Axial spatial distribution focusing: improving MALDI-TOF/RTOF mass spectrometric performance for high-energy collision-induced dissociation of biomolecules.

Rationale: For the last two decades, curved field reflectron technology has been used in matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometers, assisting in the generation of post-source-decay (PSD) or collision-induced dissociation (CID) without decelerating precursor ions, producing true high-energy CID spectra. The result was the generation of product ion mass spectra with product ions typical of high-energy (10 keV and beyond) collision processes. The disadvantage of this approach was the lack of resolution in CID spectra resulting from the excess laser energy deposition used to generate those MS/MS spectra.

Dissociation of biomolecules using a ultraviolet matrix-assisted laser desorption/ionisation time-of-flight/curved field reflectron tandem mass spectrometer equipped with a differential-pumped collision cell.

A commercial matrix-assisted laser desorption/ionisation time-of-flight (MALDI-ToF) instrument equipped with a curved field reflectron (CFR) was modified in order to perform collision-induced dissociation (CID) on a variety of biomolecules. The incorporation of a high-resolution ion gate together with a collision cell within the field-free region allowed tandem mass analysis (MS/MS), without the necessity to decelerate the precursor ions prior to activation. The simultaneous detection of all product ions remained possible by using the CFR.

Ultrastructural pathology and cytochemical investigations of L-2-chloropropionic acid-induced neurointoxication of the rat cerebellum.

The objectives of the studies described were to assess the ultrastructural neuropathology, blood-brain barrier (BBB) integrity and calcium status of the cerebellum of rats following a single dose of 750 mg.kg-1 L-2-chloropropionic acid (L-2-CPA). The first indications of intoxication appeared at 36 h when condensation of many granule cells associated with Purkinje cell degeneration and marked astroglial swelling were observed.

Aortic atherosclerosis and stroke.

Methods: Studies using transesophageal echocardiography (TEE) suggest aortic atherosclerosis may be a risk factor for stroke, particularly stroke of undetermined mechanism, but controls in prior studies were not balanced for vascular risk factors. We used TEE to evaluate aortic atherosclerosis in 60 patients with stroke compared with a high-risk control population of 46 subjects. We also examined the possible association of plasma viscosity and fibrinogen levels to aortic atherosclerosis.

Assessment of the labeling index of cohorts of the anterior pituitary cell population in phenobarbital-treated male rats by a double immunohistochemical technique for bromodeoxyuridine and pituitary hormones.

A previous study demonstrated that administration of phenobarbital for up to 7 days to male AP Wistar rats caused alterations in labeling indices (LIs) of several different tissues as determined by immunohistochemical visualization of bromodeoxyuridine (BrdU) incorporation into S-phase nuclei. The pivotal role of the pituitary gland in the function of the endocrine system and changes in circulating hormone levels that result from administration of xenobiotics prompted our consideration of the possible changes in LIs of individual cohorts of the anterior pituitary cell population that may occur as a specific functional adaptation during phenobarbital administration. We evaluated the LIs of individual anterior pituitary cell cohorts by modifying a double immunohistochemical staining method for bromodeoxyuridine and pituitary hormones using a sequential peroxidase-anti-peroxidase (PAP)/alkaline phosphatase-anti-alkaline phosphatase (APAAP) method employing diaminobenzidine and New Fuchsin chromogens, respectively.

Pathological and morphometric assessment of testicular parameters in patients with metastatic prostate cancer following treatment with either the antiandrogen Casodex (ZM176,334) or bilateral orchidectomy.

Casodex is an orally active non-steroidal antiandrogen that is highly selective for androgen receptors in animals and man. It is indicated for the non-surgical treatment of advanced prostate cancer in man. The present open controlled study in 13 Casodex-treated and 21 orchidectomy-alone (control) patients addressed the hypothesis that chronic administration of antiandrogens will result in Leydig cell hyperplasia as a result of feedback inhibition of the pituitary resulting in increased luteinising hormone (LH) stimulation of Leydig cells.

Assessment of the labelling index of cohorts of the pancreatic islet cell population in phenobarbitone-treated male rats using a double immunohistochemical technique for 5-bromo-2'-deoxyuridine and pancreatic hormones.

A previous study demonstrated that administration of phenobarbitone to male AP Wistar rats for up to 7 days caused alterations in labelling indices (LIs) in several different tissues (including a reduction of the endocrine pancreas population LI) as determined by immunohistochemical visualisation of 5-bromo-2'-deoxyuridine (BrdU) incorporation into S-phase nuclei. The primary objective of this study was to determine whether treatment with phenorbarbitone influenced the replicative states of specific cohorts of the islet (of Langerhans) cell population or generated a uniform depression of LI. Quantitation of the LIs of individual islet cell cohorts was achieved by utilisation of a dual immunohistochemical staining method for BrdU and islet hormones (insulin, glucagon and somatostatin) using a sequential peroxidase anti-peroxidase (PAP)/alkaline phosphatase anti-alkaline phosphatase (APAAP) method employing diaminobenzidine and New Fuchsin chromogens, respectively.

