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Malignant vascular tumors of the serous membranes mimicking mesothelioma. A report of 14 cases.

Malignant endothelial neoplasms involving the serous membranes are rare, and only a few cases have been documented. We report 14 patients with epithelioid hemangioendothelioma (EHE) or epithelioid angiosarcoma (EA) diffusely involving the pleural, peritoneal, or pericardial cavities, resulting in a picture closely resembling mesothelioma. The mean age at diagnosis was 52 (range, 34-85). The patients included two women and one man with peritoneal tumors, eight men with pleural tumors, and three men with pericardial tumors. A shared histological appearance was a diffuse sheet-like and clustered pattern of tumor growth with variable degrees of vascular differentiation. A tubulopapillary growth pattern, often seen in mesothelioma, was prominent in four cases. Nine cases showed a variable number of spindle cells, some neoplastic, others reactive, focally producing a biphasic growth pattern, further suggesting mesothelioma. Initial interpretations included mesothelioma, adenocarcinoma, and, in one case with prominent spindle-cell components, leiomyosarcoma. Immunohistochemically, strong vimentin staining and negative or weak to moderate cytokeratin staining were observed in all 14 cases. The tumor cells coexpressed at least two of the four endothelial markers used in the study (CD31, CD34, von Willebrand factor, and Ulex europaeus agglutinin-I [UEA-I)]. Detection of abortive vessel formation was facilitated by staining for collagen type IV. Markers of mesothelial, epithelial, muscular, and neuronal differentiation were all negative in the subset of cases studied. As a control group, 39 mesotheliomas and more than 60 adenocarcinomas of various origins were studied using the same antibody panel. This group revealed strong keratin staining, moderate or negative vimentin staining, and no expression of any of the endothelial-lineage markers, with the exception of positive staining for UEA-I in occasional adenocarcinomas. Clinically, these endothelial tumors were highly aggressive; 12 patients presented with disseminated disease, and most died within months of the initial presentation. These findings indicate that, although uncommon, EHE/EA should be included in the differential diagnosis of serous membrane neoplasms with histological and clinical features of malignant mesothelioma. The diagnosis of an endothelial neoplasm can be suspected by the presence of abortive vessel formation and by the strong expression of vimentin, with absent or low-level expression of cytokeratin. The demonstration of immunoreactivity for two or more endothelial-associated markers is essential in confirming the diagnosis.

Adult↗

Do needle exchange programmes increase the spread of HIV among injection drug users?: an investigation of the Vancouver outbreak.

OBJECTIVE: An association between needle exchange attendance and higher HIV prevalence rates among injecting drug users (IDU) in Vancouver has been interpreted by some to suggest that needle exchange programmes (NEP) may exacerbate HIV spread. We investigated this observed association to determine whether needle exchange was causally associated with the spread of HIV. DESIGN AND METHOD: Prospective cohort study of 694 IDU recruited in the downtown eastside of Vancouver. Subjects were HIV-negative at the time of recruitment and had injected illicit drugs within the previous month. RESULTS: Of 694 subjects, the 15-month cumulative HIV incidence was significantly elevated in frequent NEP attendees (11.8+/-1.7 versus 6.2+/-1.5%; log-rank P = 0.012). Frequent attendees (one or more visits per week) were younger and were more likely to report: unstable housing and hotel living, the downtown eastside as their primary injecting site, frequent cocaine injection, sex trade involvement, injecting in 'shooting galleries', and incarceration within the previous 6 months. The Cox regression model predicted 48 seroconversions among frequent attendees; 47 were observed. Although significant proportions of subjects reported obtaining needles, swabs, water and bleach from the NEP, only five (0.7%) reported meeting new friends or people there. When asked where subjects had met their new sharing partners, only one out of 498 respondents cited the needle exchange. Paired analysis of risk variables at baseline and the first follow-up visit did not reveal any increase in risk behaviours among frequent attendees, regardless of whether they had initiated drug injection after establishment of the NEP. CONCLUSIONS: We found no evidence that this NEP is causally associated with HIV transmission. The observed association should not be cited as evidence that NEP may promote the spread of HIV. By attracting higher risk users, NEP may furnish a valuable opportunity to provide additional preventive/support services to these difficult-to-reach individuals.

