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Biomedical subjects

D J Innes

Publications and source records attributed to D J Innes.

At least 19 recordsLinked to original sources

Outcomes of reciprocal invasions between genetically diverse and genetically uniform populations of Daphnia obtusa (Kurz).

Ecological theory predicts that genetic variation produced by sexual reproduction results in niche diversification and provides a competitive advantage both to facilitate invasion into genetically uniform asexual populations and to withstand invasion by asexual competitors. We tested the hypothesis that a large group of diverse clones of Daphnia obtusa has greater competitive advantage when invading into genetically uniform populations of this species than a smaller group with inherently less genetic diversity. We compared competitive outcomes to those of genetically uniform groups of small and large size invading into genetically diverse populations. Genetically diverse invaders of initially large group size increased their representation by more than those of initially small size; in contrast, genetically uniform invaders of initially large group size diminished on average by more than those of initially small size. These results demonstrate an advantage to the genetic variation produced by sexual reproduction, both in invasion and resisting invasion, which we attribute to competitive release experienced by individuals in genetically diverse populations.

Animals↗

Association studies of neurotransmitter gene polymorphisms in alcoholic Caucasians.

Ethanol enhances mesolimbic/cortical dopamine activity in reward and reinforcement circuits. We investigated the hypothesis that risk for alcoholism may be mediated by genes for neurotransmitters associated with the dopamine reward system as well as genes for enzymes involved in ethanol metabolism. DNA was extracted from brain tissue collected at autopsy from pathologically characterized alcoholics and controls. PCR-based assays showed that alcoholism was associated with polymorphisms of the dopamine D2 receptor (DRD2) TaqI B (P = .029) and the GABAA-beta2 subunit C1412T (P = .012) genes, but not with the glutamate receptor subunit gene NMDAR2B (366C/G), the serotonin transporter gene (5HTTL-PR), the dopamine transporter gene DAT1(SLC6A3), the dopamine D2 receptor gene DRD2 TaqI A, or the GABAA alpha1(A15G), alpha6(T1519C), and gamma2(G3145A) subunit genes. The glial glutamate transporter gene EAAT2 polymorphism G603A was associated with alcoholic cirrhosis (P = .048). The genotype for the most active alcohol dehydrogenase enzyme ADH1C was associated with a lower risk of alcoholism (P = .026) and was less prevalent in alcoholics with DRD2TaqIA2/A2 (P = .047), GABAA-beta2 1412C/C (P = .01), or EAAT2 603G/A (P = .022) genotypes. Combined DRD2TaqI A or B with GABAA-beta2 or EAAT2 G603A genotypes may have a concerted influence in the predisposition to alcoholism.

Alcoholism↗

Avoiding the cost of males in obligately asexual Daphnia pulex (Leydig).

Asexual organisms are thought to gain an advantage by avoiding the cost of producing males. In the cladoceran Daphnia pulex (Leydig), male production is determined by the environment and is independent of the origin of the asexual obligate parthenogens from the sexual cyclical parthenogens. If there is a cost to producing males, successful obligate parthenogens should have reduced or eliminated male production. Field and laboratory observations showed that obligate parthenogens have much-reduced male production compared to cyclical parthenogens. Although the reduction or elimination of males in the obligate parthenogens suggests that the cost of males is avoided, the coexistence of sexual and asexual forms of D. pulex may be partially explained by cyclical parthenogens compensating for the cost of males by having greater fecundity. In addition, the absence of a mating constraint for the obligate parthenogens may favour an increased allocation to asexual diapausing eggs earlier in the season compared to the cyclical parthenogens which require mating with males to produce sexual diapausing eggs. No difference in the production of diapausing eggs was observed, probably because males were abundant in populations of cyclical parthenogens and do not appear to limit the production of sexual diapausing eggs. D. pulex is a useful system for determining the ecological consequences of abandoning sexual reproduction and explaining the coexistence of sexual and asexual forms of a species.

