Vascular malformations of the central nervous system.
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Arteriovenous Malformations↗
Biomedical subjects
W R Brown
Publications and source records attributed to W R Brown.
Periventricular venous collagenosis: association with leukoaraiosis.
PURPOSE: To investigate the association between an age-related degenerative disease of subependymal veins and leukoaraiosis. MATERIALS AND METHODS: Brains obtained at autopsy from 22 patients (average age, 73.2 years; range, 25-95 years) were examined with magnetic resonance (MR) imaging and neuropathologic methods with alkaline phosphatase microvascular staining. The degrees of leukoaraiosis shown on MR images and of deep venous occlusion were scored independently and results compared with logistic regression analysis. RESULTS: Noninflammatory collagenous thickening of venous walls resulting in severe periventricular venous stenosis was found in 13 (65%) of 20 patients over 60 years old. Advanced leukoaraiosis was found in 10 (77%) of these 13 patients. Greater venous disease was associated with more severe leukoaraiosis. CONCLUSION: Periventricular venous collagenosis, a commonly observed and previously ignored degenerative disease of elderly humans, is strongly associated with leukoaraiosis. Stenosis or occlusion of deep cerebral veins may promote development of leukoaraiosis.
Adult↗
Brain slice holder for MR.
We made an MR-compatible brain slice holder that ensures that the images have the same location and orientation as the subsequent histologic sections. This device encloses the unfixed tissues, thus reducing the danger of exposure to pathogens. MR imaging time is saved by scanning selected slices rather than the whole brain; this technique is especially useful when brain sections at varying angles, rather than parallel slices, are taken.
Brain↗
Expressed swine VH genes belong to a small VH gene family homologous to human VHIII.
The sequences of 34 swine H chain V-regions expressed with either IgG, IgA, or IgM C regions in adult swine and newborn piglets are described and compared. Sixteen of these V-regions were cloned by using a specific leader primer whereas 18 were cloned by anchored PCR. According to the operational criterion of VH family classification, i.e., > 80% DNA sequence similarity, all sequences belong to a homogeneous VH gene family. A total of 31 additional VH-bearing C mu clones obtained by anchored PCR from colostrum-deprived newborn piglets hybridized equally with a probe for C mu and a pan-VH probe. When the consensus sequence of the expressed swine VH genes were compared with those of VH gene for humans (VHI, II, III), mouse (VHI, II, III), rabbit, and chicken, swine VH genes seem to have common ancestry with the human VHIII family, rabbit VH genes, and the single functional VH gene of the chicken. The leader peptides of all clones obtained by anchored PCR showed < 1% variability, and the deduced amino acid sequences from aa4 to aa25 in all 34 clones are identical. Framework (FR)1 and FR2 are conserved whereas FR3 shows greater variability. A total of 23 of 30 JH sequences were identical, suggesting preferential use of one JH. This frequent, putative JH sequence is not similar to any JH gene in humans. Identical genomic Southern hybridization patterns, each with 13 bands of differing intensity and regardless of stringency, were obtained when either a leader or a pan-specific VH probe was used. Analyses of individual genomic bands by single strand conformational polymorphism and sequence analysis suggest that the number of VHIII-related genes in the swine genome is < 20.
Amino Acid Sequence↗
Infrared end-tidal CO2 measurement does not accurately predict arterial CO2 values or end-tidal to arterial PCO2 gradients in rabbits with lung injury.