Retrosigmoid transmeatal approach: an anatomic study of an approach used for preservation of hearing in acoustic neuroma surgery and vestibular neurotomy.

The limitations of the transmeatal phase of the retrosigmoid transmeatal approach are shown, and the problems of opening the internal acoustic meatus via this approach and the criteria for its use are discussed.

The morphological and immunohistochemical analysis of renal biopsies by light and electron microscopy using a single processing method.

A methodology is described in which a number of well-established research techniques are brought together to enable the complete diagnostic analysis of a renal biopsy on a single piece of tissue. By embedding the biopsy in the acrylic resin LR White, unsupported sections of which are stable in the electron beam, light and electron microscopy and immunocytochemistry become feasible on sections from the same block. The biopsy is glutaraldehyde fixed but post-fixation in osmium tetroxide, which is often deleterious to antigen preservation, is omitted.

Chronic relapsing thrombotic thrombocytopenic purpura.

A 58-year-old man had anemia and thrombocytopenia immediately after a myocardial infarction; recovery occurred spontaneously, but relapses followed intercurrent infection and abdominal surgery. The terminal relapse was precipitated by gastric ulcer with hemorrhagic gastritis; this episode was characterized by fluctuating neurologic symptoms including coma. Autopsy studies confirmed the diagnosis of thrombotic thrombocytopenic purpura.

The effect of donor age on the flow properties of blood. Part I: Plasma and whole blood viscosity in adult males.

The relationship between blood viscosity and age was studied using heparinized blood samples obtained from 50 normal male blood donors between the ages of 20 and 65 years. There was a slight but significant decline in packed cell volume (hematocrit) with age. Plasma viscosity showed no significant variation with donor age, but the viscosity of blood samples standardized to a packed cell volume of 45 ml/dl showed an increase as the age of the donor rose.

Abrogation of calcium exclusion by erythrocytes under hypotonic stress.

Normal human erythrocytes in isotonic suspension maintain a high gradient of calcium ion concentration across the membrane, with the cytosol [Ca2+] several orders of magnitude below plasma concentration. Despite the high degree of exclusion maintained against the entry of Ca2+, the osmotic resistance of red cells in hypotonic saline is significantly augmented by the presence in the medium of Ca2+ in concentrations greater than 0.07 mmol/l.

Age as a factor affecting erythrocyte osmotic fragility in males.

Osmotic fragility and erythrocyte dimensions were measured in 40 normal males between the ages of 18 and 78 years. The principal independent variables correlating with osmotic fragility were mean cell haemoglobin concentration and the age of the donor. The age-related effect was shown to increase both the mean fragility of the cells and the variability of the fragilities of the cells within the individual blood sample.

The modification of human erythrocyte membrane structure by membrane stabilizers: an electron spin resonance study.

Membrane structure in intact human erythrocytes was analyzed by electron-spin-resonance (ESR) spectroscopy. The spin probes 5-doxyl stearate and 5-doxyl stearate methyl ester revealed thermally-induced structural transitions in the membrane at 37 degree C and 15 degree C. The addition of propranolol, diazepam, chlorpromazine, or Pluronic F68 all caused a decrease in the temperature of the upper transition, but did not markedly alter the temperature of the lower transition.

Pseudoleukemia: when "leukemia" is not leukemia.

Several case reports6-8 in the literature have pointed out that a clinical and morphologic picture resembling that of acute leukemia may be secondary to infection or use of toxic drugs or alcohol. In these cases, the leukemic picture spontaneously returns to normal when the precipitating factor is no longer present. This condition has been termed pseudoleukemia.

Therapy with factor IX concentrate resulting in DIC and thromboembolic phenomena.

The development of subclinical DIC in a patient with factor IX hemophilia receiving concentrate replacement therapy during surgery is discussed with respect to pertinent laboratory features. Subsequent thromboembolic phenomena are presented in the context of current literature. Of significance is the failure of heparin given with the factor IX concentrate to prevent DIC.

The role of the spleen and splenectomy in autoimmune hemolytic disease.

The relationship of the spleen to the red cell in AHDW is determined by the characteristics of the surface protein coating of the red cell, rather than by a pathologic change in the reactivity of the spleen. The behavior of the spleen is essentially a passive response to red cells with abnormal properties. The critical properties are incompletely defined, but probably include cell shape, and perhaps more importantly, the intrinsic properties of the cell membrane.

Human blood group activity of human and canine intestinal glycolipids containing fucose.

A number of fucose-containing glycolipids (fuco-lipids), which are similar in composition to those of human normal and malignant gastrointestinal tissue, have been isolated from whole small intestines of individual dogs. Dogs from which these fuco-lipids were isolated fell into two types according to the qualitative sugar composition of their fuco-lipids. Glycolipids from type I dogs contained glucose, galactose, glucosamine, galactosamine and fucose, while those from type II dogs contained the same sugars but lacked galactosamine.