Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Millions of people have been exposed to silicones because of the widespread use in consumer products such as cosmetics and toiletries, food products, household products and paints. Silicones have wide use in medical practice, including lubricants in tubing and syringes, and as implantable devices. The most prevalent silicone in medical use is polydimethylsiloxane. This study was undertaken to determine the subchronic immunotoxicologic potential of the principal constituents of breast implants: silicone fluid, silicone gel and silicone elastomer. An alternative covering for devices containing silicone gels, polyurethane, was also included in the study. Silicone fluid and gel were injected subcutaneously into female B6C3F1 mice (1 ml/mouse) and 6 mm disks of silicone elastomer or polyurethane were implanted subcutaneously. There were no treatment-related deaths or overt signs of toxicity. None of the tested materials had notable effects on body or organ weights, erythrocytes or leukocytes in the blood, blood chemistries such as alanine aminotransferase, urea nitrogen, glucose, albumin or total protein. The cellularity of the bone marrow and responses to CSF-GM and CSF-M were normal. The tested silicones did not alter the distribution of B cells and T cells in the spleen, but polyurethane perturbed the distribution of CD4+CD8+ and CD4-CD8- T cells. The antibody response to sheep erythrocytes was not markedly altered, nor were proliferative responses to concanavalin A, phytohemagglutinin, lipopolysaccharide or allogeneic cells. Reticuloendothelial function was normal, but polyurethane evoked an enhanced phagocytosis of Covaspheres by adherent peritoneal cells. Natural killer cell activity and serum complement were not altered. All silicone materials afforded modest protection to a challenge with Listeria monocytogenes that killed 40 to 58% of control mice. Host resistance to Streptococcus pneumoniae or the B16F10 tumor was not affected by any of the treatments. There is a pattern indicative of some perturbation of T cell differentiation in mice implanted with a polyurethane disk.
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PMID:Subchronic 10 day immunotoxicity of polydimethylsiloxane (silicone) fluid, gel and elastomer and polyurethane disks in female B6C3F1 mice. 798 83

Millions of people have been exposed to silicones which are present in consumer goods such as cosmetics and toiletries, processed foods and household products. In addition, silicones have been used extensively in medical practice as a lubricant in tubing and syringes, and as implantable devices. A silicone widely used in medical practice is polydimethylsiloxane. This study was undertaken to determine the immunotoxicologic potential of long term exposure to the principal constituents of breast implants: silicone fluid, silicone gel and silicone elastomer. An alternative covering for devices containing silicone gels, polyurethane, was also included in the study. Silicone fluid and gel were injected subcutaneously into female B6C3F1 mice (1 ml/mouse) and 6 mm disks of silicone elastomer or polyurethane were implanted subcutaneously. There were no treatment-related deaths or overt signs of toxicity during the 180 day exposure. None of the tested materials had notable effects on body or organ weights, erythrocytes or leukocytes in the blood, blood chemistries such as alanine aminotransferase, urea nitrogen, glucose, albumin or total protein, or serum CH 50 or C3 levels. The cellularity of the bone marrow and responses to CSF-GM and CSF-M were normal. The tested silicones and polyurethane marginally reduced the level of Ig+ cells in the spleen but did not consistently alter the distribution of T cell surface markers. The antibody response to sheep erythrocytes was not markedly altered, nor were proliferative responses to concanavalin A, phytohemagglutinin, lipopolysaccharide or allogeneic cells. Reticuloendothelial function was normal, as was phagocytosis of chicken erythrocytes and Covaspheres by adherent peritoneal cells. Natural killer cell activity was depressed in all silicone treatment groups and in mice implanted with polyurethane. No silicone or polyurethane treatment group displayed altered susceptibility to a challenge with Listeria monocytogenes, Streptococcus pneumoniae or the B16F10 tumor. The only consistent effect of 180 day exposure to silicone materials or polyurethane was a modest depression of natural killer cell activity.
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PMID:Immunotoxicity of 180 day exposure to polydimethylsiloxane (silicone) fluid, gel and elastomer and polyurethane disks in female B6C3F1 mice. 798 84

