Frequently subnormal semen profiles of normal volunteers recruited over 17 years

Microcinematographic documentation of mitoses, amitoses, endomitoses, or cytoplasmic fusion shortly after completion of mitoses was done in bone marrow specimens of patients with quantitative platelet disorders and controls. In patients with platelet disorders, most mitoses with cell duplication occurred in large promegakaryocytes after 4-fold nuclear and cytoplasmic enhancement. Normal specimens showed polyploidization happening in small megakaryoblasts, while mitoses with cell duplication were seen only after cultivation in freeze-thawed sera of patients with platelet disorders. Frequently, lymphocytes were observed to contact megakaryoblastic cells undergoing mitoses, amitoses and endomitoses and to enter the cytoplasm of megakaryocytes (emperipolesis), leaving it again after several hours.     

Pulmonary perfusion and density gradients in healthy volunteers

The goal of this study was to measure regional pulmonary perfusion using SPECT and transmission tomography for attenuation correction and density measurements. METHODS: Regional pulmonary perfusion was studied after intravenous injection of radiolabeled particles in 10 supine healthy volunteers using SPECT. Transmission tomography was used to correct for attenuation, measure lung density and delineate the lungs. The effects of attenuation correction on pulmonary perfusion gradients were investigated. RESULTS: In perfusion measurements not corrected for attenuation, we found significant perfusion gradients in the direction of gravity but also significant gradients at isogravitational level. After correction for attenuation, the gravitational gradient was significantly greater than before correction, and gradients at isogravitational level were no longer observed. Perfusion in the ventral lung zone was half of that in the dorsal lung zone. Mean lung density was 0.28 +/- 0.03 g/ml, and density showed a significant increase in the direction of gravity and at isogravitational level. CONCLUSION: We found that SPECT perfusion studies of the lung not corrected for attenuation gave a false impression of nongravitational gradients and underestimate the gradient that is gravity-dependent. Transmission tomography, used for attenuation correction, also quantifies lung density and shows gravity dependent and nondependent density gradients.     

An essential role for free radicals and derived species in signal transduction

OBJECTIVE: To examine whether there is generation of oxygen free radicals (OFR) and lipid peroxidation of cell membrane after volume replacement for burn shock, and to study the relationship between OFR injury and enterogenous endotoxemia. METHODS: Forty-seven burn patients were involved in this study. Among them, 18 had delayed fluid resuscitation (DR) and the others had early fluid resuscitation (ER) within 6 hours postburn. Sixty-six gnotobiotic rats were used in a collaborating experiment as burn models. They were divided into 4 groups: sham injury (n = 6), early resuscitation (n = 24), late resuscitation (n = 24) and vitamins E and C treatment group (n = 12). All the rats, except those in the sham injury group, were inflicted with 40% total body surface area (TBSA) third-degree burns. OFR was determined in the blood of patients with electron spin resonance (ESR). S/W ratio and tau c values of patients' erythrocytes were measured with ESR spectrometer. Blood superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) activities, malondialdehyde contents and plasma endotoxin levels were assayed. Rats were sacrificed at the 12th, 24th, 48th and 72nd hour after injury. Plasma endotoxin levels, mucosal SOD, GSHPx and malondialdehyde (MDA), as well as diamine oxidase activity of ileum were determined. Cultures of mesenteric lymph nodes (MLN), liver, spleen, heart, lung, kidney and blood were done. RESULTS: A significant increase in blood OFR contents and plasma MDA, and a significant decline in blood SOD and GSHPx were found after resuscitation in DR group as compared with those in ER group. Both strong to weak spectra component (S/W) ratio and tau c value were higher in DR group in contrast with those in ER group. Higher elevation in plasma endotoxin level in DR group was seen. In DR group, plasma MDA content was correlated with S/W ratio, tau c value and plasma endotoxin level. In rats, the level of mucosal MDA, plasma endotoxin and incidence of bacterial translocation (BT) were significantly higher. Mucosal SOD, GSHPx and diamine oxidase (DAO) activity were significantly lower in DR group as compared with those in ER group. In DR group, mucosal MDA content was negatively correlated with mucosal DAO activity, while the latter was negatively correlated with BT. After treatment with vitamins E and C, mucosal MDA content decreased, plasma endotoxin and BT significantly declined and mucosal DAO heightened. CONCLUSIONS: Tissue reperfusion might induce the production of OFR, resulting in lipid peroxidation injury, especially to intestinal mucosa, and resulting in disruption of mucosal barrier function followed by endotoxemia and BT.     