Animals↗

Surface expression of intercellular adhesion molecule 1 on epithelial cells in the human adenoid.

Human rhinoviruses enter the host by way of the nose and conjunctiva. Intercellular adhesion molecule 1 (ICAM-1) is the cellular receptor for the majority of rhinoviruses. ICAM-1 expression on the luminal surface of epithelial cells in the upper airway may be an important determinant of virus localization in the airway. Eighteen adenoids and 5 nasopharyngeal biopsies were evaluated by immunohistochemistry for surface expression of ICAM-1. Heavy immunoreactivity of ICAM-1 was found on the surface of a small number of single nonciliated cells in the lymphoepithelium. Squamous epithelial cells showed minimal to no staining, and ciliated epithelium had positive ICAM-1 staining of the basal cells but not on the ciliated border. The localization of ICAM-1 expression to specific, limited areas of the surface epithelium of the nasopharynx may have important implications in the pathogenesis of rhinovirus infections, especially initiation of the host response to rhinovirus.

Adenoids↗

The human adenoid. A morphologic study.

OBJECTIVE: We examined the route by which antigen on the surface of the adenoid may be brought into contact with the lymphoid follicles in the submucosa of the adenoid. DESIGN: We studied under light and electron microscopy 13 adenoids from children undergoing elective surgery. Portions of all of the specimens were fixed in formalin and embedded in paraffin and plastic for hematoxylin-eosin and periodic acid-Schiff staining. Portions of four adenoids were fixed in glutaraldehyde for electron microscopy. RESULTS: Two major types of epithelium were evident by light microscopy: a ciliated or squamous epithelium containing few lymphocytes and a nonciliated-flat epithelium with a heavy infiltration of lymphocytes ("lymphoepithelium"). Scanning microscopy showed the surface of this lymphoepithelium to be composed largely of cells with multiple microfolds known as M-cells. Freeze-fracture technique showed many lymphocytes under the M-cells. Transmission electron microscopy showed the lymphocytes to be located in compartments formed by the epithelial cells. Light microscopy study of 50 serial sections embedded in plastic suggested that the compartments communicated to form intraepithelial channels for the lymphocytes. CONCLUSION: The epithelium of the adenoid has areas with ciliated epithelium adjacent to areas with epithelium containing M-cells and intraepithelial lymphatic channels. HYPOTHESIS: The lymphoepithelium of the adenoid is a mechanism for transporting antigen via the M-cells to the underlying lymphoid follicles.

Adenoids↗

Juxtaglomerular body abnormalities in youth-onset diabetic subjects.

Abnormal microalbuminuria in insulin-dependent diabetic subjects (IDDS) is significantly associated with pre-clinical nephropathy. In youth-onset IDDS declining plasma renin activity is significantly associated with improved albumin excretion, while persistently elevated renin activity is associated with continued abnormal microalbuminuria. To determine if these changes are reflected in changes in cell count in the juxtaglomerular body and if biopsy findings correlate with abnormal microalbuminuria, renal tissue of 20 IDDS (Study IDDS) ages 16 to 31 years, evaluated concurrently for plasma renin activity and microalbuminuria, were examined by light microscopy. Biopsy or autopsy specimens from 21 normal subjects and 32 IDDS (Non-Study IDDS), ages 2 to 25, were also examined. Specimens from the majority of prepubertal and all pubertal and postpubertal Non-Study IDDS and all Study IDDS independently of status of microalbuminuria had morphologic abnormalities. Normal or mesangially expanded glomeruli were found in association with expanded juxta-glomerular bodies and increased cell number, or with sclerotic bodies and decreased cell number. Sclerosis of juxtaglomerular bodies occurred independently of glomerular sclerosis. The highest percentage of glomeruli with expanded juxtaglomerular bodies and high cell count was present in specimens of Study IDDS with the most abnormal levels of microalbuminuria. T lymphocytes, noted within juxtaglomerular bodies, were present in specimens of 62% of the 52 Study and Non-Study IDDS. Abnormalities of the juxtaglomerular body are distinctive features of renal pathology in IDDS. T lymphocytes in the endocrine juxtaglomerular body suggest the presence of an autoimmune process. Confirmatory studies are necessary.

