Rising incidence of lymphoid malignancies--true or false?

The report contrasts the ascertainment of cases by the regional cancer registry with a specially designed search for records and pathology material which was then submitted to critical review irrespective of the original diagnosis. Boundary changes over the intervening years were accounted for and the results contrasted between time periods and with the cancer registry records. A large proportion of cancer registry cases were never subjected to histopathological diagnosis and comparisons between the new data and records are not easy to undertake. The study describes a probable true rise in the incidence of follicular non-Hodgkin's lymphoma in certain parts of Yorkshire over the last 20 years; there is less evidence of a similar change in Hodgkin's disease incidence over the same period of time.     

A longitudinal evaluation of varying widths of attached gingiva

32 patients with bilateral areas of inadequate attached gingiva on the facial surface of homologous contralateral teeth have been followed for 6 years. Treatment consisted of scaling, root planing, oral hygiene and maintenance at 3- to 6-month intervals or as needed to control inflammation. A free gingival graft was placed on one side (experimental), while the other side served as the unoperated control. Areas of inadequate attached gingiva on control sides, to include those with recession and no attached gingiva, did not demonstrate additional recession or further loss of attachment. Gingival inflammation and plaque were significantly reduced. On experimental sides, the dimension of keratinized and attached gingiva increased and was stable over 6 years. Areas which began with recession and no attached gingiva exhibited a reduction in recession and gain in clinical attachment following the placement of a gingival graft. Examination of patients who had discontinued participation in the study for a period of 5 years revealed a re-establishment of gingival inflammation on the control sides associated with additional recession. Similar changes were not observed in areas treated by a free graft. The findings demonstrate that it is possible to maintain periodontal health and attachment through control of gingival inflammation despite the absence of attached gingiva.     

Anti-CD45 monoclonal antibody YAML568: A promising radioimmunoconjugate for targeted therapy of acute leukemia.

The outcome of hematopoietic cell transplantation for hematologic malignancies may be improved by delivering targeted radiation to hematopoietic organs while relatively sparing nontarget organs. We evaluated the biodistribution of 111In-labeled anti-CD45 antibody in humans using the rat IgG2a monoclonal antibody YAML568 that recognizes a common CD45 epitope present on all human leukocytes. METHODS: Eight patients undergoing bone marrow transplantation received YAML568 labeled with 122 +/- 16 MBq of 111In intravenously followed by serial blood sampling, urine collection, and conjugated view planar gamma-camera imaging up to 144 h after injection. Time-activity curves were obtained using region-of-interest analysis in the accumulating organs and residence times were calculated. An estimate for the radiation-absorbed doses for each organ per unit of administered activity of 90Y was calculated using software for internal dose assessment. The first patient received no unlabeled antibody preloading. The second 2 patients received a preloading dose of 10 mg (0.15 mg/kg). The last 5 patients received a preloading dose of 30-47 mg (0.5 mg/kg). RESULTS: No significant administration-related side effects were seen. The 3 patients receiving no antibody or low antibody preloading had an unfavorable biodistribution with a high initial accumulation of activity in the liver (37%) and the spleen (34%). For the patients receiving 0.5-mg/kg antibody preloading, the estimated radiation-absorbed doses for red bone marrow, spleen, liver, kidney, and total body were 6.4 +/- 1.2, 19 +/- 5, 3.9 +/- 1.4, 1.1 +/- 0.4, and 0.6 +/- 0.1 mGy/MBq, respectively, demonstrating preferential red marrow targeting. A linear regression model showed that the amount of unlabeled antibody preloading per body weight has a strong influence on the estimated red marrow absorbed dose (P = 0.003, R2 = 0.80). CONCLUSION: This study shows that the anti-CD45 monoclonal antibody YAML568 is suitable for delivering selectively radiation to hematopoietic tissues when labeled with 90Y provided that a preloading dose of about 0.5 mg/kg unlabeled antibody is given.     