Identification of hepatitis B virus-DNA in the liver by in situ hybridization using a biotinylated probe. Relation to HBcAg expression and histology

The cellular localisation of hepatitis B virus (HBV)-DNA in liver tissue was studied by in situ hybridisation using biotinylated and radiolabelled probes on samples from HBsAg carriers with a spectrum of disease and related to the presence of HBV-DNA in serum and intrahepatic HBcAg expression. Sixteen of the 31 patients studied were seropositive for HBV-DNA; nine had chronic active hepatitis and seven had chronic persistent hepatitis. HBV-DNA was detected in the liver tissue in seven of these patients. In each, HBV-DNA was detected in both cytoplasm and nuclei. All seven also had nuclear and/or cytoplasmic HBcAg which in six was associated with chronic active hepatitis. HBcAg (without tissue HBV-DNA) was detected in the remaining nine patients with an exclusively nuclear pattern in two. Fifteen patients were seronegative for HBV-DNA. HBV-DNA was not detected in the tissue of any of these. Three of these were HBcAg positive but in each this was confined to occasional nuclei and each had inactive disease. The close association between the presence of detectable HBV-DNA in tissue, cytoplasmic HBV-DNA expression and chronic active hepatitis in one group and a failure to detect HBV-DNA in those with nuclear HBcAg and benign disease suggests that there may be two distinct patterns of HBV replication in chronic HBV carriers which may influence the development of liver damage.     

Intracellular calcium, currents, and stimulus-response coupling in endothelial cells

Vascular endothelium appears to be a unique organ. It not only responds to numerous hormonal and chemical signals but also senses changes in physical parameters such as shear stress, producing mediators that modulate the responses of numerous cells, including vascular smooth muscle, platelets, and leukocytes. In many cases, the initial response of endothelial cells to these diverse signals involves elevation of cytosolic Ca2+ and activation of Ca(2+)-dependent enzymes, including nitric oxide synthase and phospholipase A2. Both the release of Ca2+ from intracellular stores, most likely the endoplasmic reticulum, and the influx of Ca2+ from the extracellular space contribute to the [Ca2+]i increase. The most important trigger for Ca2+ release is inositol 1,4,5-trisphosphate, which is generated by the action of phospholipase C, a plasmalemmal enzyme activated in many cases by the receptor-G protein cascade. Ca2+ influx appears to be related to the activity of receptor-G protein-enzyme complex and to the degree of fullness of the endoplasmic reticulum but does not involve voltage-gated Ca2+ channels. The magnitude of the Ca2+ influx depends on the electrochemical gradient, which is modulated by the membrane potential, Vm. Under basal conditions, Vm is dominated by a large inward rectifier K+ current. Some stimuli, e.g., acetylcholine, have been shown to hyperpolarize Vm, thus increasing the electrochemical gradient for Ca2+, which appears to be modulated by activation of Ca(2+)-dependent K+ and Cl- currents. However, the lack of potent and specific blockers for many of the described or postulated channels (e.g., nonselective cation channel, Ca(2+)-activated Cl- channel) makes an estimation of their effect on endothelial cell function rather difficult. Possible future directions of research and clinical implications are discussed.     

