Plasminogen activators and plasminogen activator inhibitors in neural development.
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Animals↗
Biomedical subjects
B Gardner
Publications and source records attributed to B Gardner.
Evidence that the antigens of the Yt blood group system are located on human erythrocyte acetylcholinesterase.
The Yt blood group system comprises two antigens, Yta and Ytb. Human anti-Yta and human anti-Ytb immune precipitate a component of the same apparent molecular weight as acetylcholinesterase from radioiodinated erythrocytes of appropriate Yt phenotype. Immune precipitates obtained with anti-Yta and anti-Ytb contained acetylcholinesterase activity. In contrast, immune precipitates obtained with human anti-Gya and murine monoclonal anti-CD55, which identify other glycosylphosphatidylinositol-linked erythrocyte surface proteins, did not have acetylcholinesterase activity. Quantitative binding assays using murine monoclonal antiacetylcholinesterase antibodies (AE-1 and AE-2) gave 3,000 to 5,000 binding sites/cell for IgG and 7,000 to 10,000 sites/cell for Fab fragments. Endo F digestion of immune precipitates obtained with AE-1 and anti-Yta indicated that approximately 10% of the enzyme comprises N-glycans. These results indicate that the Yt antigens define an inherited polymorphism on erythrocyte acetylcholinesterase and that the recent assignment of the Yt blood group locus to the long arm of chromosome 7 (Zelinski et al, Genomics 11:165, 1991) provisionally identifies the position of the acetylcholinesterase gene.
Acetylcholinesterase↗
It won't close--now what?
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Abdominal Muscles↗
The hepatic artery--a guide to major upper abdominal resections.
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Abdomen↗
En bloc caudate lobe and partial vena cava resection using a Gott shunt for retrohepatic caval bypass.
A technique of retrohepatic inferior vena cava bypass is described, useful for resection of the hepatic caudate lobe. A 77 year old female developed a solitary metastatic tumor mass in the caudate lobe compressing the Inferior Vena Cava (IVC), with cavography showing the IVC to be compressed, but patent. Without evidence of other metastatic disease radical resection of this tumor was performed. Successful resection was accomplished using a Gott shunt and porta hepatus compression for hepatic vascular isolation. No pump was used to avoid heparinization. Postoperative imaging confirmed IVC patency. The serum carcinoembryonic antigen (CEA) level fell to normal and remained so for 18 postoperative months. This introduces a new use of an atriocaval shunt for hepatic isolation during resection.
Aged↗
Complications of intrathecal baclofen delivery.
The medical records of 46 consecutive patients who have had intrathecal Baclofen drug delivery systems implanted in the National Spinal Injuries Centre, the Paddocks Hospital Spinal Unit, Princes Risborough, Lodge Moor Hospital Spinal Unit, Sheffield, the Northern Regional Spinal Injuries Unit, Hexham and The Radcliffe Infirmary, Oxford, were reviewed. Patients were contacted to describe their views on the treatment. The complications of the treatment are described. Some, such as overdose and meningitis are particularly hazardous. Others, in particular pump tubing revisions, are more of an inconvenience and time consuming for the patient and physician. If the serious risks of this valuable treatment are to be minimized and the therapy applied most effectively than a well co-ordinated team is essential, involving in particular the physician responsible for the initial assessment and follow-up of the patient and an experienced surgeon. It is recommended that only a small number of centres in the UK undertake these implants.
Adolescent↗
New monoclonal antibodies in CD59: use for the analysis of peripheral blood cells from paroxysmal nocturnal haemoglobinuria (PNH) patients and for the quantitation of CD59 on normal and decay accelerating factor (DAF)-deficient erythrocytes.
CD59 is a widely expressed cell surface glycosylphosphatidylinositol (GPI)-linked glycoprotein which acts as an inhibitor of the assembly of the membrane attack complex of autologous complement. Four new monoclonal antibodies to CD59 (2/24, 1B2, BRIC 229, BRIC 257) are described. Competitive binding experiments using these antibodies, two known CD59 antibodies (MEM-43, YTH 53.1) and a previously described antibody LICR-LON-Fib75.1 demonstrated that all seven antibodies see related epitopes on human erythrocyte CD59. In common with other GPI-linked proteins, CD59 (as defined by antibody 2/24) was sensitive to treatment with phosphatidylinositol-specific phospholipase C (PI-PLC) on lymphocytes and monocytes but not on erythrocytes. Flow cytometric analysis using antibody 2/24 identified two populations (CD59 positive and CD59 deficient) of lymphocytes, monocytes and erythrocytes in peripheral blood from a patient with paroxysmal nocturnal haemoglobinuria (PNH). The abundance of CD59 on normal erythrocytes was determined as 21,000 copies/cell when radioiodinated BRIC 229 was used. Other CD59 antibodies gave values of 10,000 (IF5) and 15,000 (2/24) against the same target cells. Radioiodinated Fab fragments of BRIC 229 gave a value of 39,000 copies/cell. Erythrocytes from two individuals with a rare inherited deficiency of decay accelerating factor (DAF), known as the Inab phenotype, expressed normal levels of CD59.
