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[Obtaining antisera to Pseudomonas aeruginosa and Proteus antigens for performing immunoenzyme analyses in clinical practice].

The data presented in this work indicate that specific antisera to P. aeruginosa and Proteus antigens can be produced by using extracts from these microorganisms, destroyed by ultrasonic treatment or by multiple freezing and thawing, for the immunization of rabbits. Blood serum samples from patients with purulent septic complications were studied for the presence of P. aeruginosa and Proteus antigens in ELISA with the use of peroxidase-labeled antibodies from antisera to P. aeruginosa and Proteus. This investigation revealed that during the first 3 days from the beginning of the clinical manifestations of the complications P. aeruginosa and Proteus antigens were detected in 86.4% and 83.4% of the patients, respectively. In the subsequent bacteriological study of wound discharge from these patients the corresponding microflora was detected.

Animals↗

[Vaccine from soluble antigens for the specific therapy of Proteus infection].

A vaccine prepared from Proteus soluble antigens obtained by the disintegration of microbial cells with hydroxylamine is proposed. In animal experiments the vaccine has proved to be nontoxic when injected in large single doses or in smaller doses over a prolonged period and capable of protecting mice and rabbits from Proteus infection. No pronounced postvaccinal complications have been registered in humans immunized with the vaccine. The possibility of using the vaccine for immunizing donors with the aim of obtaining hyperimmune anti-Proteus plasma and for the active vaccinal therapy of patients with Proteus infection has been shown.

Animals↗

Origin and spread of Pseudomonas aeruginosa, Proteus and Klebsiella during twenty years in an infectious hospital.

Bacteriological examinations carried out in an infectious hospital revealed that the occurrence of Pseudomonas and Proteus grew 4-fold, and the rate of Klebsiella positive cultures 3.5-fold between 1958 and 1977. On the other hand, the occurrence of Staphylococcus aureus decreased to the half since 1961. The occurrence of Gram-negative facultative pathogens started to increase in the surgical wards in the fifties and the rise lasted until the mid-sixties. Pseudomonas aeruginosa was the most frequent among them. In contrast, Escherichia coli dominated and P. aeruginosa was the least frequent in the non-surgical wards. Here the Gram-negative facultative pathogens showed a more rapid increase and the incidence of P. aeruginosa and Proteus kept rising throughout the whole examination period. When Gram-negative facultative pathogens of hospital origin were colonizing, the proportion of sick persons versus symptomless carriers was significantly higher than in the case of extrahospital colonization on the basis of the records of 300 P. aeruginosa, 300 Proteus and 300 Klebsiella positive patients. This proportion changed parallel with the rate of the strains of hospital origin. The number of patients who acquired P. aeruginosa, Proteus or Klebsiella extrahospitally, kept continuously rising between 1958 and 1971. Thus, the advance of Gram-negative facultative pathogens is due not ony to nosocomial causes.

Carrier State↗

Cutaneous manifestations of proteus syndrome: correlations with general clinical severity.

BACKGROUND: Proteus syndrome is a rare congenital disorder with progressive asymetric overgrowth of multiple tissues. OBJECTIVES: To determine the range of cutaneous findings in Proteus syndrome and to correlate cutaneous findings with overall disease severity. DESIGN: A prospective cohort study was performed at the National Institutes of Health, a tertiary referral center. PATIENTS: Twenty-four consecutive children and adults with Proteus syndrome meeting recent diagnostic criteria. INTERVENTIONS: Physical examination, including complete skin examination, and review of medical records. MAIN OUTCOME MEASURES: Frequency of skin findings; correlation of skin findings with extracutaneous findings; cluster analysis of findings. RESULTS: The 24 patients had skin abnormalities: 22 (92%) had lipomas, 21 (88%) had vascular malformations, 20 (83%) had cerebriform connective tissue nevi on the soles of the feet, 16 (67%) had epidermal nevi, 9 (38%) had partial lipohypoplasia, and 5 (21%) had patchy dermal hypoplasia. Some patients had localized alterations in skin pigmentation and hair or nail growth. Patients with a greater number of skin abnormalities tended to have a greater number of extracutaneous abnormalities. The number of abnormalities tended to increase with age up to 8 years. CONCLUSIONS: Patients with Proteus syndrome exhibit a variable but defined assortment of cutaneous findings. The correlation between numbers of cutaneous and extracutaneous is consistent with the postulated mosaic basis for this syndrome.