Aspects of 5-alpha reductase deficiency, a review

Two forms of 5 alpha-reductase deficiency have been described and two genes have been cloned. In view of the psychoendocrinological complexity of the primary form, the early diagnosis preferably in infancy, is crucial. Rearing up those who are assigned as females to the male gender identity could minimize the risk of gender identity and role disorders when puberty is reached.     

Striatal [18F]fluorodopa utilization after COMT inhibition with entacapone studied with PET in advanced Parkinson's disease

The effect of peripheral catechol-O-methyltransferase (COMT) inhibition with entacapone on striatal uptake of 6-[18F]fluoro-L-dopa (FDOPA) was studied with PET both without and with entacapone in fifteen advanced parkinsonian patients and six healthy controls. Entacapone significantly enhanced the fraction of unmetabolized FDOPA in plasma from 16% to about 50% at 80 minutes after FDOPA injection in all subjects. The striatal to occipital ratios and the striatal FDOPA uptake, expressed as a modified decarboxylation coefficient (k3R0), was significantly increased in healthy controls, whereas in parkinsonian patients the increase was significant only in the caudate. On the other hand, the influx constant (Ki) decreased significantly in the caudate and putamen in parkinsonian patients; in healthy controls the Ki remained virtually unchanged. Effective peripheral COMT inhibition markedly increased the fraction of FDOPA in plasma and thus its availability in the brain for decarboxylation both in patients and control subjects. However, the change in striatal FDOPA uptake was modest in the advanced parkinsonian patients as compared to that in control subjects, because of the advanced disease, decreased storage capacity, or both.     

Glutathione S-transferases in esophageal cancer

Glutathione content and glutathione S-transferase enzyme activity as well as isoenzyme composition were studied in normal gastric cardia, normal squamous esophageal epithelium and corresponding malignant tumor of 10 patients with esophageal cancer. Mean values of glutathione (38 +/- 6 versus 36 +/- 12 nmol/mg protein) and glutathione S-transferase activity (532 +/- 44 versus 532 +/- 108 nmol/min mg protein) did not differ significantly between normal esophageal and tumor tissue. However, great individual differences exist. In two patients, glutathione S-transferase activity was much higher in the tumor (1081 and 1381 nmol/min mg protein) due to overexpression of class alpha, mu and pig glutathione S-transferases in one case, and of class mu and pi in the other case. In the other patients, glutathione S-transferase activity was equal (one case) or lower (seven cases) in the tumor. In normal gastric cardia glutathione content as well as glutathione S-transferase activity was significantly lower as compared to normal esophageal epithelium. In conclusion, in contrast to other gastrointestinal tumors, glutathione S-transferases are overexpressed in esophageal tumors in only a limited number of patients.     

Immunohistochemical characterization of the plasminogen activator system in psoriatic epidermis

The relative topographical distribution of urokinase-type plasminogen activator (uPA), tissue-type PA (tPA), PA-inhibitor-1 (PAI-1), PA-inhibitor-2 (PAI-2), plasmin(ogen), alpha 2-antiplasmin, and alpha 2-macroglobulin was studied in lesional epidermis of psoriasis vulgaris, and in normal epidermis, by immunohistochemistry. In psoriatic epidermis, tPA predominated, although uPA was found in some biopsies. PAs were not detected in normal epidermis. PAI-1 was not detected in normal epidermis and was only present in a proportion of biopsies of psoriatic lesions. PAI-2 was found in normal and psoriatic epidermis. Plasmin(ogen) was confined to the basal cell layer of normal epidermis, whereas in lesional psoriatic skin it was scattered throughout the epidermis. Alpha 2-antiplasmin and alpha 2-macroglobulin were not found in the epidermis of normal skin. In psoriatic epidermis alpha 2-antiplasmin was confined to the subcorneal layer, whereas staining for alpha 2-macroglobulin was found only in a proportion of biopsies, in the upper epidermis. Our immunohistological findings indicate that colocalization of tPA and its substrate plasminogen may allow efficient generation of plasmin, and that the focal absence of plasmin inhibitors may then favour the persistence of plasmin activity.