Recombinant human granulocyte-macrophage colony-stimulating factor is being used to improve the immunological function of patients with various diseases and to ameliorate hematological disorders. We investigated the tolerance and possible antiviral effect of the administration of daily doses of recombinant human granulocyte-macrophage colony-stimulating factor (3, 1 or 0.5 micrograms/kg body wt) to nine patients with chronic hepatitis B, alone or in combination with 5 MU interferon-alpha 2b. Recombinant human GM-CSF reduced significantly (p < 0.02) hepatitis B virus DNA levels. The three doses used were equally effective. Of the eight patients who completed the study, four became negative for HBV DNA and HBeAg; two of them seroconverted to HBe antibody. These four patients showed improvement in the histological activity of their liver disease. Ultimately, two patients regained normal ALT values. 2',5'-Oligoadenylate synthetase activity increased significantly (p < 0.01) in cell lysates of mononuclear cells cultured in vitro, coinciding with the reductions in hepatitis B virus DNA levels. Recombinant human granulocyte-macrophage colony-stimulating factor was well tolerated but produced a dose-dependent increase in white blood cell counts. It became intolerable at doses of 3 micrograms (and was reduced to 1.5 microgram); this effect was reversible after cessation of recombinant human granulocyte-macrophage colony-stimulating factor treatment. No remarkable variations occurred in other parameters. In conclusion, recombinant human granulocyte-macrophage colony-stimulating factor administration is safe and tolerable at doses of 0.5 to 1 microgram/kg body wt and may exert an antiviral effect in chronic hepatitis B.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pilot study of recombinant human granulocyte-macrophage colony-stimulating factor in the treatment of chronic hepatitis B. 840 50

We report a 56-year-old man who developed progressive paraparesis. He was apparently well, except for left Bell's palsy which developed on May 9 of 1994, for which he received stellate ganglion block on the left side more than ten times until July 2nd of 1994, when he noted pain in his left shoulder and in his lumbar region. On July 5th, he noted some difficulty in urination. On July 6th, he noted tingling sensation in his four extremities and difficulty in gait. He was admitted to another hospital where he was treated with intravenous infusion of glycerol. After this treatment, his gait and sensory disturbance showed some improvement, however, on July 7th, his shoulder and lumbar pain worsened, and he became unable to stand. His temperature went up to 39 degrees C on the next day. Lumbar CSF on that day contained 119 cells/microliters, 112 mg/dl of protein, and 53 mg/dl of sugar. He was transferred to our hospital on July 14th. His past medical history revealed that he had suffered from frequent bouts of osteomyelitis since the age of 13 years. He was operated on several times on osteomyelitis. He had been treated on his tooth ache until shortly before the onset of the present illness. He also received steroid hormone for his Bell's palsy. On admission, his consciousness varied from alert to stupor. His BP was 150/100 mmHg, HR 98/min and regular, BT 39.4 degrees C. The bulbar conjunctiva appeared somewhat icteric. Otherwise, general physical examination was unremarkable. On neurologic examination, there was no apparent dementia. Higher cerebral functions appeared intact. The optic discs were flat. Pupils were round and isocoric reacting to light and accommodation promptly. Ocular movements were full without nystagmus. Some exophthalmos was noted bilaterally. The sensation of the face and facial muscles were intact. The remaining cranial nerves also appeared intact. Nuchal rigidity was present. He was unable to stand or walk. Muscle strength was markedly diminished in all four limbs; manual muscle testing revealed 1 to 2/5 weakness in both upper and lower extremities bilaterally. Muscle stretch reflexes were decreased or lost in both upper and lower limbs, but the plantar response was extensor on the right. Sensation appeared to be diminished in legs, but detail was not clear because of disturbance of consciousness. Pertinent laboratory findings were as follows: WBC 12,800/microliter, GPT 58 IU/l, total bilirubin 2.65 mg/dl, and CRP 16.8 mg/dl. Cerebrospinal fluid contained 34 cells/microliter (approximately two thirds were neutrophils), RBC 1,110/microliter, 2,949 mg/dl of protein, and 119 mg/dl of glucose; stapylococcus aureus was cultured from the CSF. Myelogram showed a filling defect in the anterior epidural space between the low thoracic and the upper lumbar region. The patient was treated with cephotaxim, aminobenzyl penicillin, and chloramphenicol. On the second hospital day, his BT was still 39 degrees C and he was agitated His weakness was worse than the previous day. Spinal MRI was attempted; as he was agitated 5 mg of diazepam was given intravenously at 4 PM. His respiration was rapid and somewhat shallow. At 6 PM, gadolinium DTPA was injected intravenously; at that time, he was breathing and pupils were 3 mm on both sides. At 6:35 PM, an examiner noted that he stopped breathing; the left pupil was dilated to 5 mm. Cardiopulmonary resuscitation was initiated immediately, and intubation was performed. He was placed on a respirator. His blood pressure did not reach 100 mmHg; he was in deep coma. Cardiac arrest occurred at 8:53 AM on the next morning. The patient was discussed in a neurological CPC. Most of the participants thought that the patient had either spinal epidural empyema or spinal subdural abscess. The question was what might be the original focus of infection. Three possibilities were considered, i.e., stellate ganglion block, teeth infection, and osteomyelitis...
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PMID:[A 56-year-old man with fever, backache and tetraparesis]. 896 86