Adult↗

The significance and measurement of head position during speech production experiments using the x-ray microbeam system.

Head position and orientation are important variables during experiments conducted on the University of Wisconsin x-ray microbeam system, a nationally shared imaging facility for speech production research. Normally, the head is not restrained during experiments, in order to maximize the naturalness of speech performance, even though free head movements may have an adverse effect on the accuracy of kinematic data that are obtained. The basis for this effect is explained, and techniques for dealing with temporal variations in head position are described. Results obtained from a novel method for three-dimensional measurement of head position, applied to data sets recorded from six normal adult speakers during otherwise typical x-ray microbeam experiments, are summarized to convey some sense of the measurement error that can arise from deviations from a required head position. These measurements suggested that among these speakers, errors attributable to improper positioning of the head, and/or inadvertent head movements within or between trials, never exceeded 5%.

Computer Graphics↗

Cellulose synthase (CesA) genes in the green alga Mesotaenium caldariorum.

Cellulose, a microfibrillar polysaccharide consisting of bundles of beta-1,4-glucan chains, is a major component of plant and most algal cell walls and is also synthesized by some prokaryotes. Seed plants and bacteria differ in the structures of their membrane terminal complexes that make cellulose and, in turn, control the dimensions of the microfibrils produced. They also differ in the domain structures of their CesA gene products (the catalytic subunit of cellulose synthase), which have been localized to terminal complexes and appear to help maintain terminal complex structure. Terminal complex structures in algae range from rosettes (plant-like) to linear forms (bacterium-like). Thus, algal CesA genes may reveal domains that control terminal complex assembly and microfibril structure. The CesA genes from the alga Mesotaenium caldariorum, a member of the order Zygnematales, which have rosette terminal complexes, are remarkably similar to seed plant CesAs, with deduced amino acid sequence identities of up to 59%. In addition to the putative transmembrane helices and the D-D-D-QXXRW motif shared by all known CesA gene products, M. caldariorum and seed plant CesAs share a region conserved among plants, an N-terminal zinc-binding domain, and a variable or class-specific region. This indicates that the domains that characterize seed plant CesAs arose prior to the evolution of land plants and may play a role in maintaining the structures of rosette terminal complexes. The CesA genes identified in M. caldariorum are the first reported for any eukaryotic alga and will provide a basis for analyzing the CesA genes of algae with different types of terminal complexes.

Algal Proteins↗

Streptococcus pyogenes type 12 M protein gene regulation by upstream sequences.

A partial nucleotide sequence that included 1,693 base pairs of the M12 (emm12) gene of group A streptococci (strain CS24) and adjacent upstream DNA was determined. Type 12 M protein-specific mRNA of strain CS24 is transcribed from two promoters (P1 and P3) separated by 30 bases. The transcription start sites of the emm12 gene were located more than 400 bases downstream of a deletion that causes decreased M-protein gene transcription in strain CS64. Deletion analysis of M protein-expressing plasmids indicated that an upstream region greater than 1 kilobase is required for M-protein gene expression. The M-protein gene transcriptional unit appears to be monocistronic. Analysis of the emm12 DNA sequence revealed three major repeat regions. Two copies of each repeat, A and B, existed within the variable 5' end of the gene; repeat C demarcated the 5' end of the constant region shared by emm12 and emm6.

Antigens, Bacterial↗

Mitochondrial functions in five cases of human neuromuscular disorders.