Degenerative changes in a retina affected with autosomal dominant retinitis pigmentosa

The eyes of a 17-year-old male donor who was affected with autosomal dominant retinitis pigmentosa with variable expressivity have recently become available for study. Initial macroscopic examination of the fundus revealed bone spicules located in 180 degrees of the postequatorial fundus centered on the inferonasal quadrant. Light microscopic examination of the retina showed degeneration within each quadrant characterized by an absence of rods and cones in the equatorial areas, and the presence of photoreceptors in the more peripheral and central retina. Ultrastructural examination disclosed photoreceptors that were abnormal in all regions when compared to a control eye from a 26-year-old donor. Intact rods were restricted to the peripheral quadrants, and intact cones were identified in the fovea and far periphery. In areas of intermediate degeneration, many outer segments were either shortened and disorganized or absent. Regions of severe degeneration were characterized by the complete loss of the photoreceptors and apposition of the external limiting membrane to the retinal pigment epithelium. The density of rods and cones was found to be substantially lower than normal in all regions. In areas of relatively intact photoreceptor outer segments, we found ultrastructural evidence of recent phagocytic activity, and fluorescence microscopy revealed no unusual accumulation of lipofuscin within the pigment epithelium or subepithelial debris. The choroid and inner retina were normal throughout the eye. The normal condition of the choroid, retinal pigment epithelium, and inner retina implies that the primary disorder resides within the photoreceptor cell.     

The CD5+ B cell: a B cell lineage with a central role in autoimmune disease?

It is apparent that B cells are heterogeneous with respect to, for example, the antigens they express on their surface, and the stimuli to which they can respond. It is still unclear to what extent these differences relate to the stage of differentiation (eg. virgin B cells differing from activated B cells or memory cells), or whether distinct developmental lineages might exist. It has been proposed by some authors that, in the mouse, B cells expressing the ly-1 antigen constitute a separate lineage. In man also, a minor population of B cells expresses detectable levels of the CD5 antigen, but far less information is available about these cells. Interest in the CD5+ and ly-1+ B cell subpopulations has been further stimulated by the suggestion that these cells might play a special role in autoimmune disease. Although, in mouse, ly-1+ B cells differ in several respects from ly-1- B cells, the main evidence that they form a separate lineage derives from experiments in which ly-1+ B cells could not be reconstituted with adult bone marrow. It should be borne in mind that the situation is quite different in humans where, following bone marrow transplantation, CD5+ B cells are rapidly restored. Moreover, in the irradiated mice, at least in some of the experiments ly-1+ B cells were in fact reconstituted by adult bone marrow. Furthermore, at least in humans, expression of CD5 can sometimes be induced. There is, as yet, no good evidence that human CD5+ B cells form a distinct lineage, and it is possible that CD5 expression depends upon microenvironmental influences acting on the B cell during its differentiation. Several interesting properties have been attributed to ly-1+ B cells, including the ability to provide help to other B cells, and the secretion of autocrine factors. However there is also evidence that these features are not exclusive to B cells expressing ly-1. It has also been suggested that ly-1+ B cells might be long-lived. It is not yet known whether some of the properties of ly-1+ B cells might be a direct result of their expressing this antigen; this may become more clear when the function of CD5 is elucidated. The suggestion that the repertoire of ly-1+ B cells might be biased towards the expression of certain V genes is very interesting. Many of the hybridomas from neonatal mice produce antibodies which are multi-specific, and therefore well suited to form a first line of defence against potential pathogens.(ABSTRACT TRUNCATED AT 400 WORDS)     

Biosynthesis and secretion of insulin

The mechanisms involved in the biosynthesis, storage and secretion of insulin in the normal pancreatic B-cell have been the subject of intensive investigation during the last twenty years. As a result of this activity a relatively clear picture has emerged about the basic processes involved, and increasing information is available of their regulation and integration. Most of this information is derived from studies with rodent islets, but in general it appears to be applicable to the human B-cell. The article attempts to provide an overview from the vast literature on pancreatic B-cell function; it cannot be entirely comprehensive within the space available.     

