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Features of spondyloarthritis around the world.

This article elucidates the prevalence and pathogenic roles of the MHC and microbial infections and clinical features and treatment of SpA across different populations from the arctic and subarctic regions to Central America, Asia, and Africa. Preliminary evidence suggests significant genetic and environmental influences on the onset and presentation of SpA, particularly AS, in these populations, which are different than those reported in white Caucasians; however, community surveys and longitudinal and case control studies are difficult to undertake in many of the developing countries. Thus, most of the currently available data have been devised from short-term and retrospective studies and should be treated with caution. Differences in referral and follow-up practices and the availability of rheumatology expertise and relevant resources may explain some of the differences observed in the populations discussed in this article. Furthermore, widely accepted criteria for the classification of SpA may not be applicable to non-Caucasians and need to be evaluated in these subjects. With gradual improvement in the economic status in many of the developing countries in Asia and Africa, it is hoped that with improvement in medical services, more physicians and specialty clinics in rheumatology, and changing referral patterns, better documentation of the various aspects of different SpA can be achieved. Future research should focus on the evaluation of specific risk or protective factors in population groups to better delineate the relative importance of genetic and environmental effects in the pathogenesis of SpA.

Arthritis, Psoriatic↗

Problems in the management of type III (severe) open fractures: a new classification of type III open fractures.

Between 1976-1979, 87 Type III open fractures (in 75 patients) were treated at the Hennepin County Medical Center. Factors leading to increased morbidity in Type III fractures were: massive soft-tissue damage; compromised vascularity; severe wound contamination; and marked fracture instability. This study demonstrates, because of varied severity and prognosis, that the current designation of Type III open fracture is too inclusive. We recommend, therefore, that Type III open fractures be divided, in order of worsening prognosis, into three subtypes. Type IIIA--Adequate soft-tissue coverage of a fractured bone despite extensive soft-tissue laceration or flaps, or high-energy trauma irrespective of the size of the wound. Type IIIB--Extensive soft-tissue injury loss with periosteal stripping and bone exposure. This is usually associated with massive contamination. Type IIIC--Open fracture associated with arterial injury requiring repair. Wound sepsis in the three subtypes were: Type IIIA, 4%, IIIB, 52%; and IIIC, 42%; while amputation rates were, respectively, 0%, 16%, and 42%. Only two patients developed osteomyelitis, and 12 patients had delayed or nonunions. Five patients died, all as a result of multisystem trauma. The bacterial pathogens in infected open fractures have changed dramatically over the years. In the present series (1976-1979), 77% of infections were due to Gram-negative bacteria, compared with 24% previously (1961-1975). A change of antibiotic therapy from a first-generation cephalosporin alone to a combination of a cephalosporin and an aminoglycoside, or a third-generation cephalosporin, is currently indicated in Type III open fractures.

Adolescent↗

Genetic methods for the detection of microbial pathogens. Identification of enterotoxigenic Escherichia coli by DNA colony hybridization: collaborative study.

Enteropathogenic Escherichia coli strains may produce a cholera-like, heat-labile enterotoxin (LT) as a virulence factor. The gene that codes for LT can be purified by recombinant DNA techniques and used as a genetic probe for DNA hybridization. These probes detect enterotoxigenic strains as well as strains that may not manifest toxin production but carry the genetic information to do so. In this study, 13 laboratories tested 3 known and 25 unknown (10 positive and 15 negative) cultures of E. coli for the presence of the LT gene. The isolates had been tested and classified by the mouse Y-1 adrenal cell test and an enzyme-linked immunosorbent assay. Cultures were spotted on nitrocellulose filters on MacConkey agar and incubated. Colonies were lysed in situ and their DNA was hybridized to 32P-labeled, purified LT gene DNA (provided to the collaborators). Positive colonies were identified by autoradiography. Of 325 samples, 315 (96.9%) were identified correctly and 10 were misclassified; there were 6 false negative and 4 false positive identifications. Chi-square values indicated that the method agreed with the previous classification and was equally efficient in distinguishing positive and negative samples (95.7 and 98.1%, respectively). The method has been adopted official first action.