Adolescent↗

Clinical differentiation between Proteus syndrome and hemihyperplasia: description of a distinct form of hemihyperplasia.

Proteus syndrome is a rare and highly variable hamartomatous syndrome that can affect multiple organ systems. It is characterized by hyperplastic lesions of connective tissue, vascular malformations, linear verrucous epidermal nevi, and hyperostoses. The cause of the disorder is unknown, but the current working hypothesis is that it is caused by a mosaic alteration that leads to a highly variable phenotype, equal sex ratio, sporadic occurrence, and discordant monozygotic twins. Herein we describe our experience with 18 patients with a referring diagnosis of Proteus syndrome. It was found that imaging studies are very useful for the characterization of the syndrome. One finding was that splenic hyperplasia can be a manifestation of Proteus syndrome. Analysis of the clinical data shows that Proteus syndrome is frequently confused with "hemihyperplasia." A distinct subtype of hemihyperplasia is defined that includes static or mildly progressive hemihyperplasia and multiple lipomata.

Adolescent↗

Elattoproteus syndrome: delineation of an inverse form of Proteus syndrome.

A 7-year-old boy had partial lipohypoplasia and patchy dermal hypoplasia involving large areas of his body. These areas of deficient growth were similar to those described in many cases of Proteus syndrome. Paradoxically, however, he had only few and rather mild lesions of disproportionate overgrowth. This unusual case is taken as a clue to postulate the Elattoproteus syndrome, an inverse form of Proteus syndrome. The paradoxical coexistence of hyperplastic and hypoplastic lesions may reflect a twin spot phenomenon. The patient would carry at the Proteus locus one allele giving rise to overgrowth of tissues (Pleioproteus allele--from Greek pleion, meaning plus), whereas the other allele would cause deficient growth of tissues (Elattoproteus allele--from Greek elatton, meaning minus). At an early stage of embryogenesis, somatic recombination would give rise to two different populations of cells homozygous for either allele. From a heuristic point of view, one may postulate the existence of the Elattoproteus syndrome, a purely inverse form of Proteus syndrome that would develop in the absence of the Pleioproteus allele.

Alleles↗

Growth hormone (GH), insulin-like growth factors (IGFs), and IGF-binding protein-3 (IGFBP-3) in a child with Proteus syndrome.

Proteus syndrome is a congenital hamartomatous disorder characterized by partial overgrowth involving all germ layers. A somatic mutation model has been proposed since familial cases are extremely rare. We report on a 3-year-old girl with typical manifestations of Proteus syndrome, including local, asymmetric hypertrophy of various parts of the body. Total body length was reduced. Serum levels of IGF-I and especially IGF-II and their major growth hormone dependent binding protein (IGFBP-3) were significantly reduced, although growth hormone secretion after a pharmacological stimulus was normal. In vitro studies of fibroblasts derived from hypertrophied tissue showed normal IGF-I production and somewhat reduced IGF-II and IGFBP-3 production as compared to normal human skin fibroblasts. Affinity cross-linking experiments showed that fibroblasts of the affect tissue in Proteus syndrome produced an unusual pattern of IGF bindings proteins containing large amounts of an IGFBP with high affinity to IGF-II. The data suggest that IGF production is generally disturbed in Proteus syndrome with imbalanced levels of specific IGFBP in affected tissue.

Adult↗

Reassessment of the Proteus syndrome literature: application of diagnostic criteria to published cases.