Adolescent↗

Origins of enhancer sequences of recombinant murine leukemia viruses from spontaneous B- and T-cell lymphomas of CWD mice.

Recombinant murine leukemia viruses from the highly leukemic mouse strains AKR, HRS, and C58 usually acquire pathogenic U3 region sequences fro the endogenous xenotropic virus, Bxv-1. However, the majority of tumors from another highly leukemic strain, CWD, contained recombinant viruses that lacked Bxv-1-specific sequences. The nucleotide sequence of the U3 regions of two such CWD recombinants was nearly identical to that of the endogenous ecotropic virus parent Emv-1, but they shared three nucleotide substitutions immediately 3' of the enhancer core. These substitutions were found in recombinant proviruses from about one-third of spontaneous CWD lymphomas as determined by an oligonucleotide hybridization assay of proviral fragments that had been nucleotide substitutions in the CWD viruses were inherited from an endogenous polytropic provirus that is absent in the other highly leukemic strains. On the basis of the results of these and previous studies, we propose that CWD recombinants acquire pathogenic U3 region sequences through recombination with an endogenous polytropic virus or Bxv-1 and that the pathogenicity of these sequences may be related to a sequence motif that is known to bind members of the basic helix-loop-helix class of transcription factors.

Animals↗

Pathogenic determinants in the U3 region of recombinant murine leukemia viruses isolated from CWD and HRS/J mice.

Recombinant murine leukemia viruses (MuLVs) from high-leukemia-incidence mouse strains typically acquire pathogenic U3 region sequences from the genome of the endogenous xenotropic virus, Bxv-1. However, a recombinant virus isolated from a leukemic HRS/J mouse and another from a CWD mouse contained U3 regions that lacked genetic markers of Bxv-1. The U3 regions of both recombinants were derived from the endogenous ecotropic virus Env-1 and had retained a single enhancer element. However, compared with that of Emv-1, the U3 region of each of the recombinant viruses contained five nucleotide substitutions, one of which was shared. To determine the biological significance of these substitutions, chimeric ecotropic viruses that contained the U3 region from one of the two recombinant viruses or from Emv-1 were injected into NIH Swiss mice. All three of the chimeric ecotropic viruses were leukemogenic following a long latency. Despite the presence of an enhancer core motif that is known to contribute to the leukemogenicity of the AKR MuLV SL3-3, the HRS/J virus U3 region induced lymphomas only slightly more rapidly than the allelic Emv-1 sequences. The chimeric virus with the U3 region of the CWD recombinant caused lymphomas more frequently and more rapidly than either of the other two viruses. The results support the hypothesis that one or more of the five nucleotide substitutions in the U3 regions of the recombinants contribute to viral pathogenicity. Comparison of DNA sequences suggests that the pathogenicity of the CWD virus U3 region was related to a sequence motif that is shared with Bxv-1 and is recognized by the basic helix-loop-helix class of transcription factors.

3T3 Cells↗

Cytokeratin in anaplastic large cell lymphoma.

A B-cell anaplastic large cell lymphoma, confirmed by immunohistochemistry and Southern blot immunoglobulin gene rearrangement analysis, contained neoplastic cells that were immunoreactive for cytokeratin using antibodies CAM 5.2, M20, MAK 6, and KS-B17.2. Bands corresponding to cytokeratin 18 and cytokeratins 18 and 8 were seen on Western blot immunoanalysis using antibodies KS-B17.2 and CAM 5.2. The lymph node also contained cytokeratin-positive extrafollicular fibroblastic reticulum cells. Although it is possible that the presence of cytokeratin in the cells of anaplastic large cell lymphoma represented phagocytosed filaments from the reticulum cells, it is more likely that the cytokeratins were synthesized by the malignant cells. The finding of cytokeratin in anaplastic large cell lymphoma, although infrequent, adds to the confusion in the diagnosis of this pleomorphic neoplasm.