Autoradiography↗

Phenotypic and genotypic characterization of Vibrio vulnificus: proposal for the substitution of the subspecific taxon biotype for serovar.

The classification of Vibrio vulnificus strains into two biotypes has been maintained on the basis of phenotypic properties and eel virulence. Biotype 2 is virulent for eels, negative for the indole reaction, and serologically homogeneous (serogroup E), whereas strains of biotype 1 are avirulent, indole positive, and serologically heterogeneous. In the present study, we phenotypically and genotypically characterized 21 V. vulnificus isolates, recovered mainly from northern Europe, by comparing them with reference strains of both biotypes to look for new isolates of biotype 2. The results of this work revealed that the majority of isolates virulent for eels presented phenotypic traits previously considered characteristics of biotype 2 and specific ribotypes with HindIII. However, among the new isolates we found (i) a serogroup E strain virulent for eels but indole positive and (ii) one isolate not belonging to serogroup E but pathogenic for eels. Since no biochemical test for specific serogroup can with certainty be associated with eel virulence, we propose to classify V. vulnificus strains into serovars instead of biotypes. Thus, we suggest serovar E as the denomination of those strains previously classified as biotype 2. Finally, the occurrence of serogroup E in eels cultured in Norway and Sweden, as well as from human infections and shrimp, has been demonstrated.

Bacterial Typing Techniques↗

Comparison of chitinase isozymes from yam tuber--enzymatic factor controlling the lytic activity of chitinases.

To evaluate the anti-pathogen activity of chitinases, we developed a new method for measuring the lytic activity, and investigated the correlation of the lytic activity with the enzymatic properties by using four chitinase isozymes, Chitinases E, F, H1 and G, which had been purified from yam tubers by column chromatography. Chitinases E, F and H1 had high lytic activity against the plant pathogen, Fusarium oxysporum, but Chitinase G did not. Chitinase E, which is the family 19 chitinase, was similar to Chitinases F and G in its antigenecity, but not to Chitinase H1 or H2. Chitinases H1 and H2 were recognized by the anti-Bombyx mori chitinase antibody, suggesting that Chitinases H1 and H2 are family 18 chitinases like B. mori chitinases. Chitinases E, F and H1 had two optimum pH ranges of 3-4 and 7.5-9 toward glycolchitin, but Chitinase G had only one optimum pH value of 5. Chitinases E, F and H1 had higher affinity to the polymer substrate, glycolchitin, than Chitinase G. These results suggest that the lytic activity of plant chitinases may be related to the chitin affinity and probably to the characteristic optimum pH value, or two values, but not related to its classification. The correlation of the lytic activity of a chitinase isozyme with its elicitor specificity is also discussed.

Animals↗

[Autonomic symptoms in diabetic polyneuropathies].

200 years have gone by since the autonomic disturbance in diabetes mellitus has been described for the first time ever. There is a great deal of information on the close relationship between somatic and visceral symptoms in diabetic polyneuropathy (PNP), so that there should be talked about only of one form of manifestations within the meaning of a distal symmetric somatovisceral PNP. The longer fibres such as the vagal fibres of the viscus, sympathetic fibres of the eye are affected at first and more intensively in the autonomic region same as in the sensory and motor region. Due to the fact that for reasons of fragmentary knowledge pathogenetically substantiated classification of the autonomic disturbances in diabetic PNP is not at hand, such a classification is being made from organotopic and phenomenologic aspects. Frequently, afferent denervation of an organ results in enhancing the effects of an autonomic innervation dysfunction, as for instance in unnoticed hypoglycaemia, in order to modify the symptoms, as for instance in rectal incontinence with unnoticed defecation, or rather to let new symptoms appear, for instance loss of testicular pain. In recent years, appropriate methods of examinations were tested for the clinical routine, permitting to give evidence of autonomic dysfunctions before clinical manifestation. It is still unclear to what extent such subclinical abnormalities are reversible with a more favourable regulation of the metabolic process, for instance with the aid of continuous subcutaneous insulin injections. An impressive symptom of innervation dysfunctions of the cardiovascular system is orthostatic hypertension that may, in exceptional cases, even lead to confinement to bed. The most important pathogenic factor seems to be vascular denervation. A pronounced tachycardia at rest, frequently found in diabetics, is the result of the failure of the vagal autonomic system, and, after additional destruction of the sympathetic fibres, it adjusts itself to a lower level that cannot be changed by reflex mechanisms. Cardialgia absent in the case of myocardial ischemia is a factor of an increased mortality of long-term diabetics. The correlation between vascular denervation and arteriosclerosis or mediasclerosis, respectively, is being under discussion. Denervation on the gastrointestinal tract has an effect on the motility and excretory functions. The innvervation dysfunctions lead to sialadenosis by changing the composition of saliva. In most cases esophageal dysfunction is not perceived by the patient.(ABSTRACT TRUNCATED AT 400 WORDS)

