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Clinical and morphological correlations for transglutaminase 1 gene mutations in autosomal recessive congenital ichthyosis.

Autosomal recessive congenital ichthyosis (ARCI) is a group of inherited disorders of cornification in which progress has recently been made in the identification of pathogenic mechanisms causing the disease. Transglutaminase 1 (TGM1) has been found as a defective gene in a large fraction of patients with lamellar ichthyosis (LI), a severe inherited scaling disorder of the skin. We have previously performed molecular genetic studies of 38Finnish ARCI families and found six different mutations in 13 families of 38 (34%). In this study we compared the molecular genetic alterations with clinical and electron microscopic findings of these patients. Families were classified by electron microscopy in ichthyosis congenita (IC) types I, II, III, IV and a non-defined group. TGM 1 gene mutation was found in all of the IC type II and 1/3 of the IC type 1 families. Although electron microscopy is not always used to classify ARCI patients, it can distinguish groups which are parallel with molecular genetic findings. This finding might be useful in the classification of ARCI patients for further linkage studies. Clinically typical phenotype of the TGM1 mutation carrier includes large, thick, brownish scales, but ichthyosis of some of these patients tends to be milder.

Adolescent↗

Comparative phylogenetic analysis of cystatin gene families from arabidopsis, rice and barley.

The plant cystatins or phytocystatins comprise a family of specific inhibitors of cysteine proteinases. Such inhibitors are thought to be involved in the regulation of several endogenous processes and in defence against pests and pathogens. Extensive searches in the complete rice and Arabidopsis genomes and in barley EST collections have allowed us to predict the presence of twelve different cystatin genes in rice, seven in Arabidopsis, and at least seven in barley. Structural comparisons based on alignments of all the protein sequences using the CLUSTALW program and searches for conserved motifs using the MEME program have revealed broad conservation of the main motifs characteristic of the plant cystatins. Phylogenetic analyses based on their deduced amino acid sequences have allowed us to identify groups of orthologous cystatins, and to establish homologies and define examples of gene duplications mainly among the rice and barley cystatin genes. Moreover, the absence of a counterpart between the two monocots, as well as strong variations in the motifs that interact with the cysteine proteinases, may be related to a species-specific evolutionary process. This cystatin classification should facilitate the assignment of proteinase specificities and functions to other cystatins as new information is obtained.

Amino Acid Motifs↗

The low complexity proteins from enteric pathogenic bacteria: taxonomic parallels embedded in diversity.

The number and functions of the low complexity (LC) proteins from four enteric bacterial pathogens Escherichia coli O157, Vibrio cholerae, Helicobacter pylori and Campylobacter jejuni were compared. For this purpose the LC proteins were grouped into 3 categories for pairwise comparisons. These were COMMON, VARIANT and LC proteins with No Homologues (LCNH). Homologous LC proteins in both species in a given pairwise comparison were grouped as COMMON. LC Proteins of same function but not of low complexity in either of the species in a given pair were grouped as VARIANT. LC proteins without any homologues in either species were grouped as LCNH. Conservation patterns were inferred by comparing them under 3 functional classes CELLULAR PROCESSES (CP), TRANSPORT and MEMBRANE ASSOCIATED (TM) and CHARACTERISTIC (CH). In the COMMON category, highest similarity was found between E. coli O157 and V. cholerae on the one hand and H. pylori and C. jejuni on the other under the functional class CP. This parallels taxonomic classification in that E. coli and V. cholerae are classified under gamma subdivision of proteobacteria whereas H. pylori and C. jejuni are classified under the epsilon subdivision. The data from LCNH group, although more diffuse, was complementary the to pattern drawn from COMMON category in that the numbers of LCNH in the pair [E. coli O157, V. cholerae] and in [H. pylori, C. jejuni] were lowest. No consistent patterns were observed in the VARIANT category. These observations indicate that although low complexity segments are thought to undergo variations, species patterns do exist in a limited set of low complexity proteins that parallels taxonomic classification.

Amino Acid Sequence↗

Prolactin levels in the cerebrospinal fluid of patients with HIV infection and AIDS.

