroft-Gault formula for estimation of creatinine clearance or from serum creatinine measurements was evaluated against the 51Cr-EDTA plasma clearance technique in 36 type 2 diabetic patients with normal renal function followed for 5.2 (2.7-7.5) (mean (range) years. RESULTS: Compared with 51Cr-EDTA plasma clearance the Cockcroft-Gault formula significantly underestimated glomerular filtration rate by 21%. The degree of underestimation was observed over the whole range of glomerular filtration rate studied and increased with increasing levels of isotopically measured glomerular filtration rates. Serum creatinine was not significantly associated with glomerular filtration rate. The average long-term change in renal function was significantly overestimated by the Cockcroft-Gault formula (-2.8+/-2.3 ml/min/year) compared with the measured rate (-1.5+/-2.5 ml/min/year) (P=0.002). The difference in change rate between the two methods was highest when the measured fall rates were small and tended to disappear in patients with faster fall rates. Changes in serum creatinine correlated significantly, but imprecisely, with the rate of decline of measured glomerular filtration rate (r=-0.48, P=0.003). The variability of the estimated fall rate of renal function was unacceptably high for all approaches. CONCLUSION: Valid estimates of glomerular filtration rate as well as the rate of change in glomerular filtration rate cannot be obtained by estimation of creatinine clearance from the Cockcroft-Gault formula or from serum creatinine concentration measurements in type 2 diabetic patients with normal renal function.

Aged↗

PubMed1999

Exercise and atherogenesis: where is the missing link?

Cardiovascular disease is the principal cause of death in Europe, the United States, and much of Asia. If sedentary people begin exercising on a regular basis, there is epidemiologal evidence of approximately 50% reduction in their risk of developing coronary heart disease. This article is an overview about epidemiology and pathogenesis of atherosclerotic lesions. It is intended to put forth the hypothesis that exercise modulates monocytes and T-lymphocytes and that this modulation is capable of guarding against atherosclerosis or inducing regression of atherosclerotic lesions. The literature does not provide sufficient data for drawing conclusions, but this article introduces a new direction of exercise immunological research. Prevention of atherosclerosis or regression of reversible forms of atherosclerotic lesions such as fatty streaks is the principal goal of preventive efforts. Sports medicine and exercise immunology may contribute significantly to the knowledge base if the cellular and molecular responses of regular exercise for atherogenesis are discovered.

Arteriosclerosis↗

PubMed1998

Repression of the mouse M-lysozyme gene involves both hindrance of enhancer factor binding to the methylated enhancer and histone deacetylation.

In many cases, gene repression mediated by CpG methylation has been demonstrated. Two different mechanisms have been postulated to explain the repressive effect of methylated CpG DNA: establishment of a repressive chromatin configuration and inhibition of DNA binding of transactivating factors. Using the M-lysozyme gene, we analyzed gene expression, CpG demethylation and the in vivo formation of enhancer/protein complexes after inducing demethylation or inhibiting histone deacetylases. We show that trans-cription of a methylated and silent mouse M-lysozyme gene can be induced upon the inhibition of histone deacetylases in the absence of demethylation or in vivo transactivating factor binding to the enhancer. In contrast, DNA demethylation induces both gene activity as well as enhancer complex formation. Therefore, both mechanisms play a role in lysozyme gene repression mediated by methylated DNA: (i) the enhancer cannot be loaded with transacting factors; and (ii) histone deacetylation inhibits transcription.

Acetylation↗

PubMed1998

Prokaryotic expression of porcine epidemic diarrhoea virus ORF3.