The medical care of patients affected by rare disorders depends heavily on experiences garnered from prior cases, including those patients evaluated by the treating physician and those published in the medical literature. The utility of published cases is wholly dependent upon accurate diagnosis of those patients. In our experience, the rate of misdiagnosis in Proteus syndrome (PS) is high. Diagnostic criteria have been published, but these criteria have not been applied consistently and were published after many case reports appeared in the literature. We reviewed 205 cases of individuals reported to have PS in the literature and three of us independently applied the diagnostic criteria to these case reports. Our initial diagnostic congruence was 97.1% (199/205); the discrepancies in six cases were easily resolved. Only 97 (47.3%) of reported cases met the diagnostic criteria for PS; 80 cases (39%) clearly did not meet the criteria; and although 28 cases (13.7%) had features suggestive of PS, there were insufficient clinical data to make a diagnosis. Reported cases that met the PS criteria had a higher incidence of premature death, and other complications (scoliosis, megaspondyly, central nervous system abnormalities, tumors, otolaryngologic complications, pulmonary cystic malformations, dental and ophthalmogic complications) compared to those in the non-Proteus group. The cases that met the criteria were more often male, which has implications for hypotheses regarding the etiology and pathophysiology of PS. We also studied the attributes that led authors to conclude the reported patients had PS when we concluded they did not. We found that two of the diagnostic criteria (disproportionate overgrowth and connective tissue nevi) were often misinterpreted. In PS, the abnormal growth is asymmetric, distorting, relentless, and occurred at a faster rate compared to the rest of the body. Furthermore, PS was associated with irregular and disorganized bone, including hyperostoses, hyperproliferation of osteoid with variable calcification, calcified connective tissue, and elongation of long bones with abnormal thinning. In contrast, non-Proteus cases displayed overgrowth that was asymmetric but grew at a rate similar to the growth found in unaffected areas of the body. Also, the overgrowth in non-Proteus cases was associated with normal or enlarged bones together with ballooning of the overlying soft tissues. Taken together, these data show that (1) PS diagnostic criteria sort individuals with asymmetric overgrowth into distinct groups; (2) individuals with PS were more likely to have serious complications; (3) PS affects more males than females; and 4) the published diagnostic criteria are useful for clinical care and research. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299/suppmat/index.html.

Diagnosis, Differential↗

Chromosomally encoded cephalosporin-hydrolyzing beta-lactamase of Proteus vulgaris RO104 belongs to Ambler's class A.

Proteus vulgaris RO104 strain produces a chromosomally encoded beta-lactamase that confers resistance to various beta-lactam antibiotics including methoxyimino third-generation cephalosporins. The beta-lactamase hydrolyzes first- and second-generation cephalosporins efficiently and cefotaxime to a lesser extent. Catalytic activity is inhibited by low concentrations of clavulanic acid and sulbactam. By its broad-spectrum substrate profile, beta-lactamase of Proteus vulgaris RO104 belongs to the group 2e defined by Bush. The protein purified to homogeneity by a four-step procedure was characterized by a pI of 8.31 and a specific activity of 1200 U/mg. The beta-lactamase was digested by trypsin, endoproteinase Asp-N and chymotrypsin. Amino-acid sequence determinations of the resulting peptides allowed the alignment of the 271 amino-acid residues of the protein which did not contain any cysteine residue. From amino-acid sequence comparisons, Proteus vulgaris RO104 beta-lactamase was found to share about 68% identity with the chromosomally mediated beta-lactamases of Klebsiella oxytoca D488 and E23004. Therefore, the cephalosporin-hydrolyzing beta-lactamase of Proteus vulgaris RO104 belongs to Ambler's class A.

Amino Acid Sequence↗

Structure of a new neutral O-specific polysaccharide of Proteus penneri 34.

The O-specific polysaccharide of Proteus penneri strain 34 was studied using 1H and 13C NMR spectroscopy, including 2D COSY, TOCSY, NOESY, and H-detected 1H, 13C HMQC experiments. The following structure was established, which is unique among the known structures of Proteus O-antigens:-->4)-beta-D-Glcp-(1-->3)-beta-D-GalpNAc-(1-->4)-beta- D-GalpNAc-(1-->4)-beta-D-Galp-(1-->. Accordingly, no cross-reaction was observed between P. penneri 34 O-antiserum and O-antigens of other Proteus strains. Therefore, the strain studied should belong to a new Proteus serogroup O65.

Animals↗

Proteus rettgeri infections: a review.

Proteus rettgeri is an aerobic gram-negative bacillus that displays marked resistance against most of the antibiotics presently available. This organism causes infections usually confined to the urinary tract of certain types of compromised patients. Occasionally, it is recovered from soft tissue abscesses, and rarely from the blood and respiratory tract. Proteus rettgeri is notorious for causing nosocomial outbreaks of urinary tract infections in urological and physical medicine wards. Our experience with a patient who had bacteremia with a multi-drug resistant strain of Proteus rettgeri prompted a review of the literature concerning infections with this organism. The salient features of these reports are discussed and summarized. Data on the antibiotic sensitivity of 15 other strains of Proteus rettgeri are included.

Adolescent↗

Studies of introital colonization in women with recurrent urinary infections. V. The inhibitory activity of normal vaginal fluid on Proteus mirabilis and Pseudomonas aeruginosa.

