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PubMed1984

The neuroleptic syndrome and central dopamine metabolites.

The neuroleptic malignant syndrome remains an intriguing syndrome, yet its pathogenesis is unknown. Despite numerous analogies with peripheral disorders of aberrant calcium migration in the sacroplasmic reticulum, the probable loci are striatal and hypothalamic (preoptic) dopaminergic pathways. In order to clarify the characteristics of dopamine activity, analysis of the central metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid in one case revealed marked elevations. A possible role for postsynaptic dopamine receptor inhibition is discussed. These findings further suggest that the syndrome may be similar to other extrapyramidal disorders, and they lend credence to observations of its reported drug induction and management.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1982

Correlation of circulating levels of a serum protein with triiodothyronine levels and hepatoma growth.

In this communication, we provide evidence that proliferation of transplantable Morris hepatoma 7777 might to some extent be regulated by triiodothyronine and/or a specific serum protein, the levels of which are correlated with levels of triiodothyronine. The protein has an estimated molecular weight of 80,000 and migrates as one band on polyacrylamide gel electrophoresis. In normal rats, this protein accounts for approximately 1% of the total serum protein. Both the circulating levels of the serum protein and proliferating of transplanted hepatoma cells were decreased in thyroidectomized rats. Elevated levels of the serum protein and increased cell proliferation were observed when animals had 70% of their lives removed prior to transplant, were given injections of triiodothyronine, or had a 10-day-old first transplant surgically removed. Some evidence is also provided suggesting that the synthesis of the serum protein is stimulated by thyroid hormone.

Animals↗

PubMed1996

Effect of vitamin A deficiency on the early response to experimental Pseudomonas keratitis.

PURPOSE: Vitamin A-deficient humans and animals are more susceptible to infections than are healthy humans and animals. This study compares the early corneal response (within 24 hours) to an experimental Pseudomonas aeruginosa infection between vitamin A deficient and control rats. METHODS: Male WAG/Rij/MCW rats were fed either a vitamin A- deficient diet (A-) or the same diet with retinyl palmitate added back in a nonrestricted manner (N) or under pair-fed conditions (A+) to yield weight-matched rats. Some A-rats were repleted wih retinyl palmitate 16 days before being killed and then given free access to the retinyl palmitate-supplemented diet (R). Twenty-four hours before being killed, the corneas of anesthetized rats were scratched and P. aeruginosa organisms were applied to the corneal surface. The rats were killed using an overdose of sodium pentobarbital. Corneas were either processed for light and electron microscopic examination or extracted for proteinase and myeloperoxidase determination. Corneal myeloperoxidase concentrations relative to neutrophil myeloperoxidase concentrations were used to determine the number of neutrophils in the cornea. Zymography was used to study caseinases, gelatinases, and plasminogen activators. Reverse zymography was used to detect proteinase inhibitors. Similar results were noted at early, mid, and late weight plateau stages of vitamin A deficiency. RESULTS: Ulceration occurred within 24 hours when low numbers of P. aeruginosa (10(4) cpu) were applied topically onto scratched A- corneas, whereas no ulceration was observed in the A+, R, and N corneas. When higher numbers of P. aeruginosa (10(7)-10(8)) were applied to the scratched corneas, all corneas became ulcerated within 24 hours. The extent of ulceration in the control corneas was greater than that in A- corneas by a factor of two. Only the A- corneas contained inflammatory cells with unusual striated deposits in phagolysosomes. The total number of neutrophils in the cornea and the concentrations of caseinases, plasminogen activators, and gelatinases in the infected corneal extracts were similar; however, the concentrations of cysteine proteinase inhibitors were elevated under A- conditions. CONCLUSIONS: Vitamin A deficiency alters the response of the cornea to a P. aeruginosa infection during the first 24 hours. The alterations observed are probably due to multiple factors: an insufficient tear film for bacterial clearance and migration of neutrophils, epithelial keratinization, alterations in corneal wound healing, and changes in polymorphonuclear function.

Animals↗

PubMed1997

[An autopsy case of pulmonary thromboembolism: a delayed complication of a victim by traffic accident].