We determined the respiration, respiratory control, and Pi:O ratios with different substrates in mitochondria isolated from five cases of human neuromuscular disorders (two cases of central core disease, two cases of neuropathy of Dejerine-Sottas, and one case of Kugelberg-Welander's disease) and compared them with normal human muscle. In all the myopathies studied, a severe derangement of the respiratory control with variable derangement of oxidative phosphorylation was found. This supports the idea that a group of neuromyopathies shares the same biochemical lesion as the so-called mitochondrial myopathies, forming with them a group of myopathies which may be related through a similar biochemical lesion of varying degree. Alternatively, disturbance of mitochondrial functions in a number of myopathies could be considered as a non-specific finding.

Adenosine Diphosphate↗

Management of antenatally diagnosed pulmonary sequestration associated with congenital cystic adenomatoid malformation.

BACKGROUND: Sequestration with associated cystic adenomatoid malformation is rare. A study was undertaken to determine whether pulmonary sequestration associated with congenital cystic adenomatoid malformation has a more favourable natural history than that of sequestration without associated cystic adenomatoid malformation. METHODS: An outline of the postnatal work up leading to the management of extralobar or intralobar pulmonary sequestration with congenital cystic adenomatoid malformation diagnosed antenatally as pulmonary malformation is presented and the indications for surgical intervention are discussed. RESULTS: In five infants in whom an antenatal ultrasound scan had detected a congenital lung malformation at 18-19 weeks gestation a final diagnosis of extralobar or intralobar pulmonary sequestration with congenital cystic adenomatoid malformation was made postnatally. Postnatal ultrasound and computerised axial tomographic scans confirmed the diagnosis of sequestration by delineating anomalous vascular supply. Cystic changes were also observed in the basal area of the sequestration in all patients. Four children remained asymptomatic and one infant presented at 10 months of age with pneumonia. The mean age at surgical resection was 6.8 months (range 2-10). Histopathological examination confirmed intralobar pulmonary sequestration with associated Stocker type 2 congenital cystic adenomatoid malformation in two patients and extralobar pulmonary sequestration with associated Stocker type 2 congenital cystic adenomatoid malformation in three patients. The mean period of follow up was four years (range 1-8). The children remain well and are developing normally. CONCLUSIONS: The importance of seeking an anomalous blood supply in children with congenital lung lesions is emphasised. Pulmonary sequestration and congenital cystic adenomatoid malformation probably share a common embryogenesis despite diverse morphology. The natural history of antenatally diagnosed lung masses is variable. Early postnatal surgical resection of pulmonary sequestration with cystic adenomatoid malformation is recommended. Surgical excision should be conservative, sparing the normal lung parenchyma.

Adenoma↗

Interim report on genomics of Escherichia coli.

We present a summary of recent progress in understanding Escherichia coli K-12 gene and protein functions. New information has come both from classical biological experimentation and from using the analytical tools of functional genomics. The content of the E. coli genome can clearly be seen to contain elements acquired by horizontal transfer. Nevertheless, there is probably a large, stable core of >3500 genes that are shared among all E. coli strains. The gene-enzyme relationship is examined, and, in many cases, it exhibits complexity beyond a simple one-to-one relationship. Also, the E. coli genome can now be seen to contain many multiple enzymes that carry out the same or closely similar reactions. Some are similar in sequence and may share common ancestry; some are not. We discuss the concept of a minimal genome as being variable among organisms and obligatorily linked to their life styles and defined environmental conditions. We also address classification of functions of gene products and avenues of insight into the history of protein evolution.

Chromosomes, Bacterial↗

Isotypic analysis of grass pollen-specific immunoglobulins in human plasma. 1. Specialization of certain classes and subclasses in the immune response.