The objective of this study was to assess the levels of prolactin (PRL) in cerebrospinal fluid (CSF) of HIV-infected patients with regard to nonHIV-infected patients, and to assess the levels of prolactin in the CSF of HIV-infected patients with and without neurological HIV-involvement. Seventeen HIV-infected patients with different degrees of immunological and neurological involvement were studied. A second group of six HIV-seronegative patients with varying clinical conditions requiring lumbar punctures were included as controls. CSF was collected from patients and controls. Patients were studied neurologically and neuropsychologically, and computed tomography of the brain were performed. They were staged according to CDC clinical classification for HIV infection, and on the basis of tomographic findings into one of five stages. An additional classification for neurological involvement in AIDS was used. CD4+ cell counts, CSF studies, serum-prolactin levels and CSF-prolactin levels were performed as principal laboratory tests. CSF PRL concentrations were significantly higher in the HIV-infected group (n = 17) than the nonHIV infected control group (n = 6) (mean +/- s.d.; 5.77 +/- 2.22 vs. 3.53 +/- 0.69 x 10(-6) g l-1, respectively; p = 0.009, Mann-Whitney U-test). Moreover, even CSF-PRL concentration was higher in HIV-infected patients without cognitive impairment (stage 0 of the clinical classification), (n = 12) in comparison with nonHIV infected controls (n = 6) (mean +/- s.d.; 5.51 +/- 2.31 vs. 3.53 +/- 0.69 x 10(-1) g l-1, respectively; p = 0.028, Mann-Whitney U-test). There was a good correlation between serum and CSF-PRL levels in HIV-infected patients when measured by the Spearman Rank Test (rs = 0.773; p = 0.005). PRL raised serum levels were found in 4 out of 13 patients (30.73%). We conclude that higher levels of CSF-PRL are more frequently found in HIV-infected patients in comparison to uninfected controls. High levels of circulating PRL were also found in HIV-infected patients corroborating results from other work. A good correlation coefficient was found between circulating and CSF-PRL levels in HIV-infected patients, suggesting that disruption of the blood-brain barrier might account for a possible pathogenic mechanism.

AIDS Dementia Complex↗

RNU4ATAC-opathy: Clinical, molecular, and transcriptomic insights from a large cohort.

PURPOSE: We aim to better define the genotype and phenotype spectrum of RNU4ATAC-opathy, demonstrate the utility of RNA sequencing (RNA-seq) for variant classification, and highlight the challenges in detecting variants in this noncoding gene. METHODS: Sixty individuals with molecularly confirmed RNU4ATAC-opathy were recruited from multiple clinical and research centers internationally. RNA-seq was available for 7 affected individuals. RESULTS: We report the clinical and molecular findings of 60 individuals, including 42 not previously described, and 33 distinct RNU4ATAC variants, 13 of which are novel. Core features in this cohort-present in most individuals assessed and varying in severity-include microcephaly, short stature, skeletal anomalies, developmental delay, cerebral anomalies, skin conditions, and immune deficiency. Additional findings, such as diabetes, holoprosencephaly, and the absence of various core features in some individuals, highlight the broad phenotypic spectrum. All individuals who underwent RNA-seq showed a consistent pattern of minor intron retention. In 6 individuals, RNA-seq enabled the reclassification of variants of uncertain significance as likely pathogenic. Although RNU4ATAC variants are generally covered by clinical exomes, they are often overlooked in analysis because of their noncoding nature. CONCLUSION: This study highlights the variability of phenotypes and genotypes associated with RNU4ATAC-opathy. Laboratories should ensure RNU4ATAC and other noncoding genes are appropriately assessed by their analysis pipelines.

Lowry-Wood syndrome↗

Renal disease associated with HIV infection: a multicentric study of 60 patients from Paris hospitals.

