Correlation of clinical characteristics and small bowel histopathology in celiac disease

The reversible hearing loss in the nonoperated ear noted by patients after ear surgery remains unexplained. This study proposes that this hearing loss is caused by drill noise conducted to the nonoperated ear by vibrations of the intact skull. This noise exposure results in dysfunction of the outer hair cells, which may produce a temporary hearing loss. Estimations of outer hair cell function in the nonoperated ear were made by recording the change in amplitude of the distortion-product otoacoustic emissions before and during ear surgery. Reversible drill-related outer hair cell dysfunction was seen in 2 of 12 cases. The changes in outer hair cell function and their clinical implications are discussed.     

Erythrocyte adenosine triphosphate levels in cattle infected with Babesia argentina

The difference between the PCO2 of alkalinized urine and the PCO2 of blood has been proposed as an indirect means of assessing distal nephron H+ secretion. Following oral bicarbonate loading and alkalinization of the urine to pH greater than or equal to 7.2, eight of nine children with chronic hydronephrosis and four children with idiopathic distal RTA had low (U-B)PCO2 values when compared with seven normal subjects. This findings leads us to conclude that chronic hydronephrosis may cause a form of distal RTA which persists many years after surgical diversion procedures have been carried out.     

Paget's disease and sensori-neural deafness: temporal bone histopathology of Paget's disease

Four cases with Paget's disease of the temporal bone are presented to illustrate the pathogenesis of the associated deafness. One case illustrates the combination of severe deafness due to bilateral otosclerosis with probably asymptomatic bilateral Paget's disease. One case with advanced Paget's disease presents features to explain early stages of sensori-neural deafness before actual cellular invasion of the inner ear. One case of profound deafness due to Paget's disease presents a different stage of cellular invasion of the inner ear by the disease on each side. One case illustrates invasion of the internal auditory meatus by Paget's disease with infiltration of the acoustic division of the nerve and profound deafness.     

Mutations of SURF-1 in Leigh disease associated with cytochrome c oxidase deficiency

Leigh disease associated with cytochrome c oxidase deficiency (LD[COX-]) is one of the most common disorders of the mitochondrial respiratory chain, in infancy and childhood. No mutations in any of the genes encoding the COX-protein subunits have been identified in LD(COX-) patients. Using complementation assays based on the fusion of LD(COX-) cell lines with several rodent/human rho0 hybrids, we demonstrated that the COX phenotype was rescued by the presence of a normal human chromosome 9. Linkage analysis restricted the disease locus to the subtelomeric region of chromosome 9q, within the 7-cM interval between markers D9S1847 and D9S1826. Candidate genes within this region include SURF-1, the yeast homologue (SHY-1) of which encodes a mitochondrial protein necessary for the maintenance of COX activity and respiration. Sequence analysis of SURF-1 revealed mutations in numerous DNA samples from LD(COX-) patients, indicating that this gene is responsible for the major complementation group in this important mitochondrial disorder.     

Association of the mitochondrial 8344 MERRF mutation with maternally inherited spinocerebellar degeneration and Leigh disease

We report previously undescribed or atypical clinical and biochemical manifestations of the mitochondrial DNA MERRF mutation at nucleotide 8344 in members of a multigenerational family with maternally inherited, highly variable neurodegenerative disorder. The more profound neurologic abnormalities include Leigh disease, spinocerebellar degeneration, and atypical Charcot-Marie-Tooth disease.     

Brain regional correspondence between Alzheimer's disease histopathology and biomarkers of protein oxidation

Four biomarkers of neuronal protein oxidation [W/S ratio of MAL-6 spin-labeled synaptosomes, phenylhydrazine-reactive protein carbonyl content, glutamine synthetase (GS) activity, creatine kinase (CK) activity] in three brain regions [cerebellum, inferior parietal lobule (IPL), and hippocampus (HIP)] of Alzheimer's disease (AD)-demented and age-matched control subjects were assessed. These endpoints indicate that AD brain protein may be more oxidized than that of control subjects. The W/S ratios of AD hippocampal and inferior parietal synaptosomes are 30 and 46% lower, respectively, than corresponding values of tissue isolated from control brain; however, the difference between the W/S ratios of AD and control cerebellar synaptosomes is not significant. Protein carbonyl content is increased 42 and 37% in the Alzheimer's HIP and IPL regions, respectively, relative to AD cerebellum, whereas carbonyl content in control HIP and IPL is similar to that of control cerebellum. GS activity decreases an average of 27% in the AD brain; CK activity declines by 80%. The brain regional variation of these oxidation-sensitive biomarkers corresponds to established histopathological features of AD (senile plaque and neurofibrillary tangle densities) and is paralleled by an increase in immunoreactive microglia. These data indicate that senile plaque-dense regions of the AD brain may represent environments of elevated oxidative stress.     

