The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology

The terminology for human papillomavirus (HPV)-associated squamous lesions of the lower anogenital tract has a long history marked by disparate diagnostic terms derived from multiple specialties. It often does not reflect current knowledge of HPV biology and pathogenesis. A consensus process was convened to recommend terminology unified across lower anogenital sites. The goal was to create a histopathologic nomenclature system that reflects current knowledge of HPV biology, optimally uses available biomarkers, and facilitates clear communication across different medical specialties. The Lower Anogenital Squamous Terminology (LAST) Project was cosponsored by the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology and included 5 working groups; 3 work groups performed comprehensive literature reviews and developed draft recommendations. Another work group provided the historical background and the fifth will continue to foster implementation of the LAST recommendations. After an open comment period, the draft recommendations were presented at a consensus conference attended by LAST work group members, advisors, and representatives from 35 stakeholder organizations including professional societies and government agencies. Recommendations were finalized and voted on at the consensus meeting. The final, approved recommendations standardize biologically relevant histopathologic terminology for HPV-associated squamous intraepithelial lesions and superficially invasive squamous carcinomas across all lower anogenital tract sites and detail the appropriate use of specific biomarkers to clarify histologic interpretations and enhance diagnostic accuracy. A plan for disseminating and monitoring recommendation implementation in the practicing community was also developed. The implemented recommendations will facilitate communication between pathologists and their clinical colleagues and improve accuracy of histologic diagnosis with the ultimate goal of providing optimal patient care.     

In vivo behavior of human radioiodinated antithrombin III: distribution among three physiologic pools

It has recently been shown that antithrombin III (AT) distributes between plasma, a noncirculating vascular-associated pool and an extravascular pool in rabbit. Study of the in vivo behavior of autologous human 131I-AT demonstrates that in humans AT also distributes among three pools that are analogous to those found in rabbit. From the in vivo kinetic behavior of the 131I-labeled AT, the fractions of total-body AT in the plasma, noncirculating vascular- associated, and extravascular pools were calculated to be 0.393 +/- 0.015, 0.109 +/- 0.016, and 0.496 +/- 0.014, respectively. From three- exponential plasma radioactivity disappearance curves, an average plasma fractional catabolic rate, j3, of 0.576 +/- 0.034 day-1 was obtained for five healthy young men. This is almost identical to the result obtained if plasma 131I-AT disappearance is assumed to fit a two- exponential curve (0.546 +/- 0.038), where the constant C2 from *Ap(t) = C1e-a1t + C2e-a2t is assumed to be equal to 1 - C1. The fraction of the total vascular AT catabolized daily, j3.5, was calculated to be 0.457 +/- 0.034, and the fractional catabolic rate of total-body AT, jT, averaged 0.2271 +/- 0.0176. The results give further support to a model of in vivo behavior in which the vascular AT distributes between plasma and an endothelial receptor. Thus, the latter may serve to mediate activation of AT for its reaction with coagulation proteases and to mediate its entrance into the endothelial cell, where it is either transported to the extravascular fluids or is catabolized.     

The 18- to 23-kb deletion of the Macedonian delta beta-thalassemia includes the entire delta and beta globin genes

Restriction endonuclease mapping analyses were made of DNA from a few members of a Macedonian family with hematological characteristics of delta beta-thalassemia, ie, microcytosis, normal HbA2 levels, and elevated levels of HbF (7% to 14%) with G gamma (average 40.5%) and A gamma T chains (average 59.5%). A large deletion of 18 to 23 kb was present with a 5' breakpoint within a 670-bp segment of DNA between the HpaI and NcoI restriction sites 5' to the delta globin gene, and a 3' breakpoint between the BamHI and HpaI restriction sites located some 9 to 13 kb 3' to the beta globin gene. This deletion is different from those present in other types of G gamma A gamma(delta beta)zero- thalassemia. The similarity of the hematological expression of these delta beta-thalassemic conditions which have somewhat comparable 5' breakpoints supports the idea that an important fetal hemoglobin- controlling region lies between the psi beta and delta globin genes.     