Wild type (wt) and cell culture adapted (ca) strains of the coronavirus PEDV differ in their ability to cause diarrhea in neonate piglets: the wt strains are virulent; the ca strains are attenuated. Comparison of the available nucleotide sequences obtained from the different viral isolates revealed almost complete sequence identity with the exception of variations and truncations in open reading frame 3 (ORF3) observed exclusively in ca-PEDV isolates. In order to study the biological function(s) of the putative ORF3 product, the molecule was expressed as a heterodimeric fusion protein in E. coli. ORF3 was fused in frame to the alkaline phosphatase gene. Simultaneously, the construct was designed to form specific heterodimers by inclusion of the well known leucine zipper motiv of Jun and Fos. The heterodimerization partner contained the E. coli heat-labile enterotoxin subunit B (LTB) to allow specific binding to the eukaryotic cell receptor GM1. Our results indicate that heterodimeric fusion protein containing a truncated form of ORF3 was produced in high amounts, carried the expected ORF3 epitope, showed phosphatase activity, and was able to bind to the GM1 receptor. In contrast, a fusion protein containing the entire sequence of the ORF3 product was produced in minute amounts, indicating that it may have biological activity in prokaryotes, which led to the reduction of the amounts of proteins expressed.

Animals↗

PubMed1998

[The effect of temperature and humidity on breath samples. Measurement of breath ethanol concentration in artificially respirated patients].

UNLABELLED: When looking for the possible cause of distortions in values measured for the determination of breath ethanol concentration (BEC) in artificially respirated patients, consideration must be given to the humidity and temperature of the gas examined. In the present study, the effects of humidified and warmed and of dry and cold air on the accuracy of a newly developed BEC measuring device, as compared to a reference model and to a conventional system, were examined in a lung model. METHODS: A temperature-regulated pediatric incubator was used containing a 10 I gas reservoir and a breath humidifier with temperature regulated water bath. This setup provided constant temperature and humidity in the gas examined during measurement period. In the 'expiration' the air was directed from the breath humidifier through a measuring unit via a 'mouthpiece' into the reference system (Alcotest 7110, Dräger Inc., Lübeck) and then out. The measuring unit consisted of sensors for the temperature and relative humidity, and of a connector for the three sample extraction systems (PES). PES I was the conventional system with a 100-cm gas-sample pipe (Alcomed 3010), PES II the newly developed system (AlcoMed 3011, both from Envitec, Wismar) with a 10-cm gas-sample pipe, and PES III with a 20-cm heated gas-sample pipe. During 'inspiration' 2 l of air was fed into the system to rinse the measuring unit and to fill the reservoir. 61 measurements were performed with dry and cold air, and 71 with humidified and warmed air, in the course of which the ethanol concentration was increased from 0 to 1.5/1000. Data were evaluated using regression analysis and the Bland & Altman method. RESULTS AND CONCLUSIONS: The constancy of the values set for temperature, relative humidity and absolute humidity in the lung model was given for all measurements. In the dry and cold air, the results from all three test systems coincided almost perfectly with the reference values. The measured BEC in the humidified and warmed air using sample-extraction systems II and III corresponded to a high degree with the reference, while in the case of PES I, only a moderate linear correlation was achieved. The temperature and humidity of the expired gas during artificial respiration influence the gas samples extracted for the purposes of BEC measurement. Newly developed sample-extraction systems II and III coincide with the reference system, even under respiration-simulated gas conditions.

Breath Tests↗

PubMed1998

[Clinical and nuclear magnetic resonance tomography diagnosis of glenoid labrum injuries].

PURPOSE: Clinical and radiological evaluation of labral tears remains challenging. It has been shown that intravenous administration of contrast agents produces an MR arthrographic effect without the need for intraarticular injection. This is the first study evaluating this new technique of indirect MR arthrography in diagnosis of glenoid labrum tears. METHODS: 28 patients with clinically suspected labral injuries were prospectively investigated (1.5 Tesla, flexible surface coil). A native MR exam of the shoulder (transverse and oblique-coronar orientation, T1-weighted spin-, proton density- and T2*-weighted gradient echo sequences) and indirect MR arthrography (transverse and oblique-coronar orientation, fat-suppressed T1-weighted spin-echo sequences, intravenous injection of gadopentetate dimeglumine [0.1 mmol/kg], followed by 10-15 min of joint movement) were performed. Results were confirmed by arthroscopy and/or open surgery. Additionally sensitivity evaluation of clinical tests for investigation of labral tears were performed. RESULTS: Indirect MR-Arthrography improved delineation of the glenoid labrum and hyaline cartilage significantly (p < 0.05). Sensitivity and specificity of indirect MR arthrography in diagnosis of labral injuries were 90% and 89% respectively, compared to 79% and 67% of the native MR exam. The reliability of the checked clinical tests is not sufficient enough to determine labral lesions (predictive value between 50 and 70%). CONCLUSION: Indirect MR-arthrography is a promising non-invasive technique in the evaluation of the glenoid labrum.