Autonomic Nervous System Diseases↗

Gene expression diversity among Mycobacterium tuberculosis clinical isolates.

Intraspecies genetic diversity has been demonstrated to be important in the pathogenesis and epidemiology of several pathogens, such as HIV, influenza, Helicobacter and Salmonella. It is also important to consider strain-to-strain variation when identifying drug targets and vaccine antigens and developing tools for molecular diagnostics. Here, the authors present a description of the variability in gene expression patterns among ten clinical isolates of Mycobacterium tuberculosis, plus the laboratory strains H37Rv and H37Ra, growing in liquid culture. They identified 527 genes (15 % of those tested) that are variably expressed among the isolates studied. The remaining genes were divided into three categories based on their expression levels: unexpressed (38 %), low to undetectable expression (31 %) and consistently expressed (16 %). The expression categories were compared with functional categories and three biologically interesting gene lists: genes that are deleted among clinical isolates, T-cell antigens and essential genes. There were significant associations between expression variability and the classification of genes as T-cell antigens, involved in lipid metabolism, PE/PPE, insertion sequences and phages, and deleted among clinical isolates. This survey of mRNA expression among clinical isolates of M. tuberculosis demonstrates that genes with important functions can vary in their expression levels between strains grown under identical conditions.

Bacterial Proteins↗

[Severity of glomerular damage with IgA nephropathy and renal prognosis: a comparison between pattern classification and calculated classification].

In our laboratory, a semi-quantitative pattern classification (PC) for the distribution pattern of glomerular sclerotic lesions in biopsied renal specimens with IgA nephropathy has been utilized, and found to be quite beneficial for predicting the patient's prognosis. In the present study conducted to re-evaluate this classification, 503 patients with IgA nephropathy (male/female, 256/247; mean age: 32.1 +/- 13.5 yrs; follow-up: 9.3 +/- 4.5 yrs) were used. The patients had been divided originally into 5 groups based on a previous PC: minimal, mild, moderate, severe and advanced groups. Their glomerular lesions were classified as mild, moderate, severe and global sclerosis, and were given scores of 1-4 points. The mean glomerular score was then calculated for each patient, as a value of the calculated classification (CC), and all patients were then re-divided into 5 groups based on their scores. The renal survival curves in the CC were similar to those in PC, and no significant differences in the renal survival rates were found between the classifications in each group, thus suggesting that the CC has a similar predictive power for renal survival. Although 7 of 39 cases (18%) with global sclerosis in PC groups 4 and 5 shifted down to CC group 3, of 61 patients with global sclerosis in PC group 1 who had a good prognosis, 26 cases (43%) shifted up to the CC group 2 and 6 cases (8%) changed to the CC group 3. As a result, the predictive power in patients in the lower CC groups was lost for the renal survival rate. In conclusion, statistical comparison between the PC and CC groups revealed that global sclerosis presents in non/minimally affected glomeruli as a nonspecific alteration. Severely advanced cases also possess a high incidence of globally sclerotic glomeruli (87%), and therefore the occurrence of global sclerosis may involve two different pathogenic mechanisms.

Adolescent↗

The distance between bacterial species in sequence space.