Antibodies, Monoclonal↗
Ability of unstimulated and phorbol-ester-stimulated human blood-monocyte-derived macrophages to metabolize drugs and its implications.
Solutions containing 5,5-diphenyl[4-14C]hydantoin (15 micrograms/ml) or pheno[2-14C]barbital (20 micrograms/ml) were incubated for 0.5-6 h with monolayers of unstimulated and phorbol-ester-stimulated human blood-monocyte-derived macrophages and suspensions of K562 cells. The incubated solutions were centrifuged and the cell-free supernatants subjected to chromatography on Q-Sepharose Fast Flow anion exchange resin. The interaction with unstimulated macrophages but not with K562 cells resulted in a time-dependent conversion of the original radioactive drug molecules to molecules with a larger negative charge in the case of diphenylhydantoin and a smaller negative charge in the case of phenobarbital. These conversions were prevented by 20 mM tetrahydrofurane and partially inhibited by 300 U/ml superoxide dismutase (SOD) and, therefore, appeared to depend on cytochrome-P-450-mediated reactions and to some extent also on superoxide anion radicals. Macrophages which were stimulated by 20 nM phorbol myristate acetate metabolized both drugs at much faster rates than unstimulated macrophages. Since this increased metabolism was abolished in the presence of SOD, it appeared to be entirely dependent on superoxide anion radicals. These data provide biochemical evidence that unstimulated human monocyte-derived macrophages have a substantial capacity to metabolize certain xenobiotics and that stimulated macrophages have an even greater capacity to do so. This property of macrophages may have considerable biological significance and be important in the pathogenesis both of drug-induced tissue damage and of malignant disease.
Chromatography, Ion Exchange↗
New monoclonal antibodies in CD44 and CD58: their use to quantify CD44 and CD58 on normal human erythrocytes and to compare the distribution of CD44 and CD58 in human tissues.
The cell-surface glycoproteins CD44 and CD58 are involved in cell adhesion reactions. In this paper 12 monoclonal antibodies in CD44 and two in CD58 are described. Competitive binding assays using CD44 antibodies identified three distinct epitope groups. Antibodies in Group 1 and, with one exception (BRIC 214), antibodies in group 2, but not antibodies in Group 3, recognized epitopes that are sensitive to reduction and to trypsin or chymotrypsin treatment of intact erythrocytes, and so these epitopes probably reside on the N-terminal disulphide-bonded domain of CD44. Antibodies in CD44 did not inhibit the binding of CD58 antibodies to erythrocytes or vice versa. Quantitative binding studies using radioiodinated IgG measured 1888-5592 copies of CD44 and 1772-3290 copies of CD58 on normal erythrocytes. Similar measurements with radioiodinated Fab fragments gave values of 6508-10,450 (CD44) and 3457-7622 (CD58). Immunocytochemical studies indicated that CD44 is much more widely expressed in non-haemopoietic tissues than CD58. Comparison with previously described CD44 antibodies suggests that antibodies in our Group 1 encompass Hermes 2 and that those in Group 2 encompass Hermes 1. All the CD44 antibodies gave weakened reactions with Lu(a-b-) erythrocytes of the In(Lu) type by one or more methods. BRIC 214 and antibodies in epitope Group 3 were used to demonstrate that CD44 on these variant cells gives membrane-bound trypsin and chymotrypsin cleavage fragments of similar molecular weight to those obtained with normal erythrocytes.
Antibodies, Monoclonal↗
A comparison of hospital costs and morbidity between octogenarians and other patients undergoing general surgical operations.
The hospital costs and clinical results of 304 patients who were more than 80 years old and who underwent general surgical procedures were evaluated. The over-all mortality rate was 14 per cent; 19.9 per cent occurred in patients admitted under emergency conditions as compared with 8.9 per cent that occurred in patients undergoing elective procedures (p less than 0.001). Seventy-nine per cent of the patients were discharged and 7 per cent required care in a skilled nursing facility. Survival rates were as good or better than standard life table survival rates for 80 year old patients. Costs were higher in those who were admitted under emergent conditions or who died in the hospital. Deaths were a result of complications of the primary disease rather than associated disease in most groups. Neither costs nor length of stay could accurately predict survival of individual patients. We concluded that health resources should be directed at treating problems, such as cholelithiasis, hernia or carcinoma, early before complications develop.
Actuarial Analysis↗
Relationship of race to functional status among breast cancer patients after curative surgery.