A 35-year-old male had fallen down from his motor bike caused a fracture of the medial condyle of the right tibia and the acromion of the left scapula. He had received screw fixed operation for his right tibia and had been in the hospital for one month. He died suddenly in the hospital and was autopsied to find out the cause of death. On external examination, it was found that affected leg was bruised and swollened. Partially organized thrombosis in the posterior tibial vein was revealed and bilateral pulmonary arteries were packed with reddish massive thromboemboli. The causes of the posterior tibial vein thrombosis were intimal damage and decreased venous flow, attributable to bed rest for long days and external fixation of the lower extremity. We presumed that direct cause of death was a large thromboemboi which were migrated from posterior tibial vein and lodged at the bifurcation of the pulmonary artery causing obstruction of pulmonary blood flow. Finally we opened the direct cause of death was pulmonary thromboembolism due to leg injury. Clinical instability may hinder the diagnostic elevation and delay therapeutic intervention, it is the most often happened in sudden death cases within the hospital. The importance of early diagnosis and early prevention is underscoped, because the symptoms of pulmonary thromboembolism are not always produced. To prevent fatal pulmonary thromboembolism in trauma, prophylactic use of low-dose heparin therapy and/or the use of oral anticoaglant (warfarin) have been effective and recommended in USA and Western Europe. The routine use of these therapy has not yet been spread in Japan, because the incidence is still apparently lower than in USA and Western Europe as well as the risk of hemorrhage. If the victims of road traffic accident receive the prophylactic use of low-dose heparin and/or oral anticoaglant (warfarin), it might be an effective way to reduce mortality.

Accidents, Traffic↗

PubMed1998

Alterations in peripheral blood leukocytes functions during enzootic bronchopneumonia of calves. Effect of treatment with antibiotics and immunomodulators.

Twelve calves from over veal calf farm were divided into two groups: group I-6 calves which developed typical signs of enzootic bronchopneumonia and group II-6 calves with no symptoms of the disease. Both groups of calves were compared with respect to changes in several hematological parameters. Some functions of peripheral blood leukocytes as random migration, phagocytic index, percent of phagocytic cells and percent of NBT positive cells were also scored. In addition, changes in serum levels of interferon (IFN) and tumor necrosis factor (TNF) and the ability of peripheral blood leukocytes (PBL) to produce IFN and TNF were quantitated by biological methods. On the day of diagnosis, in group I of calves a significant increase in the total serum protein concentration, hemoglobin content, red and white blood cells counts in comparison to control calves (group II) was observed. The increased number of NBT positive neutrophils and moderate levels of serum IFN and TNF correlated with elevated body temperature, breathing and heart rates. Calves with bronchopneumonia (group I) after diagnosis of the disease were treated with Tylbian (tylosine derivative), Flumetazon (glucocorticoid), Emulselvet (immunomodulator), bromhexinum and sulphonamides. Seven days after the beginning of treatment with medicaments a significant improvement in clinical symptoms was observed, however, the ability of PBL to cytokine production increased significantly 2 weeks after beginning of treatment and correlated with significant increase in random migration of neutrophils and their phagocytic activity, measured by the percent of phagocytic cells. Unexpectedly, in control calves (group II), not exhibiting any symptoms of bronchopneumonia at the beginning of experiment, high serum IFN titers were detected which decreased significantly during the first week of observation. In contrast to that the ability of PBL of control calves to produce IFN increased significantly within 3 weeks of observation. The correlations between the ability of PBL to produce cytokine and the development of clinical symptoms of bronchopneumonia are discussed.

Adjuvants, Immunologic↗

PubMed2005

Gene expression profiling of mouse postnatal cerebellar development using oligonucleotide microarrays designed to detect differences in glycoconjugate expression.