Sixty HIV-infected patients presenting renal symptoms who underwent percutaneous renal biopsies were analysed. According to the CDC classification, 44 patients were staged in group IV, five in group III, and 11 in group II. Patients were divided in two groups according to their ethnic origin (29 black patients and 31 white patients). Risk factors such as homosexuality, multiple transfusions or intravenous drug abuse (IVDA) were identified in all white patients except two, but in only nine (31%) of the black patients. Three main patterns of renal disease were observed: focal and segmental glomerulosclerosis (FSGS) was found predominantly in black patients (23 black patients versus 3 Caucasians, P < 0.001) and was associated with the nephrotic syndrome; immune-complex-type glomerulonephritis (ICGN) was frequent in black and white patients (21% and 52% respectively) including four cases of IgA nephritis all seen in white patients; and 10 cases of lupus-like nephritis (4 black and 6 white patients). The frequent hypergammaglobulinaemia in those patients suggests a pathogenic role of polyclonal B cell activation in ICGN. Interstitial nephritis was present in 48 and 52% of the black and white patients respectively and did not seem related to drug toxicity or superimposed infectious disease. In addition to interstitial nephritis, the coexistence of multivisceral lymphocytic infiltration involving accessory salivary glands, liver and/or lung, found in six patients possibly suggests a virus-induced immune disorder.

AIDS-Associated Nephropathy↗

Cell preparation methods and criteria for sample adequacy. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: Cell Preparation Methods Standardized fixation and optimal staining Sampling of cervix, sampling error, homogenization of sample, subsampling Assessment of liquid-based preparations: efficacy and economic impact Training and transitional procedures before full implementation of new technologies Criteria for Sample Adequacy Clinician responsibility for collecting and providing representative sample to laboratory Collection instruments, number of slides Cellular content of samples: evidence of transformation zone (TZ) sampling, number of squamous cells present, obscuring factors Screening issues CONSENSUS POSITION The conventional cervical smear remains the standard method of cervical cancer screening but has limitations in individual test sensitivity and specificity. Sample takers should: (1) receive appropriate training in sample collection, (2) be held responsible for providing the laboratory with appropriate samples, and (3) have their performance monitored. The instruments used for sampling should collect cells from both the ectocervix and endocervix; optimally, TZ sampling, represented by the presence of endocervical or squamous metaplastic cells, should be identifiable in samples other than atrophic specimens. The adequacy of a specimen (as judged microscopically) does not guarantee that it is representative of the cervix. Each cytology report should include a comment on cellular content/adequacy of the specimen. Liquid-based preparations may overcome many of the inherent problems with the conventional cervical smear. ONGOING ISSUES: We need further data on the cost-effectiveness of making two slides from cervical specimens and/or using two samplers rather than a single one. Do we have enough information to make recommendations as to the appropriate type of sampler to be used in particular situations, such as routine screening? What is the best method of screening for/detecting endocervical glandular neoplasia? How are such terms as unsatisfactory and inadequate defined in cervical cytology classifications other than the Bethesda System? What number and types of epithelial cells should be present (visualized) in a cervical smear or liquid-based preparation for it to be considered adequate? Do we need to have evidence of TZ sampling in specimens taken during the follow-up period after treatment of squamous intraepithelial lesion or after detection of endocervical glandular neoplasia? What criteria for obscuring factors, such as blood and inflammation, should be used in assessing adequacy? Cost-benefit analyses of utilizing liquid-based preparations are needed. Should we inform women about the technical details of the test methods available or chosen by the laboratory? Are women in a position to decide which method is the most appropriate to assess their cervical scrape sample? We need to obtain more information about the properties of proprietary liquid fixative/transport media with respect to inactivation of viral pathogens, tuberculosis and other bacterial pathogens and suitability for immunobiologic and molecular tests, etc. We need to obtain more information on the use of stoichiometric stains and the limitations of Papanicolaou stain for image analysis systems. The use of liquid-based preparations for nongynecologic cytopathology and ancillary tests must be considered, including criteria for adequacy. We need to obtain more information on the time required for and best methods of training experienced cytotechnologists to become competent at assessing liquid-based cervical preparations.

Cell Biology↗

[Nucleotide sequence analysis of a species specific probe by an inserted fragment from recombinant plasmid pCX7 of L. interrogans sensu stricto serovar lai].