Despite the revolution caused by information from macromolecular sequences, the basis of bacterial classification remains the genus and the species. How do these terms relate to the variety of bacteria that exist on earth? In this paper, the inter- and intraspecies differences in amino acid sequence of several bacterial electron transport proteins, cytochromes c, and blue copper proteins are compared. For the soil and water organisms studied, bacterial species can be classed as "tight" when there is little intraspecies variation, or "loose" when this variation is large. For this set of proteins and organisms, interspecies variation is much larger than that within a species. Examples of "tight" species are Pseudomonas aeruginosa and Rhodobacter sphaeroides, while Pseudomonas stutzeri and Rhodopseudomonas palustris are loose species. The results are discussed in the context of the origin and age of bacterial species, and the distribution of genomes in "sequence space." The situation is probably different for commensal or pathogenic bacteria, whose population structure and evolution are linked to the properties of another organism.

Amino Acid Sequence↗

Clonorchis sinensis: pathogenesis and clinical features of infection.

When larvae of C. sinensis reach the biliary system and mature, the flukes provoke pathological changes, both as a result of local trauma and of toxic irritation. The appearances vary with duration and severity of the infestation, but they are sufficiently distinctive and characteristic to allow a classification into four phases as follows; 1st phase, desquamation of epithelial cells, 2nd phase, hyperplasia and desquamation of epithelial cells, 3rd phase, hyperplasia and desquamation of epithelial cells, and adenomatous tissue formation, and 4th phase, marked proliferation of the periductal connective tissue with scattered abortive acini of epithelial cells and fibrosis of the wall of the bile duct. The onset of symptoms and signs is at times gradual, at times sudden. Chill and fever up to 40 degrees C occur during the acute stage, i.e. the period less than a month after parasite invasion. And a few weeks later, the chronic stage follows with the classical clinical features. In general, symptoms and signs can be classified as follows: mild, essentially symptomless, progressive, with irregular appetite, gastrointestinal disturbances, oedema, hepatomegaly, etc., and severe, with a syndrome associated with portal cirrhosis and hypertension. Pathogenic changes and complications are generally restricted to foci, but may eventually affect the whole liver. Calculi, acute suppurative cholangitis, recurrent pyogenic cholangitis, cholecystitis, hepatitis, and acute pancreatitis are important complications. Carcinoma of the liver is often found in association with clonorchiasis, too.

Clonorchiasis↗

The polymicrobial origin of intestinal infections in homosexual men.

To determine the microbial cause and the clinical and pathologic correlates of anorectal and intestinal symptoms in homosexually active men, we performed comprehensive microbiologic studies, anoscopy, sigmoid-oscopy, and rectal biopsy in men examined in a clinic for sexually transmitted diseases. Enteric pathogens were found in 95 of 119 consecutive homosexual men with anorectal or intestinal symptoms and in 29 of 75 randomly selected homosexual men without such symptoms (P less than 0.001). The syndromes of proctitis, proctocolitis, and enteritis were differentiated on the basis of predominant symptoms and findings on anoscopy and sigmoidoscopy. Neisseria gonorrhoeae, herpes simplex virus, Chlamydia trachomatis (non-lymphogranuloma venereum serotypes), and Treponema pallidum were associated with 80 per cent of cases with symptomatic proctitis. Known causes of colitis, including Campylobacter jejuni, Campylobacter fetus fetus, Shigella flexneri, Chl. trachomatis (lymphogranuloma venereum serotypes), Entamoeba histolytica, and Clostridium difficile, were identified in 60 per cent of the cases of proctocolitis. Giardia lamblia was the only agent significantly correlated with enteritis. These data demonstrate that intestinal symptoms in homosexual men are attributable to a complex spectrum of microorganisms, but that careful clinical classification can serve as a guide to the selection of microbiologic studies and to a rational initial choice of therapy.

Adult↗

Evidence for diverse types of large plasmids in tumor-inducing strains of Agrobacterium.

Homology between the large plasmids of 15 pathogenic Agrobacterium strains isolated from various parts of the world has been measured and was found to vary over a wide range, from 3 to 100%. Two genetically distinct groups of plasmids can be identified: one closely related to the plasmid of A. tumefaciens A6, an octopine-utilizing strain, and the other closely related to the plasmid of A. tumefaciens C-58, a nopaline-utilizing strain. The plasmids of four Agrobacterium strains do not belong to either group. One of these four strains utilizes octopine, one utilizes nopaline, and two utilize neither. Three strains contained two large plasmids. In one of these strains, the two plasmids were not homologous to one another. Chromosomal homologies for the Agrobacterium strains surveyed also vary over a wide range, but do not correlate with plasmid homologies. Neither do plasmid homologies correlate with any numerical classification scheme. The significance of these plasmid homology studies for crown gall tumorigenesis is considered.