Differences in gene expression patterns between adult and postnatal day 7 (P7) mouse cerebellum, at the peak of granule neuron migration, were analyzed by hybridization to the GLYCOv2 glycogene array. This custom designed oligonucleotide array focuses on glycosyl transferases, carbohydrate-binding proteins, proteoglycans and related genes, and 173 genes were identified as being differentially expressed with statistical confidence. Expression levels for 11 of these genes were compared by RT-PCR, and their differential expression between P7 and adult cerebellum confirmed. Within the group of genes showing differential expression, the sialyltransferases (SiaTs) and GalNAc-Ts that were elevated at P7 prefer glycoprotein substrates, whilst the SiaTs and GalNAc-Ts that were elevated in the adult preferentially modify glycolipids, consistent with a role for gangliosides in maintaining neuronal function in the adult. Also within this group, three proteoglycans--versican, bamacan and glypican-2--were elevated at P7, along with growth factor midkine, which is known to bind to multiple types of proteoglycans, and fibroblast growth factor receptor 1, whose activity is known to be influenced by heparan sulfate proteoglycans. Two sulfotransferases that can modify the extent of proteoglycan sulfation were also differentially regulated, and may modify the interaction of a subset of proteoglycans with their binding partners during cerebellar development. Bamacan, glypican-2 and midkine were shown to be expressed in different cell types, and their roles in cerebellar development during granule neuron migration and maturation are discussed.

Aging↗

PubMed1976

alpha1-Microglobulin, a new low molecular weight plasma protein.

A new low molecular weight protein was purified from the urine of uraemic patients. The protein was found to be glycoprotein with a molecular weight of 31 500, determined by SDS-polyacrylamide gel electrophoresis, and a carbohydrate content of 19%. It was electrophoretically heterogenous and migrated in the slow alpha1-region. The mean serum level in 20 apparently healthy individuals was 32+/-10 mg/1. The serum level was normal in 5 patients with severe reduction of plasma protein synthesis caused by cirrhosis of the liver but elevated in patients with a decreased glomerular filtration rate. The mean urinary excretion in 5 healthy individuals was 1.3 mg/24 h. Increased excretion was seen in 10 patients with varying degrees of uraemia.

Amino Acids↗

PubMed1989

Immunoglobulins from the sera of immunologically activated persons with pairs of electrophoretic restricted bands show a greater tendency to aggregate than normal.

From in vitro data, it has been speculated that pairs of endogenous restricted bands migrating in close proximity in the gamma region upon high resolution serum electrophoresis (HRE) represent circulating immune complexes (CIC). Using a polyethylene glycol (PEG) method to separate CIC, we found a very high correlation between the presence of such band pairs and elevated levels of CIC (CHI2 = 25.7, p less than 0.001) in 51 sera. HRE appears to be a good screening technique to identify, with a high degree of certainty, samples with elevated levels of CIC for delineation by more specific methods. Yet, examination by gel-filtration chromatography and precipitation with PEG indicated that the molecules comprising the band patterns were not CIC, but polyclonal 7S IgG. These bands are usually found in patients with chronic activation of the immune system. Fractionation of the sera from 5 such patients with various cuts of PEG indicated that the average IgG concentration in the 2.5-5%, and 5-7.5% cuts from patients was 3.99 g/l and 2.2 g/l, while from healthy subjects the concentrations were 0.68 g/l and 2.88 g/l. This reversed precipitation pattern was seen both for absolute levels of IgG and for percent of total IgG. On the average the amount of precipitation of IgG in the 2.5-5% fraction of patients was about 5-fold above that seen in the healthy subjects. The endogenous bands were not associated with any specific cut of PEG, but appeared to be proportionally distributed in accord with the levels of IgG. The data is consistent with the idea that immunologically activated patients exhibit a greater tendency for immunoglobulins to associate than normal. This propensity to aggregate may cause CIC to form in situ in local compartments even though CIC do not appear to be present upon analysis by biochemical techniques.

Antigen-Antibody Complex↗

PubMed1979

Use of 2-mercaptoethanol to facilitate detection and classification of IgM abnormalities by immunoelectrophoresis.

IgM immunoglobulins in elevated serum concentrations have a tendency to polymerize and form aggregates. When subjected to immunoelectrophoreses these proteins may deposit at the point of origin. This can result in failure to detect an IgM abnormality or the masking of other serum protein abnormalities migrating near the area of application. This paper demonstrates the importance of using reducing agents such as 2-mercaptoethanol not only to detect and/or to confirm the monoclonal IgM gammopathies but also to unmask other protein abnormalities.

Bence Jones Protein↗

PubMed2006

Expression of adhesion molecular proteins in the cochlear lateral wall of normal and PARP-1 mutant mice.