The etiological agents of leptospirosis are the pathogenic leptospires (L. interrogans sensu lato) which can be divided into 223 serovars organized into 23 serogroups. The serovar remains the basic taxon, but serotyping may now be accomplished and recognized by acceptable methods. Complementary molecular approaches are being used extensively to assess genetic relatedness amongst leptospires with restriction endonuclese analysis (REA), pulse field gel electrophoresis (PFGE) and DNA-DNA hybridization as well established tools. However, the method is cumbersome and unsuitable for routine application. To develop a sensitive and specific method for identification of pathogenic leptospires, a genomic library of L. interrogans sensu stricto serovar lai was constructed with the plasmid vector pUC9. A recombinant plasmid, designated pCX7 which has homologous fragment of pathogenic leptospires was screened from the bank. pCX7 could recognize pathogenic leptospiral DNA fragment 1.7 kb of strain 017 without cross hybridization to nonpathogenic leptospiral DNA. Inserted fragment of pCX7 DNA sequencing was performed by Dr. Yan Zhengxin (Max-Plank-Institut fur Biology, Tubingen, Germany). Insert fragment was cloned into pBluescript and sequenced by using ABI(Applied Bio. Systems, Model 373A). Nucleotide sequences were analyzed by Dr. Xiao Jianguo (Texas University Medical School and School of Public Health, Center for Infectious Diseases) using a suit of computer program (NIH). One open reading frame of 306 nucleotids were identified. There were identifiable initiation codons, terminators, pribnow box and sextama box within the sequenced regions. These results further confirmed that the little homology between L. interrogans sensu strito and L. borgpeterseni serovar javanica, L. inadai serovar ranarun and serovar manhao (L. genomospecies 2), L. biflexa serovar patoc, L. illini. pCX7 DNA probe could provide a base for identification and classification of leptospires.

DNA, Bacterial↗

Psychological subtypes of erectile dysfunction: results of statistically analyses and clinical practice.

In contrast to the impressive advances made in somatic research of erectile dysfunction (ED), psychogenic ED is mostly treated as a monolithic block or is merely defined by exclusion of organic factors. This paper proceeds from the assumption that a classification of psychological subtypes of ED is urgently needed and has to include a categorization of different pathogenetic mechanisms as well as a classification of interaction patterns with somatic risk factors. After a brief review of current approaches, psychological subtypes of ED are examined along two different lines of evidence. First, 236 consecutive patients from an ED outpatient. unit were included in a cluster analysis to identify homogeneous subgroups of cases. Three clusters emerged, whose main characteristics as well as most important discriminating variables were further explored by various statistical procedures. Second, on the basis of clinical experience a four-level model of psychogenic ED is proposed that consists of dispositional, etiologic, pathogenetic, and maintaining factors. In addition, four different pathogenetic modes of psychogenic ED are differentiated, which have been labeled actual-neurotic, psychoneurotic, psychosomatic, and functional. Conclusions concentrate on these modes as well as on the empirical subtypes and their implications for clinical practice and future research. Our results indicate that we are just beginning to understand the complex pathogenic interface between psychological factors and manifest ED.

Erectile Dysfunction↗

Lyme borreliosis and multiple sclerosis are associated with primary effusion lymphoma.

Multiple sclerosis (MS) is a chronic disease of the central nervous system characterized by chronic inflammation and demyelination. Studies suggested that the viral, especially Epstein-Barr virus infection, and bacterial infections, especially Borrelia burgdorferi infection, play a role in etiology of MS. MS prevalence parallels the distribution of the Lyme disease pathogen B. burgdorferi. Criteria used for diagnosis of MS can also be fulfilled in other conditions such as Lyme disease, a multisystem disorder resulting from infection by the tick-borne spirochete, B. burgdorferi. In the late period of Lyme disease demyelinating involvement of central nervous system can develop and MS can be erroneously diagnosed. A Lyme borreliosis can mimick central nervous system lymphoma. Also, B. burgdorferi has been implicated not only in etiology of MS, but also in etiology of lymphoma. Studies suggested that there is an increased risk of non-Hodgkin lymphoma in patients, who had a history of autoimmune diseases such as MS and that both non-Hodgkin's lymphomas and Hodgkin's disease were associated with Epstein-Barr virus infection. A small group of lymphomas called primary effusion lymphomas (PEL) is a recently individualized form of non-Hodgkin's lymphoma (WHO classification) that exhibit exclusive or dominant involvement of serous cavities, without a detectable solid tumor mass. These lymphomas have also been linked to Epstein-Barr virus and human herpes virus type 8 infections but virus negative cases have been described. Therefore, we propose that MS and neuroborreliosis are linked to central nervous system primary effusion lymphomas. As a first step in confirming or refuting our hypotheses, we suggest a thorough study of CSF in the patients suspected for the diagnosis of MS and Lyme borreliosis.

