A practical approach to interpretation of corneal specimens

Corneal specimens form only a small part of the routine practice for most histopathologists but their assessment often requires considerable effort and specialized knowledge. The most common corneal specimens, full-thickness corneal discs and corneal biopsies, are discussed in this review. Corneal discs removed at keratoplasty are non-urgent specimens, as definitive treatment has already been undertaken, and while the pathologic diagnosis may change the prognosis for the graft, it rarely affects immediate treatment. Accurate diagnosis is still important, and will affect counseling of the patient, but referral to a colleague with a special interest is possible if necessary. Conversely, small partial-thickness corneal biopsies, which are mostly undertaken for culture negative keratitis with underlying suspected infection, are very urgent. Infectious keratitis can follow an extremely aggressive course, resulting in destruction of the cornea within hours. Accurate diagnosis is imperative. Due to the urgency of such specimens and the importance of diagnosis for immediate treatment, referral is not usually possible. It is the role of the pathologist to make optimal use of a small specimen to reach the relevant diagnosis in the minimum space of time.     

Regulation of delayed-type hypersensitivity IV. Antigen-specific suppressor cells for delayed-type hypersensitivity induced by lipopolysaccharide and sheep erythrocytes in mice.

Mice injected subcutaneously with 1 x 10(8) sheep red blood cells (SRBC) developed high levels of delayed-type hypersensitivity (DTH) to SRBC 4-8 days after injection. Such DTH was suppressed when 100 microgram lipopolysaccharide (LPS) was injected intravenously 1-2 days before or at the time of SRBC injection. This suppression of DTH was transferable by spleen, lymph node, thymus and bone marrow cells to sensitized or normal syngeneic recipients, but could not be transferred by serum. Suppressor cells were not induced by LPS alone or SRBC alone, and they were antigen-specific since DTH to chicken red blood cells was not affected. The suppressor cells appeared in the spleen in optimum number 3-4 days after induction. They were theta-negative and Ig-positive as judged by antiserum plus complement treatment and by Ig rosette separation. Attempts to obtain soluble suppressor factor from the suppressor cells by sonication or in vitro incubation were unsuccessful. Mitomycin C treatment of the suppressor cells completely abolished the suppressor activity. Thus, LPS, in conjunction with antigen, appears to induce a population of specific suppressor B cells which are capable of regulating T cell function.     

Large-scale screening of nasal swabs for Bacillus anthracis: descriptive summary and discussion of the National Institutes of Health's experience

In October 2001, a letter containing a large number of anthrax spores was sent through the Brentwood post office in Washington, D.C., to a United States Senate office on Capitol Hill, resulting in contamination in both places. Several thousand people who worked at these sites were screened for spore exposure by collecting nasal swab samples. We describe here a screening protocol which we, as a level A laboratory, used on very short notice to process a large number of specimens (3,936 swabs) in order to report preliminary results as quickly as possible. Six isolates from our screening met preliminary criteria for Bacillus anthracis identification and were referred for definitive testing. Although none of the isolates was later confirmed to be B. anthracis, we studied these isolates further to define their biochemical characteristics and 16S rRNA sequences. Four of the six isolates were identified as Bacillus megaterium, one was identified as Bacillus cereus, and one was an unidentifiable Bacillus sp. Our results suggest that large-scale nasal-swab screening for potential exposure to anthrax spores, particularly if not done immediately postexposure, may not be very effective for detecting B. anthracis but may detect a number of Bacillus spp. that are phenotypically very similar to B. anthracis.     

Association of ulcerative colitis with the inflammatory bowel disease susceptibility locus IBD2 in non-Jewish Caucasians and evidence of genetic heterogeneity among racial and ethnic populations with Crohn disease

Genomewide scanning has been used to identify chromosomal regions encoding susceptibility loci to inflammatory bowel disease (IBD). The greatest evidence for linkage to IBD has been reported for a region of chromosome 12q14 surrounding the microsatellite marker D12S83, with a logarithm of odds score of 5.47 and a positive transmission disequilibrium test, and which was subsequently named IBD2. We wished to confirm this locus by genotyping the highly polymorphic microsatellites D12S1022, D12S1056, and D12S83, spanning a continuous region on chromosome 12 of 342 kb, in a cohort of nonrelated individuals with ulcerative colitis (89 patients), Crohn disease (121 patients), and population-based control subjects (100 patients). In non-Jewish Caucasians, one D12S1022 allele, one D12S1056 genotype, and three D12S83 alleles were found to have statistically significant differences in distribution between the two disease groups and the control population. These data support a significant association of IBD with the IBD2 locus in close vicinity to the three markers studied. The replication of genetic risk loci in a case control association study may indicate susceptibility genes in this region and may facilitate identification of candidate genes for IBD. Subgroup analysis revealed a notable difference in genotype distribution among Jewish Caucasian and African American patients affected with Crohn disease when compared with similarly affected non-Jewish Caucasians. Using Fisher exact test, statistically significant distribution differences were observed for D12S1022 and D12S83. These data indicate that there may be significant genetic heterogeneity between different ethnic and racial IBD populations or may simply reflect differences in marker allele frequencies among populations.     

In vivo inhibition by a monoclonal antibody to CD4+ T cells of humoral and cellular immunity in sheep.