Sound can damage peripheral cochlear function through a number of mechanisms, and emerging evidence suggests that inflammation may be one of them. Using immunohistochemistry and poly (ADP-ribose) polymerase-1 (PARP-1) mutant mice, we tested whether PARP-1 contributes to loud-sound induced cochlear lateral wall damage by triggering inflammatory effects, including upregulating intercellular adhesion molecule-1 (ICAM-1), P-selectin and platelet-endothelial cell-adhesion molecule-1 (PECAM-1). In control conditions, we found that there was no detectable poly-ADP-ribose (PAR) in the marginal cells and microvessels. ICAM-1 was expressed only at low levels in the vessels of the stria vascularis and the spiral ligament. P-selectin and PECAM-1 were barely detected and only in the vessels of the spiral ligament. Following loud-sound exposure, PAR was detected in numbers of marginal cells and some vessels of the spiral ligament. Also, an elevated expression of ICAM-1 was demonstrated in some vessels of the stria vascularis and spiral ligament. Increased expression of P-selectin and PECAM-1 were mainly located in the vessels of the spiral ligament, while increased populations of non-migrated and migrated leukocytes were observed in the area of the spiral ligament. However, neither increased expression of adhesion proteins nor increased population of leukocytes, were observed in the PARP-1 knockout mouse. We thus conclude that loud-sound stress activates the expression of adhesion molecular proteins in the lateral wall and that PARP-1 modulates inflammation-linked protein expression and leukocyte migration.

Animals↗

PubMed1992

Severe metallosis due to abnormal abrasion of the femoral head in a dual bearing hip prosthesis. A case report.

The authors report on a patient with a case of severe metallosis due to an abnormal abrasion of the femoral head. A primary arthroplasty was performed using a dual bearing hip prosthesis with acetabular bone grafting by ceramic screws. At the time of the revision surgery the synovia was black, and an analysis using a scanning electron microscope and scanning electron microscope-electron probe micro-analyzer revealed numerous small particles of small alumina ceramic on the inner surface of the bearing insert of high-density polyethylene. These particles, which came from the broken ceramic screws due to proximal migration of the prosthesis, scraped the femoral head away. A line and area analysis of the black synovia revealed that the synovia contained metal particles of a cobalt-chromium alloy as well as a cobalt ion. The patient's serum showed elevated concentrations of cobalt, chromium, and molybdenum that dramatically reduced 2 months after the revision surgery.

Adult↗

PubMed1996

Titanemia from total knee arthroplasty. A case resulting from a failed patellar component.

The subject of this case report is a patient with elevated serum levels of titanium (77 parts/billion [ppb]; normal, 3.3 ppb) and vanadium (0.38 ppb; normal, 0.17 ppb) resulting from excessive wear of a metal-backed patellar component in a total knee arthroplasty. The patellar component was worn through both its polyethylene and metal backing as a result of abnormal contact between the patellar and femoral components. Scanning electron microscopic examination of the ingrowth surface of the patellar component indicated that particle debonding occurred as a result of overloading of the sintered neck regions at the particle-substrate interface, suggesting a possible damage during initial insertion of the device, which may have predisposed it to loosening and abnormal contact with the femoral component. Wear particles resulted in staining of the tissues within the knee and an inflammatory and immune response in the synovium consisting of giant cells and T lymphocytes. The serum metal levels were reduced 22 weeks after replacing the patellar component; however, the titanium level was still slightly elevated (8 ppb).

Aged↗

PubMed2004

Complexes of the heavier alkaline Earth metals Ca, Sr, and Ba with O-functionalized phosphanide ligands.