End-tidal PCO2 (PETCO2) measurements from two commercially available neonatal infrared capnometers with different sampling systems and a mass spectrometer were compared with arterial PCO2 (PaCO2) to determine whether the former could predict the latter in mechanically ventilated rabbits with and without lung injury. The effects of tidal volume, ventilator frequency and type of lung injury on the gradient between PETCO2 and PaCO2 (delta P(a-ET)CO2) were evaluated. Twenty rabbits were studied: 10 without lung injury, 5 with saline lavage and 5 with lung injury by meconium instillation. Paired measurements of PETCO2 by two infrared capnometers and a mass spectrometer were compared to PaCO2. In the rabbits without lung injury, the values from the infrared capnometers and mass spectrometer correlated strongly with PaCO2 (r > or = 0.91) despite differences in the slopes of the linear regression between PETCO2 and PaCO2 and in delta P(a-ET)CO2 (P < 0.05). Values from the mainstream IR-capnometer more closely approximated the line of identity than the regression between the sidestream IR-capnometer values or the mass spectrometer and PaCO2, but tended to overestimate PaCO2. The delta P(a-ET)CO2 was similar at all tidal volumes and ventilator frequencies, regardless of capnometer type. In the rabbits with induced lung injury, while there was a positive correlation between the slopes of the regression between PETCO2 and PaCO2 for both capnometers (r > or = 0.70), none of the regression slopes approximated the line of identity. The delta P(a-ET)CO2 was greater in rabbits with injured than noninjured lungs (P < 0.05). The delta P(a-ET)CO2 was similar among capnometers regardless of tidal volume, ventilator frequency, or type of lung injury. The 95% confidence interval of plots PaCO2 against PETCO2 was large for rabbits with injured and noninjured lungs.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Study of colonic IgG Fc binding site in cultured epithelial cells.
Previously, we identified a unique binding site for the Fc region of IgG in goblet cells of the human small intestine and colon. Understanding of the regulation and biological role of the binding site would be enhanced if it could be studied in cultured cells. Thus, we now have searched colonic carcinoma cell lines for presence of the site and further characterized it in such cells. HT29 and HT29-18N2 (a mucin-secreting subclone) cells were capable of binding IgG. The binding was associated with mucus-producing cells only in the cultures, was enhanced by culture of the cells in galactose-containing medium (which favors mucin production) as compared to glucose-containing medium, and was much greater for the HT29-18N2 cells than for the HT29 cells. LS 174T cells did not bind IgG despite the presence of numerous mucin-containing cells, and Colo 205 and LoVo cell cultures had neither mucin-containing cells nor IgG binding; thus, IgG binding and mucin production are not inseparably linked. By use of monoclonal antibodies to three different molecular-size components of the binding site, we found that a > 200-kDa component probably is necessary but not sufficient for IgG binding, whereas 78-kDa and 110- to 140-kDa components are not necessary.
Binding Sites↗
Characterization of a C alpha gene of swine.
The cDNA sequence encoding the constant region of the porcine IgA heavy chain as well as the exon-intron structure of the germline gene, have been determined. A cDNA clone (1A1) spanning the CH3 domain and part of the CH2 domain was isolated from a porcine mesenteric lymph node cDNA library. Clone 1A1 was aligned with a PCR-generated DNA fragment encompassing the CH1 domain through the 5' end of the CH3 domain to derive the complete cDNA sequence. Comparison with other mammalian C alpha heavy chains (hinge regions excluded) indicated that the deduced amino acid sequence of porcine C alpha is most homologous with the human C alpha subclasses (> 70%), followed by mouse C alpha (61%) and a consensus sequence of the 13 rabbit C alpha heavy chains (59%). The greatest sequence homology was found among the CH3 domains in all species. A striking feature of porcine C alpha is its short six amino acid hinge which like other mammalian IgAs, is encoded with the CH2 domain. Sequence analysis of germline C alpha, generated by PCR from liver or sperm DNA, revealed an exon-intron organization similar to other mammalian C alpha genes. Genomic Southern blot data are consistent with the presence of a single C alpha gene within the porcine genome. Data obtained in these studies will be valuable in pursuing the use of swine as a model in immunological research.
Amino Acid Sequence↗
The immunoglobulins and immunoglobulin genes of swine.