Humans↗

Characterization of streptococci and enterococci associated with septicaemia in broiler parents with a high prevalence of endocarditis.

Increased mortality due to septicaemia, where 29% of the affected birds had developed valvular endocarditis, was observed in a flock of broiler parents affected by myelocytomatosis. Bacterial investigations resulted in isolation of streptococci, the classification of which was unknown according to present taxonomy. Strains were isolated from the liver, spleen, heart and salpinx in clinical cases of septicaemia from the affected flock of Ross broiler parents aged between 26 and 56 weeks. Phenotypic characterization followed by genotypic investigation by ribotyping with HindIII and pulsed-field gel electrophoresis (PFGE) with SmaI demonstrated three ribotypes and six different PFGE profile types, respectively. Ribotype A with variant A1, together with the PFGE profile type represented by the three subtypes Ia, Ib and Ic, dominated the outbreak constituting 85% of the strains investigated, indicating clonality. 16S rRNA sequencing of strains representing this genotype demonstrated the occurrence of a recently described new Streptococcus sp., Streptococcus gallinaceus. Sequence analysis of the other genotypes demonstrated in the outbreak, resulted in identical 16S rRNA sequences to the type strain of Enterococcus faecalis. S. gallinaceus appears to represent a new opportunistic pathogen within the poultry industry.

Animals↗

Hantavirus pulmonary syndrome in Latin America.

PURPOSE OF REVIEW: Since the identification of hantavirus pulmonary syndrome in the United States in 1993, Latin America has been the region of the world where more hantaviruses have been identified, associated with human disease or not. This update shows the advances in the study of hantaviruses in several countries of the region and the problems that are still unresolved. RECENT FINDINGS: Clinical findings in Chile have shown differences in the classical description of hantavirus pulmonary syndrome in the United States. Hemorrhage was observed in 64% of the cases and alteration in renal function in 48%. The classification of cases in mild, self-limited forms and severe forms has a prognostic value, with statistically significant differences between survivors and nonsurvivors. Epidemiological studies have shown noticeable differences in seroprevalence of antibodies against hantaviruses in humans, ranging from about 1% to more than 40% according to geographical and ethnical differences. Risk factors continue to be related to rural activities and peridomestic sites. Rodent studies have allowed the identification of putative reservoirs of hantaviruses in Uruguay, Brazil and Argentina and detected antibodies in several rodent species not previously reported in Paraguay and Panama. An Andes virus gene-based hantavirus pulmonary syndrome vaccine is currently under study. SUMMARY: Progress in research on hantaviruses has been continuous but slow. The complex picture of the viruses, the rodent reservoirs and the clinical forms of the disease mean researchers are faced with the great challenge of properly clarifying the genetic and pathogenic relationships between hantaviruses in the Americas.

Animals↗

Prevalence of Serpulina species in relation to diarrhea and feed medication in pig-rearing herds in Sweden.

OBJECTIVE: To determine prevalence of various pheno- and genotypes of Serpulina sp in young pigs in relation to diarrhea and feed medication in Swedish pig-rearing herds. DESIGN: Isolation of spirochetes. Phenotypical and genotypical classification. SAMPLE POPULATION: Young pigs (n = 358) in 19 pigrearing herds. PROCEDURE: Serpulina isolates were classified according to a biochemical scheme based on hemolysis, indole production, hippurate hydrolysis, and alpha-galactosidase, alpha-glucosidase, and beta-glucosidase activities. The 16S rRNA sequences for 10 of the field strains and 2 type strains of Serpulina spp were aligned and compared. Minimum inhibitory concentrations of olaquindox for 9 of the strains were determined. RESULTS: Weakly beta-hemolytic intestinal spirochetes (WBHIS) were isolated from 17 of the herds and 65% of the samples. More than 1 phenotype of WBHIS was found in 12 of the 19 herds. S hyodysenteriae was not isolated in any of the herds. Hippurate-positive WBHIS were isolated in 6 of 7 herds affected by diarrhea, but in only 1 of 8 herds without diarrhea. Hippurate-positive strains were closely related to the pathogenic strain P43 if judged from sequence comparisons. Strains with the same biochemical profile isolated within a herd had identical sequences, but when isolated from different herds, sequence differences were observed. The prevalence of WBHIS was reduced in herds medicated with olaquindox. Investigated field strains had minimum inhibitory concentration values < or = 1 microgram/ml for olaquindox. CONCLUSION: The presence of WBHIS, with the ability to hydrolyze hippurate, was related to diarrhea in pig herds. CLINICAL RELEVANCE: Potentially pathogenic WBHIS can be distinguished from nonpathogenic strains by the hippurate hydrolysis test.