CSF samples were taken from 50 healthy pigs of both sexes and cytologically and biochemically examined. With the aid of regression calculations it was investigated, whether deep freezing of CSF samples influences the laboratory results. The parameters glucose, urea, creatinine, total protein, magnesium, anorganic phosphate, AST and AP were in good agreement with the values of the original samples exhibiting only slight variations. Minor age relationship was only seen with respect to the two enzymes LDH and HBDH. A linear relationship was found between values in CSF and in serum of the parameters urea, creatinine, sodium and potassium. CSF examination should include cell count, Pandy's test and bacteriological investigation as well as the determination of the levels of the enzymes LDH and HBDH. The activity of the enzymes AST and ALT increases along with the severity of the tissue damage (meningitis). The specific gravity increases similarly to the total protein level in cases of chronic compression of the spinal cord, and Pandy's test becomes positive. However, CSF glucose levels are partly reduced in animals with central nervous symptoms. The levels of the enzymes AP and CK are often increased in central nervous disturbances, but do not admit drawing a conclusion on the degree of damage.
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PMID:[The cerebrospinal fluid from healthy pigs and pigs with central nervous system diseases]. 901 21

An open label trial of GM-CSF plus high-dose interferon (IFN) alpha 2b was performed in eight patients with chronic hepatitis B infection and 16 patients with chronic hepatitis C, who either failed to clear virus with 6 months of daily high-dose IFN (5 MU daily) therapy (n = 22) or were considered untreatable because of advanced disease and leukopenia (n = 2). The dose of GM-CSF used was 500 micrograms subcutaneously twice weekly. The dose of IFN used was 5 MU daily. Both agents were administered for 4 months. Five of the eight hepatitis B patients and five of the 16 hepatitis C virus patients responded to combined therapy having previously failed IFN therapy alone. The hepatitis B virus responders had low entry ALT, AST, and gamma GPT levels as compared to the non-responders. No such differences for responders and non-responders were seen with the hepatitis C virus patients. These data suggest that the combination of GM-CSF and IFN may be more effective at achieving viral clearance than IFN alone.
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PMID:A preliminary experience with GM-CSF plus interferon in patients with HBV and HCV resistant to interferon therapy. 909 87