The historical works describing the characterization of swine immunoglobulins are reviewed. The three major isotypes, IgM, IgA and IgG, have been recognized for 25 years and their concentrations in various body fluids, the location of the plasma cells throughout the body which synthesize them and their transport into lacteal secretions and absorption by the gut of the newborn piglet, have been studied by many investigators. Swine like humans, have both kappa and lambda light chains and their frequency of expression is similar to that of humans. Various investigators have provided immunochemical evidence for IgG subclass and allotype diversity, although until the recent advent of molecular biology, the complete sequence of any swine immunoglobulin was unknown. Molecular genetic studies reveal single copies of C alpha and C epsilon but as many as eight copies of C gamma. The sequences of five IgG subclasses, IgG1, IgG2a, IgG2b, IgG3 and IgG4, are now available as well as the sequence and genomic organization of C alpha and the sequence of C mu. Swine CH genes all appear to belong to a single small family very similar to human VHIII. Especially interesting is the high degree of similarity among human and swine Ig genes despite the distinct phylogenetic relationship of these species. The rapid expansion of knowledge and technology in the field of molecular biology, together with the attractiveness of the swine as a model for immunoontogeny, in which the influences of both maternal regulatory factors and intestinal gut flora can be experimentally controlled, promises the beginning of an exciting area in swine immunology.
Animals↗
The sequence organization of the long arm pseudoautosomal region of the human sex chromosomes.
We have analysed the sequence organization of the pseudoautosomal region at the telomeres of the long arms of the human sex chromosomes and shown that it is 320 kb long. A LINE sequence is present on both the X and Y chromosomes immediately adjacent to the breakpoint in homology suggesting that the homology arose as a result of an ectopic recombination event mediated by LINE sequences originally present in non-homologous stretches of X and Y chromosomal DNA. This led to the translocation of sequences from the X chromosome telomere onto the Y chromosome and created a new pseudoautosomal region.
Base Sequence↗
Dissecting the centromere of the human Y chromosome with cloned telomeric DNA.
We have used telomeric DNA to break the human Y chromosome within the centromeric array of alphoid satellite DNA and have created two derivative chromosomes; one consists of the short arm and 140 kb of alphoid DNA, the other consists of the long arm and 480 kb of alphoid DNA. Both segregate accurately at mitosis. It is known that there is no large scale sequence duplication around the alphoid DNA and so the simplest interpretation of our results is that the sequence responsible for accurate segregation is the alphoid DNA itself. Although the long arm acrocentric derivative segregates accurately it lags with respect to the other chromosomes in about 10% of anaphase cells and thus additional sequences may be required for orderly segregation. The short arm acrocentric chromosome is probably no larger than 12 Mb in size and thus our results also demonstrate that chromosomes of this size are capable of accurate segregation.
Cells, Cultured↗
Ultraviolet B light-induced suppression of contact sensitivity is not abolished by cyclophosphamide.
Dose responses for ultraviolet B light (UVB)-induced suppression of contact sensitivity were studied in mice, with and without cyclophosphamide (Cy) pretreatment, to investigate the role of Cy-sensitive suppression. Mice were irradiated on the back, sensitized on the abdomen, and challenged on the ears. Half of the mice were injected intraperitoneally with 200 mg/kg of Cy 3 days before being sensitized. Ultraviolet B light radiation reduced the ear swelling reactions in a linear relation to the log10 of the dose. Fifty percent suppression was shown by the computer-generated regression line at approximately 4.8 kJ/m2 of UVB radiation, with complete suppression at approximately 65 kJ/m2. In mice pretreated with Cy, ear swelling was increased, showing inhibition of a Cy-sensitive suppressive component of the contact sensitivity reaction. This Cy-sensitive component also was seen in mice treated with UVB, but with higher doses of UVB, there still was a UVB-dose-dependent decline in ear swelling in Cy pretreated mice, and there was complete suppression of reactions with the highest doses of UVB in the Cy-treated mice. Therefore, there is a second mechanism, not sensitive to Cy, that causes UVB-induced immune suppression.
Analysis of Variance↗
Lymphocyte function-associated antigen-1 is required for maximum elicitation of allergic contact dermatitis.