Adenosine triphosphate (ATP) levels in paracetamol-induced cell injury in the rat in vivo and in vitro

We have investigated the relationship between ATP levels and the onset and progression of cell injury induced by paracetamol overdose both in vivo and in vitro. Liver slices obtained from phenobarbitone-induced and non-induced rats were used in a model in vitro system. Slices were exposed to paracetamol (2-10 mM), for 120 min and then incubated without paracetamol for a further 240 min. ATP levels are reduced upon exposure to paracetamol in liver slices from both phenobarbitone-induced and non-induced rats. Cell injury, as quantified by measuring leakage of lactate dehydrogenase (LDH) and potassium (K+), does not become apparent until 240 min, some 120 min after exposure to paracetamol had ended. This irreversible cell injury is not observed in liver slices from non-induced rats. For in vivo studies rats were phenobarbitone-induced and received i.p. injections of 800 mg/kg body weight paracetamol. Hepatic ATP levels were measured and are found to drop sharply by 3 h post-injection. Development of irreversible hepatic cell injury was assessed by measuring serum enzyme (ALT) activity. ALT levels do not rise until 12 h have elapsed. Paracetamol in overdose gives rise to ATP depletion in liver cells, that is early, independent of paracetamol metabolism and probably spread throughout the lobule. In contrast cell injury is found late and only in our phenobarbitone-induced rats. No cell injury is observed in liver slices from non-induced rats. This suggests that while the level of ATP depletion which is observed may be a necessary part of cell injury by paracetamol, it is not a sufficient cause.     

IgE levels in Hodgkin''s disease

Serum IgE levels were determined in a retrospectively selected group of 37 patients with Hodgkin's disease. IgE was determined by a double-antibody radioimmunoassay and expressed as International Units/ml. Patients were analyzed by stage and histologic classification of disease and compared to a group of 102 normal controls. IgE levels for the total group with Hodgkin's disease were significantly higher (p = .02) than controls but there was considerable overlap in ranges. Significant elevation of IgE was found in nodular sclerosing (p = .005) and Stage II Hodgkin's disease p = .0025). IgE elevations seen in other stages and histologic classes were not significant. While not conclusive, the IgE elevations that were found would be consistent with a suppressor T cell dysfunction in Hodgkin's disease.     

Persisting in vitro actin motility at nanomolar adenosine triphosphate levels: comparison of skeletal and cardiac myosins

We have previously demonstrated in vitro actin movement at nanomolar adenosine triphosphate (ATP) levels using heavy meromyosin from skeletal muscle. In the present work we tested whether the motility at nonomolar ATP-concentrations could be supported by cardiac myosin as well. Actomyosin (skeletal actin and bovine ventricular myosin) was pretreated in the in vitro motility assay with 1 mM ATP; subsequently, the ATP level was reduced by multiple rigor-solution washes. By the final rigor-solution wash, the ATP concentration, monitored by the luciferin-luciferase assay, dropped to the order of 100 nM. Even at this low ATP level actin-filament movement remained in evidence. This was in marked contrast to the situation where ATP concentration was gradually increased from zero; in the latter, filament movement began only as ATP levels exceeded 1-2 microM. The difference indicates that potential energy is stored during the initial ATP treatment, and utilized later as the free ATP falls below micromolar levels. Although the velocity of cardiac myosin-supported movement was only one fourth of that of skeletal myosin, both myosins supported actin movement down to similar ATP concentrations. The similarity in response of the two myosins to ATP implies a similar degree of potential energy storage. Given the significantly different specific ATPase activities, however, it appears that the mechanism of potential energy storage and release involves factors different from those involved in the release of chemical energy by the myosin ATPase.     

Relationships between nucleoside triphosphate pyrophosphohydrolase activity and inosine triphosphate accumulation in human erythrocytes

The relationship between nucleoside triphosphate pyrophosphohydrolast (NTPH) (EC 3.6.1.19) activity in erythrocyte lysates and accumulation of radioactive inosine triphosphate (ITP) in human erythrocytes incubated in vitro with [14C]hypoxanthine, was studied in 93 humans. When ITP accumulation, expressed as percentage of total radioactive nucleotides, was plotted against NTPH specific activity, an inverse relationship was found to exist. A continous spectrum of NTPH specific activities and ITP accumulation values exists in the human population and the relationship between these two parameters follows the relationship of substrate concentration to enzyme activity predicted by Michaelis-Menten enzyme kinetics. One interpretation of these data is that the ITP concentration in human red blood cells is controlled by the degradation of ITP to IMP and pyrophosphate catalyzed by NTPH.     

Urine mercury levels in Kawasaki disease

Chronic idiopathic neutrophilia is a rarely recognized finding in otherwise healthy subjects. Described here is a case, not previously reported; in which the patient also had congenital asplenia. Studies carried out to determine the mechanism for the neutrophilia are also described. The results show that the patient's neutrophilia was associated with an enlarged circulating pool of neutrophils, increased production and utilization of neutrophils and a short blood granulocyte survival. The findings differ completely from those observed in patients with chronic idiopathic neutrophilia and intact spleens. The results suggest that (1) the mechanism for neutrophilia in patients with chronic idiopathic neutrophilia varies and depends upon the presence or absence of the spleen, and (2) the spleen has a role in the control of neutrophil production, distribution and utilization.     