After intracranial tumour surgery edema, ischaemic and haemorrhagic changes are developing in the brain. It causes leakage of certain intracellular components and enzymes into extracellular and cerebrospinal fluid. This study includes 46 patients operated on for cerebral tumours. Lumbar CSF was obtained in postoperative course and the activity of AST, ALT, LDH, alpha HBDH, CK, gamma GT and oxygen concentration were estimated. In the control group were 10 patients suffering from sciatic pain and CSF was obtained during radiculography. For diagnostic and prognostic purposes of biochemical markers statistical analyse methods were employed and comparisons with clinical factors were carried out. In conclusions we suggest that enzymes AST, alpha HBDH, CK and oxygen content give valuable additional information of postoperative brain damage.
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PMID:[Enzymatic activity in cerebrospinal fluid in the monitoring of the brain lesions following intracranial tumors]. 976 May 54

A retrospective clinical study of 64 cases with bacterial meningitis beyond the neonatal period in the department of pediatrics of St. Mary's Hospital (1985-1995) was conducted. Haemophilus influenzae (H. influenzae) (28 cases, 43.8%) and Streptococcus pneumoniae (S. pneumoniae) (23 cases, 35.9%) were common pathogens. The prognosis was classified into three groups; normal (42 cases, 65.6%), neurological sequelae (17 cases, 26.6%) and death (5 cases, 7.8%). We analyzed the risk factors associated with their outcome. The body temperature at admission, platelet count, CSF examination (WBC, glucose, GOT, GPT) were prognostic factors. The prognosis of bacterial meningitis caused by S. pneumoniae was worse than those due to H. influenzae (p = 0.0347).
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PMID:[Risk factors for clinical prognosis in bacterial meningitis beyond the neonatal period]. 978 May 79

Overdose of acetaminophen (APAP) causes severe centrilobular hepatic necrosis in humans and experimental animals. Here, to explore its mechanism, we administered APAP at subtoxic (150 mg/kg ip) and toxic (500 mg/kg ip) doses to overnight fasted mice. Animals were sacrificed at different time points from 15 min to 4 h postinjection. We assessed liver toxicity by plasma ALT activity and by electron microscopy. Using nylon filter arrays and RTQPCR, we performed genomics analysis in liver. We ran proteomics on liver mitochondrial subfractions using the newly developed quantitative fluorescent 2D-DIGE method (Amersham Pharmacia Biotech UK Limited). As soon as 15 min postinjection, centrilobular hepatocyte mitochondria were already slightly enlarged and GSH total content dropped by a third at top dose. GM-CSF mRNA, which is a granulocyte specific gene likely coming from resident Kupffer cells, was also induced to its maximum of 3-fold at both doses. Chaperone proteins Hsp10 and Hsp60 were readily decreased by half in mitochondria at both doses, most likely by leaking into cytoplasm. Although APAP is known as an apoptotic trigger, no apoptosis was observed at any time point. Most of the protein changes in mitochondria were present at 15 min postinjection, thus preceding most of the gene regulations. The decrease of ATP synthase subunits and beta-oxidation pathway proteins indicated a loss of energy production. As the morphology of mitochondria was also affected very early at top dose, we concluded that APAP toxicity was a direct action of its known reactive metabolite NAPQI, rather than a consequence of gene regulation. However, the latter will either worsen the toxicity or lead toward cell recovery depending on the cellular damage level.
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PMID:Genomics and proteomics analysis of acetaminophen toxicity in mouse liver. 1175 93

Levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and creatine kinase (CK) were estimated in serum and cerebrospinal fluid of 25 patients of stroke, and were correlated with severity of disease. 21 (84%) patients had ischemic stroke and four (16%) had hemorrhagic stroke. Serum and CSF AST levels were significantly elevated in the study group. The rise in CSF AST was more in the hemorrhagic subtype than in the ischemic subtype. Serum ALT and CSF LDH levels were also significantly elevated in patients with ischemic stroke. None of the enzyme levels were related to the severity of disease as assessed by the Glasgow coma scale.
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PMID:Evaluation of enzymes in serum and cerebrospinal fluid in cases of stroke. 1257 13


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