Cell adhesion molecules (CAMs) are known to play an important role in cell-mediated immunity and inflammation. To investigate the importance of one of the CAMs, lymphocyte function-associated antigen-1 (LFA-1) in allergic contact dermatitis (ACD), a specific anti-LFA-1 monoclonal antibody was injected into the ears of mice after sensitization but prior to challenge with dinitrofluorobenzene (DNFB). BALB/c mice were sensitized on the dorsal skin with DNFB, and challenged on the ears 6 days later. The effect of the antibody on the elicitation phase of contact sensitization was determined by its intradermal injection into the pinnae of the mice at doses of 1-40 micrograms. At 24 and 48 h after challenge, ear swelling was dose-dependently suppressed by injection of LFA-1 antibody at doses of 2-40 micrograms, which are less than 10% of the systemic dose required for effective suppression of delayed-type hypersensitivity in previous studies. Maximal inhibition of ear swelling (44%) was observed after injection of 20 micrograms of anti-LFA-1 antibody. Inhibition of ear swelling was accompanied by a reduction in dermal oedema and leucocyte infiltration into the dermis. Our results suggest that LFA-1 plays a significant role in the elicitation of ACD reactions, and also that our test system is a sensitive and useful means of evaluating the blocking effect of antibody to adhesion molecules thought to be involved in the elicitation phase of ACD.
Animals↗
Correlation between serological and mucosal inflammatory responses to Helicobacter pylori.
In 82 patients who underwent gastroduodenoscopy, acute and chronic gastric mucosal inflammation was scored for severity, and systemic humoral immune responses to Helicobacter pylori antigens were assessed by enzyme-linked immunosorbent assays. On the basis of culture, gastric histology, and serologic evaluation, 33 patients were classified as H. pylori infected and 36 were classified as uninfected. Thirteen patients had negative cultures and stains but were seropositive and were analyzed separately from the other two groups. Specific serum immunoglobulin G (IgG) subclass responses to H. pylori whole-cell antigens and specific IgG responses to the 54-kDa heat shock protein homolog (Hp54K) and vacuolating cytotoxin were significantly greater in infected than in uninfected patients as were specific IgA responses to whole-cell antigens and cytotoxin (P < 0.001). Among the H. pylori-infected persons, serum IgG responses to Hp54K and to the vacuolating cytotoxin were correlated with acute mucosal inflammatory scores. In contrast, serum IgA responses to whole-cell sonicate and to vacuolating cytotoxin were inversely related to chronic inflammatory scores. By multivariant regression analysis, only specific serum IgG responses to Hp54K correlated with severity of inflammation (both acute and chronic; P < 0.001); these responses may be markers of inflammation or these antibodies could play a direct role in the pathogenesis of H. pylori-induced inflammation.
Antibodies, Bacterial↗
Enzyme linked immunosorbent assay (ELISA) and immunoprecipitation studies on anti-goblet cell antibody using a mucin producing cell line in patients with inflammatory bowel disease.
Circulating anti-goblet cell antibody and its corresponding antigen in patients with inflammatory bowel disease were investigated. Anti-goblet cell antibody in the serum was examined by immunocytochemistry and enzyme linked immunosorbent assay (ELISA), using a colonic cancer cell line, HT29-18-N2, which differentiates into intestinal goblet cells. The frequencies of anti-goblet cell antibody detected by immunocytochemistry were 14 in 48 patients with ulcerative colitis (29%) and five in 15 patients with Crohn's disease (33%). By ELISA, the frequencies of anti-goblet cell antibody were 38% in ulcerative colitis and 33% in Crohn's disease. This antibody did not relate directly to anti-neutrophil cytoplasmic antibodies (ANCA), although the serum samples positive for anti-goblet cell antibody were commonly positive for ANCA in ulcerative colitis. Immunoprecipitation and SDS polyacrylamide gel electrophoresis (PAGE) study showed that the antibody in the ELISA positive serum samples recognised a > 200 kD goblet cell antigen, which remained unchanged after reduction, indicating that it consists of single chain polypeptides. These results suggest that there is a subgroup of inflammatory bowel disease that has circulating anti-goblet cell antibody reactive with a > 200 kD antigen. The antibody detected by newly established ELISA will be a disease marker for this group and the identification of the corresponding antigens may be important for the understanding of the underlying immune abnormalities.