Animal Feed↗

Analysis of surface proteins of Listeria in relation to species, serovar and pathogenicity.

SDS extracts of whole bacteria, representing five species and 15 serovars of Listeria, were analysed by SDS-PAGE and by immunoblotting with serum directed against whole formalin-treated L. monocytogenes. Profiles of L. monocytogenes were very different from those of other species of Listeria (i.e. L. innocua,L.welshimeri, L. seeligeri and L. ivanovii). This low degree of similarity between species was found even in the case of common serovars. Within the species L. monocytogenes, protein patterns were characterized, on the one hand, by a high degree of homogeneity between all strains of the same serovar and, on the other hand, by large differences between serovars, especially between sv. 1/2 and 4b. Thus we have identified major, surface-located protein antigens, specific for L. monocytogenes, either common to all serovars (64 and 68 kDa) or characteristic of certain serovars: 98 kDa for sv. 1/2 and 3; 76 and 78 kDa for sv. 4b, 4d and 4e; and 80 and 100 kDa for sv. 4a and 4c. Moreover, some of these bands (68 and 98 kDa) might be related to virulence, since differences were noticed between the profiles of haemolytic L. monocytogenes vs. 1/2a differing only in their virulence for immunocompromised mice. All these results confirmed, for the first time, the classification of Listeria obtained previously by genomic studies. They should help in the identification of new virulence factors and the development of easier and more specific methods of detection and identification.

Antigens, Bacterial↗

Crossroads of B cell activation in autoimmunity: rationale of targeting B cells.

B cells have historically been considered as not preferentially involved in the immunopathogenesis of inflammatory joint diseases, in particular rheumatoid arthritis (RA), despite the notion that autoantibodies and immune complexes were involved in pathogenesis and served as diagnostic and classification markers. Following initial reports that patients with non-Hodgkin's lymphoma (NHL) and coexisting RA showed improvement in signs and symptoms of RA after anti-CD20 therapy, the role of B cells in autoimmune diseases was reexamined. Potential mechanisms can be inferred from what is known about the role of B cell functions, in particular antigen-experienced memory B cells. Activation of these cells can be dependent on T lymphocytes or independent of them. Once activated, the cells can efficiently act as antigen-presenting cells, can produce inflammatory cytokines, and may alternatively differentiate into antibody-producing plasma cells. These processes contribute to the activation of other immune cells and ultimately to joint destruction in RA. The development and maintenance of RA may be related to both direct and indirect involvement of these B cell-dependent processes. In systemic lupus erythematosus (SLE), the central pathogenic importance of autoimmune B cells is well recognized, based on early recognition of numerous autoantibodies and clinically important immune complexes. Based on the evidence supporting B cell involvement in the pathophysiology of autoimmune diseases, investigations are evaluating the clinical impact of B cell targeted therapies. B cell targeted therapies in human trials include an anti-B lymphocyte stimulator protein agent, belimumab; an anti-CD20 agent, rituximab; and an anti-CD22 antibody, epratuzumab.

Animals↗

[Salmonella: its incidence in waters of the Zaimán arroyo].