Chromosomes, Bacterial↗

Systemic immunoregulatory and pathogenic functions of homeostatic chemokine receptors.

The adoptive immune response relies on a precise temporal and spatial positioning of lymphocytes within lymphoid and nonlymphoid tissues. Chemokines, constitutively expressed or induced during inflammation provide a flexible navigation system directing lymphocytes into specific microcompartments. Precision and specificity in this process are achieved by varying patterns of chemokine receptors expressed on the cell surface of lymphocytes in the course of cell differentiation. The chemokine receptors CXCR5 and CCR7 are principal regulators for targeting T cells, B cells, and dendritic cells into secondary lymphoid organs. The analyses of knockout mice have been instrumental in exploring the crucial role of these receptors for the compartmentalization of secondary lymphoid organs into functionally separated T and B cell zones. Aside from the homeostatic recirculation of lymphocytes and inflammatory processes, chemokine receptors are also involved in malignancies such as lymphoproliferative diseases and cancer metastasis. Recent results from our laboratory present evidence for the involvement of CCR7 in the dissemination of neoplastic cells in classic Hodgkin disease. There is also accumulating evidence for the involvement of CXCR5 in the formation of ectopic follicles as observed in lymphomas or autoimmune diseases. In addition, CCR7 and CXCR5 have been identified as useful markers in the classification of functionally distinct subsets of T-helper cells, which will lead to a better understanding of T cell memory and T cell effector function in lymphoid system homeostasis and disease.

Animals↗

Specific immunoabsorption.

Rapidly progressive glomerulonephritis occurs in patients developing autoantibodies to the glomerular basement membrane (GBM) and in multisystem vasculitic syndromes such as Wegener's granulomatosis (WG) and microscopic polyarteritis (MPA). In anti-GBM disease the pathogenicity of the autoantibodies has been established by transfer experiments; new solid-phase radioimmunoassays (RIAs) for circulating autoantibodies allow early diagnosis and effective monitoring of treatment. Sequential measurements of antibody levels showed that their generation is self-limiting (even without treatment) and that their production can be arrested more quickly with immunosuppressive therapy (cyclophosphamide and high dose steroids) together with intensive plasma exchange. In systemic vasculitis, no pathogenic agent has been identified and the diseases are rarely self-remitting. In WG, antibodies to cytoplasmic components of normal human neutrophils (and monocytes) were reported to be detectable by indirect immunofluorescence, with titres correlating with disease activity. We confirmed this and showed that antigen can be extracted from normal human neutrophils and used as ligand in a solid-phase RIA. Sera from patients with other forms of systemic vasculitis, such as MPA, as well as WG, are positive in this assay. The antigens have been further characterized by HPLC fractionation on a Toyosoda TSK gel filtration column. In WG, antibodies were directed towards cytoplasmic fractions of 100, 6 and 2 kDa; in MPA, antibody reacted only with the 100 kDa fraction. These findings suggest a humoral pathogenesis in these disorders and indicate that this approach may be helpful in the classification, diagnosis and monitoring of therapy in the systemic vasculitides. Further characterization of the autoantigen and its potential use in specific immunoabsorption are discussed.

Alkaline Phosphatase↗

Immunological inter-strain crossreactivity correlated to 18S rDNA sequence types in Acanthamoeba spp.

Various species of the genus Acanthamoeba have been described as potential pathogens; however, differentiation of acanthamoebae remains problematic. The genus has been divided into 12 18S rDNA sequence types, most keratitis causing strains exhibiting sequence type T4. We recently isolated a keratitis causing Acanthamoeba strain showing sequence type T6, but being morphologically identical to a T4 strain. The aim of our study was to find out, whether the 18S rDNA sequence based identification correlates to immunological differentiation. The protein and antigen profiles of the T6 isolate and three reference Acanthamoeba strains were investigated using two sera from Acanthamoeba keratitis patients and one serum from an asymptomatic individual. It was shown, that the T6 strain produces a distinctly different immunological pattern, while patterns within T4 were identical. Affinity purified antibodies were used to further explore immunological cross-reactivity between sequence types. Altogether, the results of our study support the Acanthamoeba 18S rDNA sequence type classification in the investigated strains.