Normal vaginal fluid from premenopausal volunteers was inoculated with 10 strains of Proteus mirabilis and 14 strains of Pseudomonas aeruginosa at pH's of 4.3, 4.6 and 4.9. All bacteria were killed at pH 4.3. Nine of 10 strains of Proteus mirabilis and 12 of 14 Pseudomonas aeruginosa were killed at pH 4.6. Only 4 of 14 strains of Pseudomonas aeruginosa were killed at pH 4.9, while 8 of 10 strains of Proteus mirabilis were killed at the same pH. We conclude that in comparison to the common 0 group strains of Escherichia coli, vaginal fluid is more bactericidal to Proteus mirabilis and Pseudomonas aeruginosa and that these observations may help explain the relative infrequency of bacteriuria owing to the organisms.

Escherichia coli↗

Germline and germline mosaic PTEN mutations associated with a Proteus-like syndrome of hemihypertrophy, lower limb asymmetry, arteriovenous malformations and lipomatosis.

Germline PTEN mutations cause Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRR), two hamartoma-tumour syndromes, and somatic PTEN alterations have been shown to participate, to a greater or lesser extent, in a wide variety of sporadic neoplasia. PTEN is a tumour suppressor and dual-specificity phosphatase which affects apoptosis via its lipid phosphatase activity in the phosphoinositol-3-kinase and AKT pathway as well as inhibiting cell spreading via the focal adhesion kinase pathway. CS and BRR share some features, such as hamartomas and lipomatosis. To determine whether other syndromes characterized by overgrowth and lipomas are part of the PTEN syndrome spectrum, we ascertained six individuals with overgrowth and lipomas but who did not meet the diagnostic criteria for CS or BRR. Five had Proteus syndrome and one, a Proteus-like syndrome. When germline DNA and DNA from at least one involved tissue per case were examined for PTEN mutations, only the Proteus-like patient was found to harbour a germline R335X mutation. Interestingly, a lipomatous mass, an epidermoid naevus and arteriovenous malformation tissue, all of which were sampled from physically distinct sites, were all found to carry a second hit R130X mutation on the allele opposite the germline R335X. Both mutations have been described in CS and BRR. We postulate that the second hit, R130X, occurred early in embryonic development and may even represent germline mosaicism. Thus, PTEN may be involved in Proteus-like syndrome with its implications for cancer development in the future.

Arteriovenous Malformations↗

Asymmetric reduction of racemic sulfoxides by dimethyl sulfoxide reductases from Rhodobacter capsulatus, Escherichia coli and Proteus species.

The enantioselective reduction of racemic sulfoxides by dimethyl sulfoxide reductases from Rhodobacter capsulatus, Escherichia coli, Proteus mirabilis and Proteus vulgaris was investigated. Purified dimethyl sulfoxide reductase from Rhodobacter capsulatus catalysed the selective removal of (S)-methyl p-tolyl sulfoxide from a racemic mixture of methyl p-tolyl sulfoxide and resulted in an 88% recovery of enantiomerically pure (R)-methyl p-tolyl sulfoxide. Rhodobacter capsulatus was shown to be able to grow photoheterotrophically in the presence of certain chiral sulfoxides under conditions where a sulfoxide is needed as an electron sink. Whole cells of Rhodobacter capsulatus were shown to catalyse the enantioselective reduction of methyl p-tolyl sulfoxide, ethyl 2-pyridyl sulfoxide, methylthiomethyl methyl sulfoxide and methoxymethyl phenyl sulfoxide. Similarly, whole cells of Escherichia coli, Proteus mirabilis and Proteus vulgaris reduced these sulfoxides but with opposite enantioselectivity.

Anaerobiosis↗

Proteus syndrome: report of the first Japanese case with special reference to differentiation from Klippel-Trenaunay-Weber syndrome.

This is the first report of a Japanese girl with Proteus syndrome. She presented with growth acceleration and precocious development of the left breast as well as macrodactyly, hemihypertrophy, a subcutaneous preaxillary mass, portwine stains, connective tissue nevi, and a depigmented macule. All these abnormalities were confined to the left side of her body. Although most of the manifestations fit those of Proteus syndrome, the presence of the portwine stains and hemihypertrophy also suggested Klippel-Trenaunay-Weber syndrome. The findings in our patient suggest that the most important characteristic distinguishing Proteus syndrome from Klippel-Trenaunay-Weber syndrome is the presence of functional abnormalities such as a growth spurt and precocious breast development. Proteus syndrome may be genetically different from the Klippel-Trenaunay-Weber syndrome.