Adolescent↗
Surrogate tissues for detecting brain microemboli after cardiopulmonary bypass.
During cardiopulmonary bypass (CPB) microemboli lodge in the brain and other organs. Microemboli were counted in tissue samples of skin, muscle and brain from autopsy cases that had recently undergone CPB, and in skin and muscle biopsies obtained from patients before and after CPB. Unlike the brain, skin and muscle showed few microemboli.
Biopsy↗
Alkaline phosphatase histochemical staining in the study of germinal matrix hemorrhage and brain vascular morphology in a very-low-birth-weight neonate.
We evaluated the utility of alkaline phosphatase (AP) histochemical staining for studying intraparenchymal vascular morphology in the brain of a 31-wk-gestation (1480 g) neonate who died of respiratory insufficiency after 23 h. In this baby, afferent cerebral vessels (arteries, arterioles, and capillaries) stained with AP, whereas efferent vessels (venules, veins) did not. The large periventricular channels in the germinal matrix were determined to be veins, according to AP staining criteria. Arterioles connected with these large periventricular veins after passing through 4- to 6-microns capillaries. Branchings and connections of the cerebral circulation were conventional; i.e. no arterial rete or arteriovenous shunts were found. With this method of differential vascular staining, bleeding in the germinal matrix was found to be perivenous only. No dilated capillaries or arterioles were seen. Smooth muscle was identified in extrastriatal medullary arteries. This preliminary investigation suggests that AP histochemical staining is an excellent method for studying brain vascular morphology and pathology of the very-low-birthweight neonate.
Adult↗
Effect of ultraviolet-inducible cytokines on melanoma growth in vivo: stimulation of melanoma growth by interleukin-1 and -6.
Ultraviolet light of wavelengths 280-320 nm (UVB) can induce transcription of cytokine mRNAs and increase expression of the corresponding proteins in the epidermis. In particular, UVB can stimulate keratinocyte synthesis of interleukin-1 (IL-1), IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta). Several of these cytokines can influence the growth of tumour cells as well as the host response to these tumours. In this study we examined the effect of IL-1, IL-6, IL-8, TNF-alpha and TGF-beta on the growth of melanoma in vivo and in vitro, using the murine B16 melanoma and its syngeneic host, the C57BL/6 mouse. Mice were injected with 0.1-1.5 micrograms of recombinant cytokine subcutaneously every other day following a subcutaneous injection of 1 x 10(5) B16 cells (F-10 clone). In this model, tumours appeared within 12-14 days, and IL-1 and IL-6 stimulated tumour growth in vivo. TNF-alpha, TGF-beta, IL-2 and IL-8 had no significant effect. In contrast to the in vivo effects, TNF-alpha inhibited B16 cell growth in vitro and IL-6 stimulated B16 cell growth. The in vivo IL-1 effect on tumour growth in mice was examined in greater detail. IL-1-treated animals showed tumours approximately 5-fold greater in size than those of the control animals. The IL-1-treated animals also showed highly vascularized tumours that invaded underlying muscle tissue more rapidly than controls. These tumors also showed a strong positive reaction with antibody to intercellular adhesion molecule-1.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Telomere directed fragmentation of mammalian chromosomes.
Cloned human telomeric DNA can integrate into mammalian chromosomes and seed the formation of new telomeres. This process occurs efficiently in three established human cell lines and in a mouse embryonic stem cell line. The newly seeded telomeres appear to be healed by telomerase. The seeding of new telomeres by cloned telomeric DNA is either undetectable or very inefficient in non-tumourigenic mouse or human somatic cell lines. The cytogenetic consequences of the seeding of new telomeres include large chromosome truncations but most of the telomere seeding events occur close to the pre-existing ends of natural chromosomes.
Animals↗