Acanthamoeba↗

The tau R406W mutation causes progressive presenile dementia with bitemporal atrophy.

Frontotemporal dementia (FTD) and Alzheimer's disease (AD) are two frequent causes of dementia that share both clinical and neuropathological features. Common to both disorders are the neurofibrillary tangles consisting of aggregations of hyperphosphorylated tau protein. Recently, a number of different pathogenic mutations in the tau gene have been identified in families with FTD and parkinsonism linked to chromosome 17 (FTDP-17). In the present study, a Swedish family with presenile degenerative dementia with bitemporal atrophy was screened for mutations in the tau gene. As a result, the R406W mutation in exon 13 was identified in all affected cases. This mutation has previously been reported in two different FTDP-17 families of Dutch and Midwestern American origin. Common features to these two kindreds and our family are the late age at onset and long duration of the disease. Our pedigree as well as the American one show early memory impairment and pronounced temporal lobar atrophy similar to AD, while the Dutch cases show more FTD features. This further illustrates the large clinical variability among cases with tau mutations and stresses the importance of genetic classification in addition to the traditional clinical classification of neurodegenerative disorders.

Age of Onset↗

Early involvement of the nervous system by human immune deficiency virus (HIV). A study of 79 patients.

We report on 79 patients of different stages of human immune deficiency virus (HIV) infection according to the Walter-Reed staging classification (WR). Comparing the HIV antibody content per weight IgG in serum and cerebrospinal fluid (CSF), 54 patients (68%) showed higher antibody activity in CSF than in serum, indicating intrathecal antibody production and thus a local challenge with the virus. The percentage of patients with these antibodies in CSF increased from stage WR 1 (33%) to WR 5 (90%). It decreased again in WR 6 (68%). Twenty-one patients with intrathecally produced antibodies but without evidence for opportunistic or preexistent neuropsychiatric diseases were further analyzed. Even in stages WR 1 and 2 these patients showed distinct clinical signs. These consisted mostly in apathic personality change (n = 13), peripheral neuropathy (n = 8) or mild hemisyndrome (n = 9). Progression to severe dementia solely caused by HIV encephalitis seems to be possible. More often acceleration of the mental disorder indicates a synergistic action of other pathogens. Our study gives further evidence for very frequent, early and clinically active involvement of the nervous system by the HIV infection.

Acquired Immunodeficiency Syndrome↗

[Retraction pockets, pathological entity?].

Retraction pockets are not a pathological entity per se but take after various ear diseases, with which they share the same morphological eardrum alterations. The authors believe that any holistic evaluation of retraction pockets, as though these were forming a single group of like pathogenic origin, i.e., tubal dysfunction, would be artificial and raise therapeutic problems. The statistical analysis of the causes for retraction pocket formation provides little information. Otologists are still looking into chronic otitis media and cholesteatoma as a possible, long-suspected, unproved etiology. Electron microscopy and, more particularly, istological-enzymological analyses of mounts prepared by the authors have shown, in some cases, the anomalous presence, in the pocket, of Langerhans' cells, which the authors consider as strongly indicative of cholesteatoma. While confirming the clinical diagnosis, anatomopathological examination allows to differentiate poor-prognosis retraction pockets from benign ones. The pathogenesis of these pockets is still poorly understood. It is the authors' contention that tympanic invagination is more likely traceable to some biopathological/biochemical phenomenon than to occupational mechanical disorders involving the tube. The clinical characteristics of retraction pockets are the basis for their classification into three groups, according to their evolutional tendency. Thus, developing cholesteatomas bear a poor prognosis; sequelae of benign otitis are associated with small risk; lastly, there is a small group of pockets the evolution of which is hard to specify. The authors believe that such differentiation between retraction pockets is mandatory to have a clear picture of therapeutic indications, and to assess the various outcomes.

Cholesteatoma↗