Metathesis reactions between either SrI(2) or BaI(2) and 2 equiv of the potassium phosphanide [[(Me(3)Si)(2)CH]-(C(6)H(4)-2-OMe)P]K yield, after recrystallization, the complexes [[([Me(3)Si](2)CH)(C(6)H(4)-2-OMe)P](2)M(THF)(n)] [M = Sr, n = 2 (5); Ba, n = 3 (6)]. Similar metathesis reactions between MI(2) and 2 equiv of the more sterically demanding potassium phosphanide [[(Me(3)Si)(2)CH](C(6)H(3)-2-OMe-3-Me)P]K yield the chemically isostructural complexes [[([Me(3)Si](2)CH)(C(6)H(3)-2-OMe-3-Me)P](2)M(THF)(2)] [M = Ca (9), Sr (7), Ba (8)]. Compounds 5-9 have been characterized by multi-element NMR spectroscopy and X-ray crystallography. Complex 9 is thermally unstable and decomposes at room temperature to give the tertiary phosphane [(Me(3)Si)(2)CH](C(6)H(3)-2-OMe-3-Me)P(Me) and an unidentified Ca-containing product. Compounds 5 and 6 also decompose at elevated temperatures to give the corresponding tertiary phosphane [(Me(3)Si)(2)CH](C(6)H(4)-2-OMe)P(Me) and intractable metal-containing products. The decomposition of 5, 6, and 9 suggests that these compounds undergo an intramolecular methyl migration from the O atom in one phosphanide ligand to the P atom of an adjacent phosphanide ligand to give species containing dianionic alkoxo-phosphanide ligands.

Journal Article↗

PubMed2001

Upregulation of collagen VIII following porcine coronary artery angioplasty is related to smooth muscle cell migration not angiogenesis.

Type VIII collagen is upregulated after vessel injury, and this collagen has been implicated in both smooth muscle cell migration and angiogenesis. This study examines the temporal and spatial pattern of expression of type VIII collagen in porcine coronary vessels at specific time points after balloon angioplasty. In situ hybridization studies demonstrated that collagen VIII messenger ribonucleic acid (mRNA) was markedly elevated in the neoadventitia at 3 days post-angioplasty. By 14 days, elevated collagen VIII message was seen mainly in the neointima and this expression decreased to background levels by 90 days. The distribution of collagen VIII protein, detected using immunohistochemistry, was similar but the up-regulation lagged behind the mRNA increase by a few days. Pre-treatment of sections with pepsin highlighted variations in the organization and appearance of extracellular collagen VIII containing structures in both injured and normal vessels. New vessel formation was evident in the neoadventitia after 3 days, but there was no colocalization of type VIII collagen immunostaining with that of von Willebrand factor (a marker of endothelial cells) in the neoadventitia. These data show that up-regulation of collagen VIII in the neoadventitia is an important early marker of the coronary arterial response to injury, and is not associated with new vessel formation.

Angioplasty, Balloon, Coronary↗

PubMed1995

Bispecific monoclonal antibodies for intravenous treatment of carcinoma patients: immunobiologic aspects.

Immunobiologic parameters measured during a phase I trial of intravenously (i.v.) administered bispecific monoclonal antibodies (BsmAb) in renal cell carcinoma (RCC) patients are described. The BsmAb used, BIS-1, is reactive with a pancarcinoma-associated 38 kDa transmembrane glycoprotein, EGP-2, as well with the CD3 complex. Patients received during a 2 h i.v. infusion F(ab')2 fragments of BIS-1 at doses of 1, 3, or 5 micrograms/kg body weight during concomitantly applied subcutaneous (s.c.) IL-2 treatment. Acute but transient BIS-1 F(ab')2-related toxicity was observed at the 3 and 5 micrograms/kg dose level, and the maximum tolerated dose (MTD) was set at 5 micrograms/kg. A dose-dependent binding of BIS-1 F(ab')2 to circulating T lymphocytes was found. The in vivo occupancy of CD3 molecules on T lymphocytes was highest at teh end of the infusion period and then rapidly decreased, as shown by flow cytometry. A much slower decrease of BIS-1 F(ab')2 binding was observed in vitro, suggesting migration of BIS-1 F(ab')2-loaded T lymphocytes from the circulation. A strong but transitory leukopenia was observed, in which LFA-1 alpha bright, CD3/CD8 double positive T cells left the circulation preferentially. This phenomenon was most likely induced by elevated TNF-alpha and IFN-gamma plasma levels, which were at a maximum shortly after the end of the infusion. Isolated peripheral blood mononuclear cells obtained from patients directly after treatment with BIS-1 F(ab')2 at the 3 and 5 micrograms/kg dose level showed increased EGP-2-directed antitumor activity.

Antibodies, Bispecific↗

PubMed1981

Quantitation of sperm population migration: capillary scanning assay.