Adult↗

PubMed1998

Onchocerca ochengi: assessment of the Simulium vectors in north Cameroon.

In the savanna areas of tropical Africa, cattle are frequently infected with the filaria Onchocerca ochengi. This parasite is closely related to Onchocerca volvulus, the causative agent of human onchocerciasis (river blindness), and is capable of developing in the same vector, Simulium damnosum s.l. In North Cameroon, where both O. ochengi and O. volvulus are endemic, we carried out a field study (reported in this and 2 following papers) to examine to which extent the transmission of the 2 parasite species overlap and what influence this has on the epidemiology of human onchocerciasis. In this paper we report our experiments to determine which of the S. damnosum species in North Cameroon act as vectors of O. ochengi, how efficiently they do so and whether other Simulium species play a vector role. To this end, infected cattle were exposed near 5 rivers in different geographical areas. Among 14 Simulium species identified as aquatic and/or adult stages at these rivers, only 6 (S. squamosum, S. damnosum s.s., S. sirbanum, S. bovis, S. wellmanni and S. hargreavesi) were found to bite cattle in important numbers in at least 1 of the sites. The 3 species of the S. damnosum complex were all capable of ingesting microfilariae (mf) of O. ochengi and developing a proportion of them to infective larvae (L3). Whereas S. squamosum and S. damnosum s.s., the prevailing vectors in the Guinea and Sudan savanna respectively, showed a high vector competence (17% of ingested mf developed to L3), S. sirbanum, which was much rarer in both areas, appeared to have a much lower susceptibility (2%). Other boophilic Simulium species were only seen in certain sites and seasons, being either incapable of ingesting important numbers of O. ochengi mf from body regions where these mf were abundant (S. bovis, S. hargreavesi); not able to support the development of ingested mf to L3 (S. wellmanni), or bit cattle preferentially in the ears, where O. ochengi mf do not occur (S. hargreavesi). We conclude that in North Cameroon members of the S. damnosum complex are the only important vectors of O. ochengi, with S. squamosum and S. damnosum s.s. being the main vectors.

Animals↗

PubMed1998

Correlation between bending of the VM region and pathogenicity of different Potato Spindle Tuber Viroid strains.

Only 40 of the 359 nucleotides of Potato Spindle Tuber Viroid (PSTVd) represent the virulence-modulating (VM) region. Minor sequence variations in this domain distinguish mild from severe and even necrotic strains. Our recent hypothesis (Owens RA et al., 1996, Virology 222:144-158) that these differences result in varying degrees of bending of this part of the molecule could be tested experimentally. By in vitro transcription and partial double-strand formation, three types of model RNAs were prepared and subjected to electrophoresis in polyacrylamide gels: (1) Fragments representing the VM regions of six different PSTVd strains; (2) control fragments containing a bulge-loop as a rigid bend or an internal loop as a point of increased flexibility; and (3) dsRNAs of 36, 39, and 43 bp as length standards. Migration anomalies in gels of increasing percentage were evaluated and resulted in the following conclusions. In the absence of Mg2+, the VM regions differ only in terms of flexibility. Addition of Mg2+ induces conformational changes in these RNAs. All strains but Mild exhibit a rigid bend, and the angle of bending increases monotonically with the pathogenicity of the strain. The data are discussed in terms of a mechanism of pathogenicity, that protein-binding to the VM region is the primary pathogenic event.

Base Sequence↗