Effect of recombinant granulocyte colony-stimulating factor on neutrophil kinetics in normal young and elderly humans

Recombinant granulocyte colony-stimulating factor (G-CSF) was administered to healthy young (n = 32) and elderly (n = 19) volunteers (0 microgram/d, 30 microgram/d, or 300 microgram/d) to determine its effect on neutrophil production, blood kinetics, and tissue migration. Measurements included blood counts (daily), marrow neutrophil pool sizes and neutrophil tissue migration (baseline and day 5), blood kinetics (day 6), and marrow transit time while on drug (days 6 to 14). G-CSF markedly expanded the marrow neutrophil mitotic pool and shortened the transit time of the postmitotic pool (control, mean = 6.4 days; 300 microgram/d, mean = 2.9 d). G-CSF increased neutrophil production without significantly altering blood neutrophil half-life or margination. Compared to control, neutrophil accumulation in skin chambers decreased by about 50% in the 300 microgram/d group in both young and elderly subjects. G-CSF induced neutrophilia by stimulating proliferation of marrow neutrophil precursors and accelerating neutrophil entry into the blood. Decreased neutrophil inflammatory responses measured with the skin chamber technique may be because of the relative immaturity of the circulating cells or to alterations in neutrophil phenotype induced by G-CSF.     

The effect of inhaled budesonide on the diurnal variation in airway mechanics, airway responsiveness and serum neutrophil chemotactic activity in Asian patients with predominant nocturnal asthma

The effectiveness of inhaled corticosteroids in the control of daytime symptoms in asthma is well established, but the specific use against nocturnal asthma has not been systematically studied in Asian patients. This study examined the effect of treatment with inhaled budesonide on the nocturnal variation in measurements of airway calibre, bronchial hyperresponsiveness to inhaled histamine and circulating neutrophil chemotactic activity in Asian patients with nocturnal asthma. Thirty patients, with nocturnal asthma, were randomized into a 2-month, double-blind, parallel group study. Twice as many subjects were allocated to the group who received two consecutive months of inhaled budesonide 1600 μg daily as to the group who received placebo followed by budesonide. Spirometry, lung mechanics, bronchial hyperresponsiveness and serum neutrophil chemotactic factor (NCA) were measured at 16.00 h, 22.00 h and at 04.00 h on 3 days and nights, 4 weeks apart before and after either placebo or budesonide. The combined measurements for the two groups at 04.00 h before and after treatment with budesonide were: forced expiratory volume in 1 s (FEV₁) mean (SEM) litres 1.34 (0.17) before, 2.00 (0.19) after; thoracic gas volume (TGV) litres 3.05 (0.32) before, 2.25 (0.14) after; specific airway conductance (sGaw) (cmH20.0 sec)^?1 0.39 (0.07) before, 1.16 (0.17) after; PD₂₀μg geometric mean 1.16 before, 44.74 after; neutrophil chemotactic activity (NCA) in units of graduations of migration 98.8 (4.2) before, 101 (14.2) after. The data showed that short and intermediate term high dose inhaled budesonide is an effective specific treatment for nocturnal asthma in Asian patients, resulting in marked improvements in symptoms and in lung mechanics, and reductions in the diurnal variations in bronchial hyperresponsiveness, before any change could be demonstrated in a circulating marker of airway inflammation.     

Correlation of the biologic effects and binding of cytochalasins to human polymorphonuclear leukocytes

Treatment of human PMNs with cytochalasins (CE, CD, CB, and H2CB) results in alteration of cell morphology and inhibition of cell motility. Morphological changes are similar to those reported for nonamoeboid fibroblasts--rounding, zeiosis, and arborization. Mean cell velocity of PMNs, as measured by quantitative analysis of time-lapse videotape recordings, was reduced to 0.1 micron/min (control, 7.3 +/- 4.2 micron/min). Phagocytosis by PMNs, as measured by phagocytosis of latex beads, was inhibited by 75%. The relative potency of the cytochalasins for inducing morphological change or for inhibiting locomotion and phagocytosis is similar to their relative potencies for affecting non-amoeboid cells: CE greater than CD greater than CB greater than or equal to H2CB. Quantitative binding of 3H-CB to purified PMNs under equilibrium conditions reveal two types of specific CB binding sites: high-affinity sites (KD approximately 3 x 10(-7) M, 3 x 10(6) sites/cell) and low affinity sites (KD approximately 2 x 10(-6) M). The relative affinities of the cytochalasins for the high-affinity and low-affinity CB binding sites parallel their relative potencies for inducing biologic effects (i.e. CE greater than CD greater than CB greater than or equal to H2CB).     