Aged↗

UDP-sugar hydrolase isozymes in Salmonella enterica and Escherichia coli: silent alleles of ushA in related strains of group I Salmonella isolates, and of ushB in wild-type and K12 strains of E. coli, indicate recent and early silencing events, respectively.

Escherichia coli contains a single periplasmic UDP-glucose hydrolase (5'-nucleotidase) encoded by ushA. Salmonella enterica, serotype Typhimurium, also contains a single UDP-glucose hydrolase but, in contrast to E. coli, it is membrane-bound and is encoded by the non-homologous ushB gene; Salmonella enterica (Typhimurium) also contains a silent allele of the ushA gene (ushA0). In this report, we show that nearly all natural isolates of Salmonella contain both UDP-sugar hydrolases, i.e. they are UshA+ UshB+. The only exceptions are all from sub-group I (S. gallinarum, S. pullorum, and most Typhimurium strains), are UshA- UshB+, and several have been shown to contain an ushA0 allele. These data, together with the fact that these latter strains are closely related genetically, strongly suggests a recent silencing mutation(s). We also report the presence in E. coli K-12, and in natural isolates of E. coli, of a DNA sequence which is homologous to the ushB gene of Salmonella; since E. coli does not contain UshB activity, we tentatively refer to this sequence as ushB0. Since all E. coli strains investigated are UshB-, we conclude that the silencing mutation(s) occurred relatively early following the divergence of Escherichia coli and Salmonella from a common ancestor that was ushA+ ushB+.

Alleles↗

Case report: increase in CD4 lymphocyte counts after splenectomy in HIV-infected patients.

The records were reviewed of five human immunodeficiency virus (HIV) type 1-infected patients who underwent splenectomy, four for HIV-associated thrombocytopenia and one for gastric compression secondary to splenomegaly. After splenectomy, the four adult patients all had marked, sustained increases in their absolute CD4 lymphocyte counts; greater increases were observed in CD8 lymphocyte counts, accounting for decreases in the CD4:CD8 ratios. In patients 5 (one of triplets, all of whom were infected with HIV after a blood transfusion), absolute CD4 lymphocyte counts were stabilized after splenectomy; the other siblings manifested a decline in CD4 counts, which was associated with a delay in physical development and recurrent episodes of varicella. Immunohistochemical staining of spleen sections demonstrated significantly higher numbers of CD4 cells in splenic tissue from HIV-infected patients than from patients splenectomized secondary to trauma (2,070 +/- 284 vs. 962 +/- 296; p = 0.025). In addition, the HIV-infected patients had significantly higher percentages of CD4 lymphocytes in splenic tissue than in peripheral blood (49.3 +/- 11.0 vs. 20.3 +/- 7.9; p = 0.005), suggesting that CD4 cells were sequestered in the spleens of these patients. These findings have implications for the management of splenectomized HIV-infected patients with regard to optimal timing of initiation of zidovudine therapy and for prophylaxis of Pneumocystis carinii pneumonia.

Acquired Immunodeficiency Syndrome↗

Quantitative criteria for clonality in the diagnosis of B-cell non-Hodgkin's lymphoma by flow cytometry.