The ability of intravenously injected anti-CD4 and anti-CD8 monoclonal antibody (mAb) to deplete specific lymphocyte subsets in vivo and their effects on antibody responses to ovalbumin (OVA) and Brucella abortus, and skin reactivity to T-cell mitogens was examined in merino lambs. Repeated administration of anti-CD4 or anti-CD8 mAb caused a specific and sustained depletion of target cells from peripheral blood. Anti-CD4 mAb significantly inhibited the in vivo antibody response to OVA but had no effect on the antibody response to LPS of B. abortus. In contrast, antibody responses to both OVA and B. abortus lipopolysaccharides (LPS) remained unaffected in lambs depleted of their CD8+ T lymphocytes. These results confirm the T-cell dependence and independence of antibody responses to OVA and LPS, respectively. Skin reactions elicited by intradermal injections of phytohaemagglutinin (PHA) and concanavalin A (Con A) were also significantly suppressed in lambs depleted of their CD4+ T cells, but treatment with anti-CD8 mAb had no effect on skin responsiveness. Together, these results suggest that mAb can be extremely effective at selectively depleting lymphocyte subsets in vivo and can be used for studying various aspects of immunoregulation and immunity in sheep.     

Childhood adversities as risk factors for alexithymia and other aspects of affect dysregulation in adulthood

BACKGROUND: Affect regulation is assumed to be a biologically based function that can become disrupted by inadequate parenting and by traumatic experiences. We studied the relation between the perceived parental parenting style, and sexual and physical abuse, with alexithymia, dissociation, anxiety and depression. METHODS: In a cross-sectional study psychiatric outpatients were administered a structured interview on childhood physical and sexual abuse and they completed a number of questionnaires about the parenting styles of their parents, and about alexithymia, dissociation and mood pathology. RESULTS: Maternal and paternal parenting styles were moderately correlated with alexithymia and depression. The paternal parenting style was also correlated with dissociation. Optimal parenting of one of the parents had a buffering effect on the degree of alexithymia, but not on the severity of other forms of affect dysregulation. The effect of sexual or physical abuse did not add to that of parental parenting style in terms of predicting affect dysregulation. However, a positively perceived maternal parenting style was found to have a buffering effect in terms of the degree of alexithymia, if sexual abuse had also taken place. CONCLUSIONS: Perceived parenting does appear to be of some significance in the development of alexithymia. Optimal parenting of one of the parents may protect against the development of alexithymia when the parenting of the other parent is perceived as non-optimal. However, it is likely that other factors besides parental care and sexual or physical abuse play an important role in the development of an adequate affect regulation.     

Clinical effectiveness of a mite allergen-impermeable bed-covering system in asthmatic mite-sensitive patients

BACKGROUND: Exposure to allergens plays a role in the development of bronchial hyperresponsiveness and in the chronic inflammatory response seen in asthmatic patients. House dust mites (HDMs) are an important source of allergen. Reduction of these allergens might lead to better lung function and reduction of asthma symptoms. OBJECTIVE: The effect of HDM-impermeable covers on HDM allergen levels, peak flow values, and asthma symptoms were measured. Therefore a randomized clinical trial was carried out. METHODS: Fifty-two allergic asthmatic patients were randomly allocated to use the HDM-impermeable or placebo covers. During the study period, daily peak flow and asthma symptom scores were recorded. Dust samples were taken from the mattresses. RESULTS: We observed a significant reduction in HDM allergen levels on the mattresses after encasing them with HDM-impermeable covers (reduction of 87% of Der p 1 in micrograms per gram of dust; P <.001). Baseline symptoms were so low that no improvement could be established. Morning peak expiratory flow is significantly higher in the intervention group compared with that seen in the placebo group during the study period (beta=20.2; P <.01). CONCLUSIONS: HDM-impermeable covers significantly decreased the level of HDM allergens. Furthermore, morning peak flow was significantly increased during the intervention period. This study indicates that HDM allergen-avoidance measures might have beneficial effects on allergen reduction and asthma outcome.     

Leucocytozoonosis in the Israeli sparrow, Passer domesticus biblicus Hartert 1904

Among the 91 house sparrows (Passer domesticus biblicus Hartert, 1904) examined and caught in the Jordan valley, Israel, 79% were found to be infected with Leucocytozoon fringillinarum Woodcock 1910. In the coastal plain of Israel (South of Tel Aviv), Leucocytozoon infection was found in only 3 out of 43 examined sparrows. In the birds examined, Leucocytozoon gametocytes were present, often in large numbers, in the circulating blood of the visceral organs, whereas they were only sporadic or even absent in the peripheral blood. Gametocytes were seen in the brain capillaries in only a few birds. Only one of the heavily infected sparrows was anemic. Leucocytozoon merozoites were present in the liver and kidneys in only a few infected birds. Merogonic infections did not induce any severe pathological changes, while the gametocyte congestion caused dilation of the blood vessels and sinuses. Tissue damage by the gametocyte parasitemia was most evident in the liver and kidneys. Leucocyte infiltration developed alongside the affected vessels; diffuse necrosis developed in the infiltrated areas. In the kidneys, many tubules were degenerated. Leucocytozoon gametocyte infection in sparrows is unique in that it appears to be confined, for most of its duration, to the visceral circulation, resulting in clinical consequences. Geographically, it is confined to habitats presumably supporting vectors.