An experimental assessment of macroscopic enzyme techniques for the autopsy demonstration of myocardial infarction.

Experimental cardiac infarction produced in dogs by coronary artery ligation has been used to investigate the value of macroscopic histochemical enzyme loss in the diagnosis of myocardial infarction at post-mortem. Creative phosphokinase and non-specific dehydrogenase methods gave the best results but became positive only 5-6 hr after infarction. It is concluded that the method is of limited value in autopsy practice.     

The Pathogenesis of Experimentally Induced Trypanosoma brucei Infection in the Dog: II. Changes in the Lymphoid Organs

Marked changes were found in the spleen and lymph nodes of dogs experimentally infected with Trypanosoma brucei. These changes were considered to occur in two phases. First, in animals examined on Days 8 and 16 after inoculation, there was an intense proliferative response; this involved particularly the B-dependent follicular areas and was accompanied by a dramatic increase in the number of plasma cells in the splenic red pulp and medullary cords of the lymph nodes. Although numerous large proliferating lymphoblasts were found in the periarteriolar regions of the spleen and in the peripheral part of the paracortical areas of the lymph nodes, the presence of cells containing Ig in these regions made it difficult to evaluate the degree of involvement of thymus-derived cells. The plasma cell response involved both IgM and IgG, although the increase in IgM-containing cells was most striking. During this initial phase there was focal hemorrhage, deposition of fibrin, necrosis, and infiltration of polymorphonuclear leukocytes in the spleen, these changes being most severe in the peripheral follicular areas. Following the initial proliferative phase and prior to the death of the host during the fourth week of the infection, the spleen and lymph nodes became less reactive, and there was marked disorganization and disruption of their architecture. Compared with characteristics earlier in the infection there was greatly decreased proliferative activity and a reduction in size of the splenic white pulp and lymph node cortices. Germinal centers were reduced in number, size, and activity, had a disorganized appearance, and, by immunofluorescence, showed a reduction of immunoglobulin on the dendritic reticular cells. The lymph node sinuses exhibited a decrease in content of lymphocytes and contained massive numbers of macrophages, including numerous multinucleated giant cells. There was also severe disruption of the reticulum cell network of the sinuses; and accumulations of polymorphonuclear leukocytes, along with extensive deposition of fibrin, were commonly found in the subcapsular sinuses. During this period, foci of erythropoietic cells were present throughout the red pulp of the spleen.     

Diagnostic significance of nerve cells in human CSF with particular reference to CSF cytology in the brain death syndrome

Summary Cytological examination of the cerebrospinal fluid (CSF) in 5 cases of the brain death syndrome treated on a respirator revealed the presence of nerve cells (mostly Purkinje cells), massive pleocytosis with many polymorphonuclear leukocytes, and numerous macrophages containing erythrocytes, leukocytes, lipid droplets, and hemosiderin. Portions of connective tissue with well preserved capillaries, and debris which could not be more closely identified, were also found.Neuropathological examination in 4 cases revealed progressive autolysis of brain tissue and displacement of the autolyzed tissue into the subarachnoid space of the spinal canal, partly due to tonsillar herniation. All five patients exhibited clinical signs of brain death and had been placed on respirators for various periods of time.The cytological findings in the CSF, together with the clinical signs of brain death, constitute an intravital morphological indication of brain tissue autolysis.This paper was presented in part at the 11th Danube Symposium for Neurological Sciences in Budapest 1978     

Developmental origins of midlife physical performance: evidence from a British birth cohort

The authors hypothesized that 1) physical growth, as a marker of the early development of muscle fibers, and 2) advanced childhood motor and cognitive abilities, as markers of central nervous system development, would be positively related to midlife standing balance and chair rising, independently of later life experiences. They tested these hypotheses in a representative British sample of 1,374 men and 1,410 women aged 53 years in 1999 with prospective childhood measures of heights and weights, age at first standing and walking, cognitive ability, and motor coordination. Weight gain before age 7 years was positively related to adult performance in men but not women, independently of later body size, social class, physical activity, and health status. Attainment of motor milestones at the modal age and higher scores on tests of cognitive ability and motor coordination were associated with better performance, independently of other factors. This study is the first to show that childhood growth and development affect midlife performance; prevention of disability and frailty in later life may need to start early.     

The effect of brevenal on brevetoxin-induced DNA damage in human lymphocytes

Brevenal is a nontoxic short-chain trans-syn polyether that competes with brevetoxin (PbTx) for the active site on voltage-sensitive sodium channels. The PbTxs are highly potent polyether toxins produced during blooms of several species of marine dinoflagellates, most notably Karenia brevis. Blooms of K. brevis have been associated with massive fish kills, marine mammal poisoning, and are potentially responsible for adverse human health effects such as respiratory irritation and airway constriction in beach-goers. Additionally, the consumption of shellfish contaminated with PbTxs results in neurotoxic shellfish poisoning (NSP). The purpose of the present study was to determine whether PbTx could induce DNA damage in a human cell type, the lymphocyte, and if so, whether the damage could be antagonized or ameliorated by brevenal, a brevetoxin antagonist. The DNA damage may occur through both endogenous and exogenous physiological and pathophysiological processes. Unrepaired or erroneously repaired DNA damage may result in gene mutation, chromosome aberration, and modulation of gene regulation, which have been associated with immunotoxicity and carcinogenesis. A single-cell gel electrophoresis assay, or comet assay, was used to determine and compare DNA damage following various treatments. The data were expressed as tail moments, which is the percentage of DNA in the tail multiplied by the length between the center of the head and center of the tail (in arbitrary units). The negative control tail moment was 29.2 (SE=±0.9), whereas the positive control (hydrogen peroxide) was 72.1 (1.5) and solvent (ethanol) was 24.2 (2.1). The PbTx-2 (from Sigma, St. Louis, MO, USA), 10^–8 M was 41.3 (3.6), PbTx-9 (Sigma), 10^–8 M was 57.0 (5.3), PbTx-2 (from University of North Carolina at Wilmington, UNCW), 10^–8 M was 49.4 (9.9), and PbTx-3 (UNCW), 10^–8 M was 64.0 (6.4). 1.0 g/ml brevenal applied 1 h before the PbTxs protected the lymphocytes from DNA damage; PbTx-2 (Sigma), 31.3 (2.1); PbTx-9 (Sigma), 35.5 (2.9); PbTx-2 (UNCW), 33.9 (1.4); PbTx-3 (UNCW), 34.9 (1.25). The tail moment for 1.0 g/ml brevenal alone was 30.8 (2.6). The results indicate that extensive genotoxic damage is induced by PbTx-2 and 9 (Sigma), and PbTx-2 and 3 (UNCW) in normal human lymphocytes, which is fully antagonized by brevenal. This suggests that the immune systems of individuals exposed to PbTx during harmful algal bloom (HAB) events may be at risk.