Fifty-three cases of B-cell non-Hodgkin's lymphoma (BNHL) and 41 cases of non-BNHL lesions were retrospectively evaluated for the quantitative features of restricted surface light chain expression, pan B-cell antigens, pan T-cell antigens, and T-helper and T-suppressor phenotype using flow cytometry. Decision limit analyses were applied to multiple quantitative indices of immunophenotype to establish criteria for the detection of clonal proliferation associated with BNHL or non-BNHL conditions. Two data expressions (percent population and relative ratios) were simultaneously analyzed. The percent population measures were amenable to parametric analyses; the ratio data were amenable to nonparametric analyses only. Acceptable diagnostic specificity and sensitivity were obtained using decision limits of 75% kappa light chain and 65% lambda light chain for the detection of clonal proliferations associated with BNHL. Comparable diagnostic criteria for light chain ratios of 3:1 and 2:1 were similarly confirmed for cases of kappa clonal and lambda clonal proliferations, respectively. Neither the percent of B-cells present nor the ratio of T-helper cells to T-suppressor cells were of utility in the diagnosis of BNHL. These data confirm the numerical criteria for clonality previously obtained by cell counting studies of immunocytochemical preparations and characterize quantitative criteria for aid in the diagnosis of BNHL based on restricted surface light chain expression as measured by flow cytometry.

Antigens, Differentiation, B-Lymphocyte↗

Primary lymphoma of the temporal bone.

Involvement of the temporal bone by lymphoreticular neoplasm is rare; all reported cases have been of secondary involvement. This article presents what we believe to be the first two reported cases of primary temporal bone lymphoma. The patients, an elderly man and a boy, both presented with infection of the ear, hearing loss, and facial nerve paresis. In both cases, facial paresis resolved after appropriate chemotherapeutic treatment. Patient presentation and clinical course are discussed in light of published work on temporal bone malignancy. Further investigation, including computed tomography and biopsy, should be considered for patients who present with an apparent middle ear infection unresponsive to medical therapy. The development of facial paralysis in such a patient warrants heightened suspicion of malignancy.

Aged↗

The growth of two murine hemangioendotheliomas intracranially, subcutaneously, and in culture, and their comparison with human cerebellar hemangioblastomas: morphological and immunohistochemical studies.

Two thorium dioxide-induced murine hemangioendotheliomas, 42021 TCT and 44347 TST, were grown subcutaneously (for up to 22 and 15 passages respectively) or intracranially (single passage) and were adapted to culture as a monolayer and, in a limited fashion, in an organ culture system or in rotary suspension. They remained viable and malignant following 20-21 years of storage in liquid nitrogen, and had ultrastructural similarities to human hemangioblastomas. The murine tumors were positive for Griffonia (Bandeiraea) simplicifolia isolectin B4 binding, establishing their endothelial nature; however, unlike human hemangioblastic tumors, they did not cross-react with antisera to human factor VIII or fibronectin and they did not demonstrate Ulex europaeus type I lectin (UEA I) binding (as is also the case for non-neoplastic murine vascular endothelial cells). A variety of morphological cell types in cultures derived from the tumors were also positive for Griffonia (Bandeiraea) simplicifolia isolectin B4 binding. Both murine hemangioendotheliomas, when implanted in the cerebrum, were potent inducers of reactive gliosis, but there was no evidence of uptake of glial fibrillary acidic protein. Unlike the human cerebellar hemangioblastomas, murine tumors were malignant and invasive and did not contain stromal cells, nor did they demonstrate Weibel-Palade bodies or extensive pinocytotic activity. Thus, the murine tumors appear to more closely resemble angiosarcomas or epitheloid hemangioblastomas than the cerebellar hemangioblastomas.

Animals↗

The utility of CD20 and CD43 in subclassification of low-grade B-cell lymphoma on paraffin sections.