Tolerance to ethanol's disruptive effects on operant behavior in rats

The effects of pre-session and post-session daily ethanol injections on the development and loss of tolerance to ethanol's effects on fixed ratio operant performance in rats was assessed using a cumulative dosing procedure. Daily pre-session ethanol administration produced a greater decrease in ethanol sensitivity than did daily post-session ethanol. Both tolerance effects persisted for at least 1 month after the chronic injection phase. No changes in ethanol sensitivity were apparent in the saline control group and no changes in estimated blood ethanol levels were found after the chronic treatments. The post-session ethanol groups displayed a performance decrement during the initial segment of the chronic injection period, but improved significantly across the chronic phase. These data suggest that some delayed effect of ethanol initially impaired performance but that tolerance to this ethanol effect also occurred and probably contributed to the decline in ethanol sensitivity seen in these groups. Compensatory learning as the mechanism for tolerance development in the pre-session and post-session ethanol groups was supported by the finding of no change in ethanol sensitivity in rats exposed to comparable daily ethanol without any concurrent operant task on which the direct, immediate, or indirect, delayed ethanol effects could operate.     

The management of wringer injuries

Summary Between the years 1985–1988, 32 patients with wringer injury of the upper extremity were admitted to our institution. A uniform treatment program was carried out on all patients; this included aseptic wound care, immobilization and elevation of the involved extremity and early coverage of skin defects. The important aspects in the management of wringer injuries are reviewed, and the importance of early coverage of skin defects is emphasized. Furthermore, it was concluded that the surface area of deep ecchymosis measured 48 h after injury was useful as a simple and objective criterion to estimate the extent of final skin necrosis.Presented at 5th Congress of the Asian Pacific Section of the International Confederation for Plastic and Reconstructive Surgery, Istanbul, September 7–10, 1989, Turkey     

Wide range in age of onset for chromosome 1-related familial Alzheimer's disease

Mutations in three different genes on chromosomes 1, 14, and 21 cause autosomal dominant forms of familial Alzheimer's disease (FAD). Most result in an early-onset phenotype. However, several kindreds of Volga German ancestry have the same chromosome 1 gene mutation and demonstrate a relatively older mean age of onset and include individuals with late age of onset. In these families, the mean age of onset is 54.9 ± 8.4 years (range, 40–75 years), mean age at death is 65.9 ± 10.2 years (range, 43–88 years), and mean disease duration is 11.3 ± 4.6 years (range, 5–23 years). This contrasts with a group of 7 families with chromosome 14 mutations in which the mean age of onset is 44.8 ± 4.8 years (range, 30–55 years), mean age at death is 52.6 ± 5.7 years (range, 39–65 years), and mean disease duration is 7.6 ± 3.2 years (range, 2–17 years). (All means are significantly different in the 2 groups of families, p < 0.005.) In the chromo-some 1 families, 7 persons (16%) had an age of onset at or older than 65 years and 22 (54%) survived to age 65 or older versus none in the chromosome 14 families. An example of probable nonpenetrance of disease at age 89 was also found in a chromosome 1 kindred. It is concluded that, unlike the chromosome 14 gene, mutations in the chromosome 1 FAD gene may result in individuals with a late age of onset overlapping with the more common sporadic form of the disease occurring in the general population. In light of the great variability in age of onset in persons with identical mutations, study of the genetic and environmental factors contributing to delayed onset of disease in chromosomal 1 FAD kindreds will be an important area for further investigation. Apolipoprotein E genotype may be one such factor that plays a partial role in this variability.     

An adenomatous polyp case-control study to assess occupational risk factors following a workplace colorectal cancer cluster

To assess potential etiologic factors among a population of Texas polypropylene workers previously found to have an excess of colorectal cancer (concentrated among mechanical and process workers), the authors conducted an adenomatous polyp case-control study. Cases (n = 24) were workers found to have adenomatous polyps during a company-sponsored colorectal cancer screening program, while controls (n = 72) were workers found to be free of polyps. Exposure assessment utilized a thorough industrial hygiene and toxicologic review of operations in conjunction with work activity interviews of cases and controls to develop chemical-specific exposure scores weighted by time, exposure level, and frequency of exposure. Stratified analyses and logistic regression found that cases tended to have higher exposure to pre-extrusion polymer plus additives (odds ratio (OR) = 2.6, 90% confidence interval (CI) 1.1-6.3) and higher exposure to certain finishing additives (OR = 4.8, 90% CI 1.5-15.3). Analyses by job category or area of the plant did not indicate additional risk factors. The exposures identified in this study are discussed in light of the available toxicologic data on these and related compounds. The need for confirmatory experimental and epidemiologic studies is noted.