Child, Preschool↗

Epigenetic regulation of carnitine metabolising enzymes in Proteus sp. under aerobic conditions.

Proteus sp. is able to catalyse the reversible transformation of crotonobetaine into L(-)-carnitine during aerobic growth. Contrary to other Enterobacteriaceae no reduction of crotonobetaine into gamma-butyrobetaine could be detected in the culture supernatants. Activities of L(-)-carnitine dehydratase, carnitine racemasing system and crotonobetaine reductase could be determined enzymatically in cell-free extracts of Proteus sp. Small amounts of gamma-butyrobetaine were found in cell-free extracts, indicating that it accumulates in the cell and inhibits the crotonobetaine reductase. Crotonobetaine and L(-)-carnitine were able to induce enzymes of carnitine metabolism. gamma-Butyrobetaine and glucose repress carnitine metabolism in Proteus sp. Other betaines are neither inducers nor repressors. Monoclonal antibodies against purified CaiA from Escherichia coli O44K74 recognise an analogous protein in cell-free extract of Proteus sp. No cross-reactivity could be detected with monoclonal antibodies against purified CaiB and CaiD from E. coli O44K74.

Acyltransferases↗

Effect of salicylate on expression of flagella by Escherichia coli and Proteus, Providencia, and Pseudomonas spp.

Osmotic stress, salicylate, and Mar (multiple antibiotic resistance) mutation are known to block the expression of the OmpF porin. Since these conditions have also been shown to inhibit the expression of P and CFA fimbriae in Escherichia coli, we speculated that they might affect the expression of flagella as well. Hyperosmotic conditions have been shown to block the synthesis of flagellin and expression of flagella in E. coli (C. Li, C. J. Louise, W. Shi, and J. Adler, J. Bacteriol. 175:2229-2235, 1993). In the current study, sodium salicylate was found to inhibit the motility of E. coli, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, and Providencia stuartii in a reversible, concentration-dependent manner. Swarming did not occur at 20 mM sodium salicylate. Salicylate also blocked the synthesis of flagellin in E. coli. Phenotypic Mar mutants of E. coli derived from motile strains were amotile. Flagella were markedly reduced as determined by scanning electron microscopy when P. mirabilis was grown in broth containing 20 mM salicylate. Salicylate had no apparent effect, however, on expression of a 40-kDa porin protein in P. mirabilis. This finding suggests that the noted effect of salicylate on Proteus spp. may be mediated through a mechanism other than porin production or that the Proteus porin may not be analogous to OmpF in E. coli. Salicylate decreased the motility of Pseudomonas cepacia but had no effect on Pseudomonas aeruginosa. The exact mechanism by which salicylate exerts its effect is not known, but it appears to be related to osmoregulation.

Bacterial Outer Membrane Proteins↗

Fragmentation of 23S rRNA in strains of Proteus and Providencia results from intervening sequences in the rrn (rRNA) genes.

Intervening sequences (IVSs) were originally identified in the rrl genes for 23S rRNA (rrl genes, for large ribosomal subunit, part of rrn operon encoding rRNA) of Salmonella enterica serovars Typhimurium LT2 and Arizonae. These sequences are transcribed but later removed during RNase III processing of the rRNA, resulting in fragmentation of the 23S species; IVSs are uncommon, but have been reported in at least 10 bacterial genera. Through PCR amplification of IVS-containing regions of the rrl genes we showed that most Proteus and Providencia strains contain IVSs similar to those of serovar Typhimurium in distribution and location in rrl genes. By extraction and Northern blotting of rRNA, we also found that these IVSs result in rRNA fragmentation. We report the first finding of two very different sizes of IVS (113 bp and 183 to 187 bp) in different rrl genes in the same strain, in helix 25 of Proteus and Providencia spp.; IVSs from helix 45 are 113 to 123 bp in size. Analysis of IVS sequence and postulated secondary structure reveals striking similarities of Proteus and Providencia IVSs to those of serovar Typhimurium, with the stems of the smaller IVSs from helix 25 being similar to those of Salmonella helix 25 IVSs and with both the stem and the central loop domain of helix 45 IVSs being similar. Thus, IVSs of related sequences are widely distributed throughout the Enterobacteriaceae, in Salmonella, Yersinia, Proteus, and Providencia spp., but we did not find them in Escherichia coli, Citrobacter, Enterobacter, Klebsiella, or Morganella spp.; the sporadic distribution of IVSs of related sequence indicates that lateral genetic transfer has occurred.

Base Sequence↗