The specificity and isotypic profile of humoral immune responses to Dactylis glomerata (Cocksfoot) pollen was studied by isoelectric focusing (IEF)-immunoprint analysis using 26 human plasma samples with high levels of Dactylis pollen-specific IgG4 (IgG4+ plasma) and 25 human plasma samples with low levels of specific IgG4 (normal plasma). Over 60 individual protein components in an aqueous pollen extract were separated by IEF and immunoprinted onto nitrocellose (NC). Following plasma incubation, bound IgE, IgG1-4, IgA1, IgA2 and IgM antibodies were detected on separate immunoprints with isotype-specific antibodies. Binding patterns of IgG4 and the majority of IgG1 and IgA2 antibodies in the IgG4+ plasma group very closely paralleled the binding patterns produced by the IgE antibodies from the same plasma and are described as the 'allergen repertoire'. In contrast, IgE, IgG4, IgG1 and IgA2 antibody reactivities to the 'allergen repertoire' were insignificant in the normal plasma group. These results suggest a qualitative, as well as a quantitative relationship between the immune responses which involve these 4 isotypes. Characteristic IgG2 and IgM antibody binding patterns, predominantly to non-allergenic antigens, were shared by the plasma from both groups, while IgG3 and IgA1 antibody binding patterns were highly variable from one plasma to another in both groups. One possible origin of the allergic diseases at the immunoglobulin heavy chain gene level is discussed.

Antibody Formation↗

Small, dense LDL and elevated apolipoprotein B are the common characteristics for the three major lipid phenotypes of familial combined hyperlipidemia.

OBJECTIVE: Familial combined hyperlipidemia (FCHL) is associated with variable lipid and lipoprotein phenotypes arbitrarily defined as type IIa, IIb, and IV based on plasma total cholesterol and triglyceride levels. This study sought to characterize consistent lipoprotein and lipid abnormalities across the 3 lipoprotein phenotypes in 62 patients with documented FCHL (IIa [n=14], IIb [n=19], and IV [n=29]) and 44 healthy individuals. METHODS AND RESULTS: The lipoprotein cholesterol distribution was determined over 38 fractions obtained by density gradient ultracentrifugation. As expected, FCHL patients with hypertriglyceridemia (IIb and IV) had higher cholesterol levels in VLDL than IIa, whereas IIa showed higher cholesterol in the big, buoyant LDL and in HDL. LDL cholesterol was higher in IIb than IV; most of the increase in LDL cholesterol was associated with big, buoyant LDL rather than small, dense LDL (sdLDL). The differences in lipoproteins between phenotypes were attributable to changes in VLDL and big, buoyant LDL levels. Comparison of the FCHL patients with healthy individuals showed a significant elevation in plasma apolipoprotein B levels and sdLDL in all 3 FCHL phenotypes. CONCLUSIONS: Although triglyceride and cholesterol levels are variable by lipoprotein phenotype, sdLDL and elevated plasma apolipoprotein B levels are consistent characteristics of FCHL shared by the 3 different lipoprotein phenotypes.

Adult↗

Formin homology 2 domains occur in multiple contexts in angiosperms.

BACKGROUND: Involvement of conservative molecular modules and cellular mechanisms in the widely diversified processes of eukaryotic cell morphogenesis leads to the intriguing question: how do similar proteins contribute to dissimilar morphogenetic outputs. Formins (FH2 proteins) play a central part in the control of actin organization and dynamics, providing a good example of evolutionarily versatile use of a conserved protein domain in the context of a variety of lineage-specific structural and signalling interactions. RESULTS: In order to identify possible plant-specific sequence features within the FH2 protein family, we performed a detailed analysis of angiosperm formin-related sequences available in public databases, with particular focus on the complete Arabidopsis genome and the nearly finished rice genome sequence. This has led to revision of the current annotation of half of the 22 Arabidopsis formin-related genes. Comparative analysis of the two plant genomes revealed a good conservation of the previously described two subfamilies of plant formins (Class I and Class II), as well as several subfamilies within them that appear to predate the separation of monocot and dicot plants. Moreover, a number of plant Class II formins share an additional conserved domain, related to the protein phosphatase/tensin/auxilin fold. However, considerable inter-species variability sets limits to generalization of any functional conclusions reached on a single species such as Arabidopsis. CONCLUSIONS: The plant-specific domain context of the conserved FH2 domain, as well as plant-specific features of the domain itself, may reflect distinct functional requirements in plant cells. The variability of formin structures found in plants far exceeds that known from both fungi and metazoans, suggesting a possible contribution of FH2 proteins in the evolution of the plant type of multicellularity.