Analysis of functional status of 197 breast cancer patients three years after curative radical mastectomy indicated a cumulative probability of disability of 25%, whereas the probability of death regardless of prior disability was 40.5%. Analysis of functional status by patient characteristics indicated that nonwhites were three times more likely than whites to experience disability (P less than 0.01) as defined in terms of their ability to carry on normal activities without assistance. Although whites and nonwhites were diagnosed at similar stages of disease, nonwhites were, on average, eight years younger than whites. They younger age may reflect a larger proportion of premenopausal breast cancer cases among nonwhites, which if associated with more rapidly progressing disease could account for their poorer prognosis. Alternatively there may exist factors in the nonwhites' social or economic environment that limited the ability of the family to care for the patient at home. These data reaffirm the need to monitor closely breast cancer patients to diagnose acute complications, and they indicate that most patients can resume normal activities shortly after curative surgery.
Activities of Daily Living↗
Reaction between the isolated globular sub-units of the complement component C1q and IgG-complexes.
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Amino Acids↗
Local duodenal metastasis from colonic carcinoma.
The clinical and radiologic appearance of an isolated metastasis to the duodenum may mimic a primary pancreatic or duodenal cancer. As lymphatics from the right colon drain to periduodenal lymph nodes, lymphatic spread from right colon cancer can cause enlargement of the duodenal loop, with ulceration or distortion of the mucosa on the medial aspect of the duodenum. We present three patients with ulcerating metastases in the duodenum from colon cancer whose cases exemplify the problems of diagnosis and management.
Adenocarcinoma↗
Fibromatosis of the breast.
A case of fibromatosis of the breast occurring in a 37-year-old woman is described. Only 15 cases of this type have been previously reported. In 5 of these cases there was also involvement of the underlying pectoral muscles, raising the possibility that some of these may have been of pectoral musculoaponeurotic origin. Two of the previously reported cases occurred in patients with Gardner's syndrome and 1 in a patient with "familial muticentric fibromatosis." It is anticipated that fibromatosis of the breast will behave in a similar fashion to fibromatosis occurring in other sites; i.e., as a local aggressive lesion which exhibits a high incidence of local recurrence following incomplete excision.
Adult↗
The relationship of cholecystectomy and taurocholic acid feeding to bile composition and hepatocyte function in prairie dogs.
The prairie dog was used as a model for human gallstone formation. Stones formed in the gallbladder of all animals on a lithogenic diet. Hepatic bile was nonlithogenic, whereas gallbladder bile promoted cholesterol precipitation. Addition of taurocholate to the diet reduced the number of stones and lithogenicity. Cholecystectomy resulted in an increased bile flow and reduced secretion of cholesterol in the animals on a high cholesterol diet. Reduction of cholesterol and bile acid synthesis by negative feedback was demonstrated in isolated hepatocyte culture. The shift of bile salt production to chenodeoxycholates on a high cholesterol intake was demonstrated both in vivo and in vitro. A theory of gallstone formation is presented which hypothesizes a defect in hepatocyte storage of cholesterol rather than bile acid synthesis as the primary effect, relegating the problems to one of a disease of lipid metabolism.
Animals↗
Treatment of hepatic metastases with a combination of hepatic artery infusion chemotherapy and external radiotherapy.
Systemic chemotherapy has given good results when compared with that of patients who received no chemotherapy. When resection was performed, the results are slightly better. The group of patients who underwent combined therapy, using infusion chemotherapy, radiation and systemic chemotherapy, had the best results. It appears that infusion chemotherapy and radiotherapy can improve the palliation available for patients with metastases in the liver from carcinoma of the colon and rectum and warrants further investigation.
Adult↗
The reaction between the complement subcomponent C1q, IgG complexes and polyionic molecules.
The strength of the bond between 125I-labelled C1q and immune complexes, Fc piece, dextran sulphate, polyglutamic acid and polylysine has been investigated. The binding of C1q to Fc piece, small molecular weight (less than 10,000) dextran sulphate, polyglutamic acid and polylysine have value; for the functional affinity constant (Ko) in the range of 0.2-1.5 X 10(4) M-1. In contrast the binding of C1q to immune complexes and large molecular weight polyions (greater than 100,000 is much greater and lies in the range 3 X 10(7)--4 X 10(8) M-1. The differences in the binding constants between the two groups can be explained if the Fc piece and small molecular weight compounds bind to only 1 head of the C1q molecule but the immune complexes and large molecules bind to 2 heads. There are probably 6 binding sites on the C1q molecule for dextran sulphate. The enhancement of the binding affinity of C1q by reduction in ionic strength and the reaction with polyions, indicate that ionic groups are present near or within the binding sites.
Antigen-Antibody Complex↗