Bulk sperm migration through capillaries containing experimental media was quantitated by use of a recording spectrophotometer equipped with a linear transport. The method was applied to human semen and caudal epididymal sperm samples from hamster, rat, rabbit, and bull. The rate of migration of a given sperm population was approximately 1/10 that of the velocities previously reported for individual sperm of that species. This matched theoretical approximations based upon assumptions of random orientation and multiple, direction-changing collisions for individual cells. The rate of migration for undiluted caudal epididymal sperm populations into Tyrode's solution for all species tested showed an initial burst followed by a slower, more linear rate. Predilution or prewashing the sperm samples eliminated the initial burst in hamster and rabbit sperm but elevated migratory rates in bull sperm. Human sperm populations diluted by ejaculation also exhibited no initial burst but maintained a strong linear rate down the capillaries.

Animals↗

PubMed1999

A rationale for treatment of endothelial dysfunction in hypertension.

Strategically located between the circulating blood and the vascular smooth muscle, endothelial cells release numerous vasoactive substances that regulate the function of vascular smooth muscle and circulating blood cells. Important endothelium-derived vasodilators are prostacyclin, bradykinin, nitric oxide (NO) and, independent of the former, endothelium-derived hyperpolarizing factor. In particular, NO inhibits cellular growth and migration. In concert with prostacyclin, NO exerts potent antiatherogenic and thromboresistant properties by preventing platelet aggregation and cell adhesion. These effects are counterbalanced by vasoconstrictors, angiotensin II and endothelin-1, both of which exert prothrombotic and growth-promoting properties. In hypertension, elevated blood pressure transmits into cardiovascular disease by causing endothelial dysfunction. Hence, modern therapeutic strategies in human hypertension focus on preserving or restoring endothelial integrity. Calcium antagonists counteract angiotensin II and endothelin-1 at the level of vascular smooth muscle by reducing the inflow of Ca2+ and facilitating the vasodilator effects of NO. Besides inhibiting the renin-angiotensin system, angiotensin-converting enzyme inhibitors diminish the inactivation of bradykinin, leading to an augmented release of NO. Newly developed vasopeptidase inhibitors induce potent antihypertensive effects in low-, normal-, and high-renin models of hypertension, not only because of the decreased breakdown of natriuretic peptides, but also because of the inhibition of endothelin-1 generation. Furthermore, experimental studies suggest that endothelin antagonists effectively lower blood pressure and prevent target-organ damage in salt-sensitive forms of hypertension. Further clinical studies are already underway to examine whether restoring endothelial dysfunction results in a clinical benefit in hypertension.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1999

Chemotaxis of rat mast cells toward adenine nucleotides.

Rat mucosal mast cells express P2 purinoceptors, occupation of which mobilizes cytosolic Ca2+ and activates a potassium conductance. The primary function of this P2 system in mast cell biology remains unknown. Here, we show that extracellular ADP causes morphological changes in rat bone marrow-cultured mast cells (BMMC) typical of those occurring in cells stimulated by chemotaxins, and that the nucleotides ADP, ATP, and UTP are effective chemoattractants for rat BMMC. ADP was also a chemotaxin for murine J774 monocytes. The nucleotide selectivity and pertussis toxin sensitivity of the rat BMMC migratory response suggest the involvement of P2U receptors. Poorly hydrolyzable derivatives of ADP and ATP were effective chemotaxins, obviating a role for adenosine receptors. Buffering of external Ca2+ at 100 nM or reduction of the electrical gradient driving Ca2+ entry (by elevating external K+) blocked ADP-driven chemotaxis, suggesting a role for Ca2+ influx in this process. Anaphylatoxin C5a was a potent chemotaxin (EC50 approximately 0.5 nM) for J774 monocytes, but it was inactive on rat BMMC in the presence or absence of laminin. Ca2+ removal or elevated [K+] had modest effects on C5a-driven chemotaxis of J774 cells, implicating markedly different requirements for Ca2+ signaling in C5a- vs ADP-mediated chemotaxis. This is supported by the observation that depletion of Ca2+ stores with thapsigargin completely blocked migration induced by ADP but not C5a. These findings suggest that adenine nucleotides liberated from parasite-infested tissue could participate in the recruitment of mast cells by intestinal mucosa.

Adenine Nucleotides↗