To identify phenotypic differences among the low-grade lympho-proliferative disorders in paraffin-embedded tissue, we studied 49 cases. All 22 follicular small cleaved cell lymphomas (FSC) were CD43 negative and CD20 positive. In contrast, of 20 small lymphocytic lymphomas (SL), 90% were CD20 positive, 85% were CD43 positive, and 75% were positive for both. Of three lymphomas of intermediate differentiation (IDL), two were CD20 positive and two were CD43 positive. All four monocytoid B-cell lymphomas were positive for CD20 and 50% (two cases) were positive for CD43. Some 86% of 14 chronic lymphocytic leukemias (CLL) (on cytospins) were positive for CD43; all nine of the CLL studied for CD20 were positive and 89% (8/9) expressed both antibodies CD5 expression (on frozen sections or cytospin preparations) was compared to CD43 in 21 cases of SL and CLL. Some 77% were positive for both CD5 and CD20. All seven of the CD5-positive SL also expressed CD43. The antibody MT2 was also examined with the following results: FSC, 16/20 (80%) positive; SL, 18/19 (94%) positive; MBC, 3/3 positive; and ILL, 2/3 positive. All 56 cases tested were CD45RO (UCHL1) negative. We conclude that CD43 is expressed on most cases of low-grade lymphoproliferative disorders with the exception of FSC. Its pattern of expression seems similar to CD5; however, unlike CD5, CD43 can be studied in formalin-fixed tissue. MT2 is not helpful in distinguishing among these lesions.

Antigens, CD↗

Mucin and nonmucin secretagogue activity of Entamoeba histolytica and cholera toxin in rat colon.

Depletion of colonic mucus occurs before invasion of the colonic mucosa by Entamoeba histolytica trophozoites. It is hypothesized that E. histolytica releases a mucus secretagogue; this was studied in a rat colonic loop model. In colonic loops exposed to live amebae, mucus secretion was quantitated by release of acid-precipitable [3H]glucosamine-labeled luminal glycoprotein and by specific immunoassay. Mucus secretion increased in dose-dependent fashion in response to greater than or equal to 1 X 10(5) trophozoites; cholera toxin (20 micrograms per loop), a known mucus secretagogue, elicited a similar response. Thin-section histological analysis of amebae and cholera toxin-exposed loops showed increased mucus release and streaming from mucosal goblet cells with cellular cavitation compared with control loops. Sepharose-4B chromatography of amebae and cholera toxin-stimulated glycoproteins demonstrated secretion of mucins and an 80%-90% increase in low-molecular-weight proteins. E. histolytica trophozoites and cholera toxin enhanced the secretion of preformed and newly synthesized mucin glycoproteins and stimulated colonic glycoprotein synthesis. The level of mucus secretion elicited by axenic E. histolytica strains correlated with their virulence in vivo and in vitro. The amebic secretagogue was released into the culture medium and was heat stable. Mucus secretagogue activity of E. histolytica may contribute to depletion or alteration of the protective mucus blanket, facilitating pathogenesis of invasive amebiasis.

Animals↗

Immunoglobulin gene rearrangement in abnormal lymph node hyperplasia.

The histologic designation "abnormal lymphoid hyperplasia" is applied to lymph nodes demonstrating varying degrees of architectural effacement and/or cytologic atypia. Although some of these cases may be suggestive of non-Hodgkin's lymphoma, a definitive diagnosis is not possible despite careful morphologic and immunophenotypic studies. Because the demonstration of immunoglobulin and T-cell receptor gene rearrangements by Southern blot analysis provides a sensitive marker of lineage and clonality in lymphoid malignant conditions, the frequency with which such gene rearrangements could be identified in abnormal hyperplasia and their significance were studied. DNA samples from lymph node biopsy samples of 11 patients with abnormal lymphoid hyperplasia were analyzed for rearrangements of immunoglobulin and T-cell receptor genes by Southern blot hybridization. Six of these patients had monoclonal B-cell populations identified by immunoglobulin gene rearrangements; all were found subsequently to have non-Hodgkin's lymphoma by repeated biopsy from 8 days to 46 months later. Two patients with negative Southern blot studies also developed lymphoma, one a T-cell non-Hodgkin's lymphoma and one a cutaneous B-cell non-Hodgkin's lymphoma. Three patients without detectable gene rearrangements showed no evidence of malignant lymphoma at 36-, 45-, and 60-month follow-up evaluations. Southern blot analysis thus identified monoclonal B-cell lymphoid populations in a subset of patients with abnormal lymphoid hyperplasia; the presence of clonal immunoglobulin gene rearrangement predicted progression to overt non-Hodgkin's lymphoma.

Aged↗