Actins↗

Prostate size and risk of high-grade, advanced prostate cancer and biochemical progression after radical prostatectomy: a search database study.

PURPOSE: Prostate growth and differentiation are under androgenic control, and prior studies suggested that tumors that develop in hypogonadal men are more aggressive. We examined whether prostate weight was associated with tumor grade, advanced disease, or risk of biochemical progression after radical prostatectomy (RP). PATIENTS AND METHODS: We evaluated the association of prostate weight with pathologic tumor grade, positive surgical margins, extracapsular disease, and seminal vesicle invasion using logistic regression and with biochemical progression using Cox proportional hazards regression among 1,602 men treated with RP between 1988 and 2003 at five equal-access medical centers, which composed the Shared Equal Access Regional Cancer Hospital (SEARCH) Database. RESULTS: In outcome prediction models including multiple predictor variables, it was found that the predictor variable of prostate weight was significantly inversely associated with the outcomes of high-grade disease, positive surgical margins, extracapsular extension (all P < or = .004), and biochemical progression (comparing prostate weight < 20 v > or = 100 g: relative risk = 8.43; 95% CI, 2.9 to 24.0; P < .001). Similar associations were seen between preoperative transrectal ultrasound-measured prostate volume and high-grade disease, positive surgical margins, extracapsular extension (all P < or = .005), seminal vesicle invasion (P = .07), and biochemical progression (P = .06). CONCLUSION: Men with smaller prostates had more high-grade cancers and more advanced disease and were at greater risk of progression after RP. These results suggest that prostate size may be an important prognostic variable that should be evaluated for use pre- and postoperatively to predict biochemical progression.

Humans↗

Proteins with spectrin motifs which do not belong to the spectrin-alpha-actinin-dystrophin family.

Using several consensus sequences for the 106 amino acid residue alpha-spectrin repeat segment as probes we searched animal sequence databases using the BLAST program in order to find proteins revealing limited, but significant similarity to spectrin. Among many spectrins and proteins from the spectrin-alpha-actinin-dystrophin family as well as sequences showing a rather high degree of similarity in very short stretches, we found seven homologous animal sequences of low overall similarity to spectrin but showing the presence of one or more spectrin-repeat motifs. The homology relationship of these sequences to alpha-spectrin was further analysed using the SEMIHOM program. Depending on the probe, these segments showed the presence of 6 to 26 identical amino acid residues and a variable number of semihomologous residues. Moreover, we found six protein sequences, which contained a sequence fragment sharing the SH3 (sarc homology region 3) domain homology of 42-59% similarity. Our data indicate the occurrence of motifs of significant homology to alpha-spectrin repeat segments among animal proteins, which are not classical members of the spectrin-alpha-actinin-dystrophin family. This might indicate that these segments together with the SH3 domain motif are conserved in proteins which possibly at the early stage of evolution were close cognates of spectrin-alpha-actinin-dystrophin progenitors but then evolved separately.

Actinin↗

Variations in venous and segmental anatomy of the liver: two- and three-dimensional MR imaging in healthy volunteers.