The present work is the initial stage of a project to determine the causes and degree of pollution of the Zaiman creek waters, which flow through wide suburban areas of Posadas, Argentina. The research was focused on the presence of Salmonella serotypes, pathogenic microorganisms probably responsible for most waterborne disease outbreaks. In addition, the N.M.P./100 ml (Most Probable Number) of total coliform organisms was determined in samples collected from points near cold storage plant and slaughterhouse, both to show the pollution effect of industrial discharges. So far, 35 sampling operations have been carried out in representative geographic points. The methodology for Salmonella consisted in applying concentration technics for waterborne pathogens, followed by an enrichment procedure performed by incubating samples in Dulcitol Selenite and Tetrathionate (Muller-Kauffman) broths at 41.5 degrees C during 25 hours. Typical, well-isolated Salmonella-like colonies were obtained by streaking duplicate plates of E.M.B. Agar (Eosin Methylene Blue), Brilliant Green Agar and Bismuth Sulphite Agar. Suspected colonies were classified by 10 biochemical reactions and further verified by serological identification, performed at the National Institute of Microbiology "Carlos Malbrán". The methodology followed for the determination of total coliforms was the one described in the American Water Standards. Salmonella serotypes were isolated in 46% of the examined samples. Isolation efficiency of culture media is shown. First isolations of Salmonella abaetetuba and S. saphra are reported. Most serotypes were isolated from sampling points down-stream from the industrial plant. Zaimán creek waters were classified as No 4 of W.H.O (World Health Organization) stream waters classification, except during heavy rain periods in which they ranked as No 3.

Abattoirs↗

Hemophagocytic lymphohistiocytosis. Report of 122 children from the International Registry. FHL Study Group of the Histiocyte Society.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, often fatal, disease of early infancy. The diagnosis of HLH is frequently delayed or made at autopsy because no genetic or biologic marker has been identified. To improve the classification and treatment of HLH, the Histiocyte Society has established an 'International Registry for HLH'. Data collected included family history, clinical and laboratory features at the onset of illness, and treatment outcome. Stringent diagnostic criteria (ie fever, splenomegaly, cytopenia, hypertriglyceridemia, and/or hypofibrinogenemia, and hemophagocytosis without evidence of malignancy) were used for patient selection. One hundred and twenty-two patients (61 males, 61 females) were enrolled from 17 centers in 11 countries. The rate of parental consanguinity was 24%. A positive family history was reported in 49% of cases including two pairs of affected male twins. The median age at disease onset was 2.9 months, with no difference between familial and sporadic cases. Age at onset was similar in affected sibs from 10 of 14 families, but in four up to 3-year differences were observed. Hemophagocytosis was present at diagnosis in 75%. An associated infection (usually by common viral pathogens) was reported in 50 of the 122 (41%) cases, of which 25 had familial disease. Natural killer activity was impaired in 36 of 37 patients studied. Chromosome analysis was normal in all tested patients. A decreased frequency of HLA-B7 and B8 alleles and increased frequency of HLA-B21 and DQ3 were observed. The estimated 5-year survival (SE) was 21% (18.7) for all patients. It was 66% (37.8) for patients who received allogeneic bone marrow transplant and 10.1% (9.6) for patients treated with chemotherapy alone (P=0.0001). None of the previously proposed prognostic indicators (age, associated infection, cerebrospinal fluid pleocytosis, family history) correlated with treatment outcome.

Age of Onset↗

Successful cultivation of a potentially pathogenic coccoid organism with trophism for gastric mucin.

We have devised a procedure that permits the cultivation of a gram-positive coccoid species from biopsy material obtained from the antrum of the stomachs of patients with gastric disorders. Antibodies directed against surface proteins obtained from the coccoid isolates were detected in all patients with gastric disorders examined in this study, including both Helicobacter pylori-infected and H. pylori-uninfected patients. Several of these isolates, including a prototype designated strain SL100, have been characterized in some detail. Strain SL100 exhibits urease and exceptionally high catalase activities and assumes a variety of spherical morphologies as detected by electron microscopy. This isolate expresses an adhesin that binds to gastric mucin. The adhesin activity was detected only after the isolate was exposed to an acidic pH, suggesting that in the natural process of infection, the low pH of the stomach unmasks a cell surface component with adhesin activity. Strain SL100 grows best under a microaerophilic conditions (10% CO2, 5% O2, 85% N2), but it also grows quite well under aerobic conditions. Thus, this organism would be expected to proliferate outside of the human host as well as in the gastric mucosa. Oral infection of newborn piglets resulted in colonization of the gastric antrum and growth retardation. Preliminary taxonomic classification indicates similarity to the Staphylococcus DNA homology groups containing S. cohnii and S. xylosus. One of us (C.K.) apparently became infected with this organism as indicated by gastric symptoms and the subsequent presence of strain-specific antisera not present in other workers in the laboratory.

Adult↗