Infection of human T-cell leukemia virus type I and development of human T-cell leukemia lymphoma in patients with hematologic neoplasms: a possible linkage to blood transfusion

Among 354 adult patients with either hematological malignancy or aplastic anemia, eight were positive for anti-HTLV-I antibodies; six of eight had received multiple transfusions. There was an approximately 3.5-fold increase (P less than .001) of HTLV-I seropositivity in the patients with hematologic disease (8 of 354, 2.23%) compared to the healthy adults older than 20 years (34 of 5252, .65%). Two hematological patients, one with Hodgkin's disease and one with acute promyelocytic leukemia, were found to be positive for HTLV-I, and developed and died of adult T-cell leukemia/lymphoma (ATL) subsequently. Both were long-term survivors of the primary disease and had received multiple transfusions. The latent period from blood transfusion to onset of ATL was 6 months and 11 years, respectively. Immunocompromised patients, who were seropositive for HTLV-I, may be at increased risk for ATL compared to healthy carriers of HTLV-I, and the latent period may be shorter.     

Activated immunocompetent cells in human skin lymph derived from irritant contact dermatitis: an immunomorphological study

By means of microsurgical lymph cannulation, skin lymph was sampled in the course of a sodium lauryl sulphate (SLS)-induced irritant contact dermatitis in human volunteers. The lymph cells were isolated by centrifugation, and then characterized immunocytochemically using different monoclonal antibodies, and in the late phase of the skin reaction also by electron microscopy. Analyses of lymph cells before the induction of the contact dermatitis revealed median values of about 60% T cells (CD4/CD8 ratio about 2:1), 4% Langerhans cells (LCs), and 1% B cells. The remainder were varying proportions of erythrocytes and uncharacterized cells. During the skin reaction, and even after resolution of the clinical signs of dermatitis, a relative and absolute increase of T and B cells, as well as of HLA-DR positive cells, paralleled the previously reported increase of LCs; a high percentage of the T cells were CD4 and CD8 negative. In addition, surface markers such as CD11a, CD25, CD54 and CD58 were detected on lymph cells sampled during the irritant skin reaction. Cell rosettes observed in the lymph throughout the experiment were analysed in the late phase of the skin reaction, and showed a central LC with three to five peripheral, in part activated, T cells, ultrastructurally revealing gap junction-like structures between the two cell types. These data indicate that immunocompetent cells in the skin are activated by a variety of non-immunological stimuli such as operative trauma and irritant contact dermatitis.     

Vulnerability and protective factors for posttraumatic stress disorder

A review is given of pre-, peri- and post-traumatic factors that increase or decrease the risk of developing posttraumatic stress disorder (PTSD). With the exception of extremely severe stressors, vulnerability and protective factors explain much of the probability of developing PTSD. The etiology of PTSD is multifactorial, and variables related to the individual, their life situation at the time of exposure, the stressor, and the recovery environment tend to interact.     

Fibril Amyloid Enhancing Factor (FAEF)-Accelerated Amyloidosis in the Hamster is Not Dependent on Serine Esterase Activity and Mononuclear Phagocytosis

Cells of the mononuclear phagocytic system (MPS) were described as playing a decisive role in amyloidogenesis. A relationship between the amyloid enhancing factor (AEF) and MPS cells was suggested and recently AEF activity was attributed to a serine esterase (SE) of leucocytic origin. In the present study, no correlation was found between the SE content and AEF activity in either peritoneal cell lysates or AEF preparations of different origin. Furthermore, pretreatment of fibril AEF (FAEF) with the SE inhibitor phenylmethylsulphonyl fluoride (PMSF) did not affect its activity in the hamster. Blockade of the MPS by dextran sulphate did not inhibit deposition of amyloid after intravenous injection of FAEF but amyloid deposition was inhibited when FAEF was administered intraperitoneally. These results suggest that MPS cells could be involved in transport of AEF, but that phagocytic activity of MPS cells is not essential in AA-amyloid fibrillogenesis. It is concluded that these results are not consistent with the previously suggested nature of the AEF or with the proposed central role of the MPS in amyloidogenesis.