OBJECTIVE: The purpose of this study was to use two- and three-dimensional analysis of thin-slice MR imaging data to study the anatomic variations in the segmental anatomy of the liver. It is important to recognize these anatomic variations in order to ensure accurate localization of hepatic lesions and preoperative delineation of resection planes. SUBJECTS AND METHODS: T1-weighted MR images of contiguous 4-mm sections were obtained in 10 healthy subjects. We measured the orientations of external and internal hepatic landmarks that indicated segmental boundaries and created three-dimensional renderings of hepatic veins, intrahepatic portal branches, liver surface, and gallbladder. RESULTS: Variations in the portal branching pattern were seen in eight of 10 subjects. Most variations occurred in the right hemiliver and consisted of the absence of a right portal trunk or the presence of accessory portal branches. The division between right anterior and right posterior segments was inclined posteriorly (average, 31.2 degrees) relative to the right hepatic vein. The landmarks indicating the position of the umbilical fissure showed marked variability. Only two of 10 subjects had three hepatic veins, with the left and middle veins sharing a common trunk. In the remaining eight subjects, nine accessory veins were present: three left, one middle, and five right. CONCLUSION: Planes of resection in liver surgery are largely determined by the precise position of tumor relative to the individual segmental anatomy. Consequently, localization of liver lesions and preoperative delineation of resection planes requires consideration of the significant anatomic variations in the segmental anatomy of the liver. These anatomic variations can be depicted on two- and three-dimensional displays of T1-weighted MR images of contiguous 4-mm sections.

Adult↗

Social desirability and self-reports of mood: a rejoinder.

Warehime and Jones found moderate correlations between social desirability and short-term mood level scores on the Wessman-Ricks Personal Feeling Scales. They suggested that it might be valuable to study patterns of dissimulation in self-reports of immediate feeling states. In the present authors' studies involving long-term mood reports and multivariate methods, social desirability was shown to have a moderately weak relationship with measures of mood level and mood variability. Under conditions of confidentiality and good rapport, repeated self-reports of mood appeared to share more variance with important personality characteristics and situational influences than with social desirability per se.

Emotions↗

A new name for Torula glutinosa in Heteroconium.

Torula glutinosa, a sooty mold on living leaves and stems of Eriodictyon spp. from California is illustrated and described. It shares, with the type species of Heteroconium, H. citharexyli, acropetal conidiogenesis of chains of conidia of variable length and acropetal transseptation. An unnamed synanamorph is recognized and described.

Ascomycota↗

[Anger experience and the process of calming down].

This study investigated the affects and behaviors that accompany and follow anger episodes, and examined the relationship among them, in hope of developing self-regulated and effective methods of controlling anger. With an open-ended questionnaire, 42 anger episodes were collected and categorized. Results suggested that typical anger episodes were instigated by selfishness, insult, coercion, and trouble and a close person such as friends was often the cause and target of anger. Surprise and depression frequently accompanied it, and eight forms of response followed: rationalization, cause searching, aggression, social sharing, displacement to object, mood change, forgetfulness, and rumination. Another questionnaire examined the relationship among these variables, as well as trait anger, perception of malice, and sense of injury, with a sample of 118 undergraduates. Results indicated, first, that sense of injury was heightened by trait anger and malice perception. Second, anger and depression were evoked only by a sense of injury. Finally, while anger without depression evoked aggression, anger with depression led to mood change and forgetfulness.

Adult↗

The implications of TRICARE on medical readiness.

The objective of this study was to compare two alternative sources of replacement personnel for a medical treatment facility experiencing personnel loss due to a deployment. The two replacement strategies included the reserve component option and the TRICARE internal resource-sharing option. A hypothetical scenario was used as a mechanism for the analysis, and three key variables were considered: effectiveness, feasibility, and operational expense. From the perspective of effectiveness, the TRICARE strategy demonstrated an ability to provide a slightly larger percentage of the requested replacement personnel. With regard to feasibility, both strategies were feasible in that both could provide replacements for the duration of the 270-day deployment and within an established 180-day report date. Operational expense was a decisive factor with the reserve component option significantly less costly than the TRICARE alternative. Weaknesses and strengths of each option were identified and discussed, and alternatives were recommended.

Employee Incentive Plans↗