Hyperlipidemia and kidney disease: concepts derived from histopathology and cell biology of the glomerulus

The association between hyperlipidemia and renal disease was noted by Virchow as early as the 19th century. Subsequently, similar histopathological lipid depositions were confirmed-in diverse human and experimental renal disease. Although, no studies have been established in man to suggest a causal relationship between lipids and the pathogenesis of renal disease, compelling evidence accumulated in experimental animals suggests a direct role of lipids in the initiation and progression of glomerular disease. These studies showed that cholesterol-feeding to various experimental animals induced the development of glomerular injury. Furthermore, the treatment of hyperlipidemic animals with lipid lowering drugs prevented the development of glomerulosclerosis. In this article, we will review recent advances made in understanding various aspects of lipid-mediated renal injury including biochemical mechanisms of hyperlipidemia, a possible direct role of hyperlipidemia in the pathogenesis of renal disease, pathobiological accumulation of lipids and lipoproteins, biochemical and histological similarities between systemic atherosclerosis and glomerulosclerosis, and cellular processes involved in the development of glomerular disease. Furthermore, we will define cellular and molecular hypotheses that provide putative mechanisms by which hyperlipidemia and atherogenic lipoproteins induce series of cytoregulatory peptide-mediated events involved in the development of glomerular disease.     

Correlation between IL-12 and IL-2 blood levels in the metastatic neoplastic disease: a possible inhibitory feedback system regulating their secretion

Despite the great importance of IL-2 and IL-12 in activating the anticancer immune response in humans, cancer-related physiopathology of their secretion needs to be better investigated. IL-2 blood levels have been proven to decrease in the advanced neoplastic disease, whereas preliminary data would suggest an enhanced secretion of IL-12 in metastatic cancer patients. This study was performed to analyze IL-2 levels in relation to those of IL-12 in metastatic solid neoplasms. The study included 40 untreated metastatic cancer patients. Serum levels of both IL-2 and IL-12 were measured by ELISA. Abnormally low blood levels of IL-2 and elevated values of IL-12 were observed in 16/40 and in 18/40 patients, respectively. Moreover, patients with IL-2 deficiency showed significantly higher mean levels of IL-12 than patients with normal values of IL-2. This preliminary result, by showing an increased secretion of IL-12 in advanced cancer patients with IL-2 endogenous deficiency, would suggest the existance of a possible feedback mechanism operating between macrophage release of IL-12 and T lymphocyte secretion of IL-2.     

Plasma insulin levels in coronary artery disease

Seventy two consecutive patients without a history of diabetes and normal fasting plasma glucose were included in this study of insulin levels. Standard oral glucose tolerance test with 75 gm glucose and fasting and two hour insulin levels were estimated in all patients. Coronary artery disease (CAD) was confirmed or excluded by selective coronary arteriography. In 20 patients, CAD was diagnosed by electrocardiographic (ECG) and clinical evidence of earlier myocardial infarction. Mean fasting plasma insulin was 31.40 +/- 22.2 IU/dl in the CAD positive and 32.3 +/- 13.6 IU/dl in the CAD negative group. The mean two hour plasma insulin was 274.6 +/- 301.1 IU/dl in the CAD positive and 104.8 +/- 74.9 IU/dl in the CAD negative group (p < 0.04). Two hour plasma insulin levels were significantly higher in patients with atherosclerotic coronary artery disease. It is concluded that the estimation of a two hour plasma insulin level after 75 gm of glucose load, could help differentiate CAD from normals.     

Pulmonary histopathology and survival period in morphine-involved deaths

For an evaluation of the survival period in morphine-involved deaths, changes of pulmonary histopathology were investigated in a total of 90 morphine-associated fatalities. Although pulmonary histopathology proved to be heterogeneous, several distinctive histological patterns emerged. While the subgroup with short courses of intoxication ( < 1 h, n = 15) was mostly characterized by slight/moderate alveolar edema (12/15), severe hemorrhages (12/15) and marked acute emphysema (9/15), the phenomena of massive edema (8/15), missing/slight hemorrhages (8/15) and absent/slight emphysema (11/15) dominated in the group with intermediate survival times (1-24 h, n = 15). Intravascular leukocyte accumulations (shock equivalent) occurred in the first group only once, but in the group with the longer survival time in 10 of 15 cases. Delayed deaths ( > 24 h, n = 4) were mainly characterized by purulent bronchitis/pneumonia. Those fatalities (n = 56) that could not be classified by anamnestic data were assessed by histological criteria. In comparison with the evaluation of the survival period by toxicological analyses, concordance was found in 46 cases. Pulmonary histopathology is not a tool for an exact graduation of survival time, but the combination of several key parameters can provide criteria for a differentiation between short ( < 1 h) and longer courses of intoxication.