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Biomedical subjects

G Hamilton

Publications and source records attributed to G Hamilton.

At least 253 records · Page 14Linked to original sources
PubMed1988

Natural killer cell activities of patients with breast cancer against different target cells.

Natural killer (NK) cell activity against K 562 erythroleukemic- and MCF-7 breast carcinoma-derived cells was monitored in short-term (3 h/K 562) and long-term (18 h/MCF-7) chromium release tests for 60 patients with untreated primary breast disease. Target cell lysis was the same for patient groups with benign (n = 13) and malignant (n = 47) breast disease (27% versus 36% mean chromium release; target:effector ratio 40:1 for K 562 and 28% versus 40% for MCF-7 cells). NK activity as defined by short-term lysis of K 562 cells did not correlate with MCF-7 cell lysis in long-term assays for the carcinoma patients. This functional heterogeneity of natural cytotoxic activities of breast cancer patients was confirmed by a different age distribution for K 562 and MCF-7 cell lysis and high levels of MCF-7-directed NK activity in the grade I tumor group (56.2%). Our results indicate that measurement of peripheral blood NK activity against a breast carcinoma-derived cell line (MCF-7) defines a disease-related natural cytotoxic activity which correlates better with prognostic tumor parameters (tumor grading) than NK activity as defined by the lysis of K 562 erythroleukemic cells. NK activity testing against breast carcinoma cell lines should be used to monitor natural cytotoxic activities in breast cancer patients and its modulation by different routes of treatment.

Adult↗
PubMed1988

Influence of two glutamine-containing dipeptides on growth of mammalian cells.

The instability of the amino acid glutamine prompted us to investigate substitute compounds appropriate for culture conditions. The effect of two glutamine-containing dipeptides, alanylglutamine (Ala-Gln) and glycylglutamine (Gly-Gln), on the growth behavior of a hematopoietic cell line in culture (K562) was investigated. Growth rates and [3H]thymidine incorporation rates of cells cultivated in sterile-filtrated media, containing glutamine (Gln) or Ala-Gln or Gly-Gln, were not statistically different. Although heart-sterilization of media containing Gln caused approximately 95% decomposition of the Gln, both dipeptides remained unaltered. Consequently, cell growth was drastically decreased when autoclaved free Gln-containing media were used, but growth was unaffected in the presence of autoclaved dipeptides. Both Ala-Gln and Gly-Gln have an advantage over free Gln as growth factors for cell culture due to the stability of the dipeptides during both autoclaving and storage; the biological activity, however, is comparable.

Cell Division↗
PubMed1988

Impaired cell-mediated immunity in the first week after burn injury: investigation of spontaneous blastogenic transformation, PHA, IL-2 response and plasma suppressive activity.

This study investigated alterations of cell-mediated immunity induced by trauma, operative treatment and infections in a group of 19 burned patients with a mean burn size of 42 +/- 22 per cent of the body surface area. We tested peripheral mononuclear blood cells (PMBC) for spontaneous blastogenic transformation (SBT), phytohaemagglutinin (PHA) and interleukin-2 (IL-2) responsiveness. Plasma samples were also assayed for inhibition of mitogen stimulation of control PMBCs. Mean values were calculated for the acute postburn period (days 0-3) and the following 4 days, before the development of septic complications. SBT was significantly increased in all patients during the second period of investigation (days 4-7) in comparison to normal controls and during the acute phase. The response to mitogen stimulation (PHA) was significantly suppressed during days 0-7 and the plasma samples showed high suppressive activities following PHA stimulation of control lymphocytes during the course of the study. No significant differences in rates of SBT, PHA responsiveness and plasma suppressive activity were found between those patients who developed bacteraemia and those with negative blood cultures. The latter group showed higher reactivity to added IL-2 in comparison to normal controls. Surgical treatment immediately after trauma (fasciotomy; day 0 or 1) resulted in further increased immunosuppression (PHA and IL-2 response), whereas after necrectomy (days 4-7) the immunological parameters showed no significant differences. It can be concluded that neither rates of SBT nor response to PHA can be used to identify patients at high risk for infection during the first week postburn.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Prediction of aneurysm formation in vascular grafts of biologic origin.

Other than review of clinical experience, no assay exists that can reliably predict the long-term potential for aneurysm formation in an arterial prosthesis of biologic origin. Since mural degeneration probably results from proteolytic digestion, an in vitro assay was devised that used graft perfusion with 1% collagenase to induce rapid changes in mechanical properties. The effect of enzyme on graft diameter, compliance, permeability, and burst pressure was measured in ficin-digested, adipoyl chloride and glutaraldehyde-tanned bovine carotid artery and glutaraldehyde-tanned human umbilical vein. Both grafts have recently been reported to have a significant incidence of aneurysm within several years of implantation. Compliance and diameter were also measured noninvasively in patients with bovine carotid artery and human umbilical vein for more than 40 weeks after implantation. In vitro, the response to enzyme could be categorized into three groups. In group III, a diameter increase of more than 14% was associated with a significantly decreased compliance, and this paralleled the results found in aneurysmal grafts in vivo. In both grafts there was a strong correlation between postenzyme compliance change and initial compliance, loss of compliance being significantly greater in grafts with group III responses (p less than 0.01). This response may be a good predictor of a graft's overall susceptibility to aneurysmal degeneration, and initial compliance measurement may effectively identify inadequate fixation. Thus measurement of compliance may prove useful in quality control of a fixation process used in mass production. In conclusion, measurement of mechanical properties of biologic vascular grafts before and after collagenase exposure forms the basis for an effective in vitro assay of aneurysm susceptibility.

Aneurysm↗
PubMed1988

Influence of leupeptin on protein and amino-acid metabolism in septic rats.

We investigated the influence of leupeptin (LP) intraperitoneal injection (40 mumol/2 days) on protein and amino-acid metabolism of septic rats (cecal ligation). All septic rats lost weight (-17 +/- 4 g), which was not prevented by LP administration (-24 +/- 1.8 g, n.s.). LP injection evoked weight loss even in normal rats (p less than 0.05 vs controls). Weight loss was accompanied by enhanced urinary nitrogen losses in all three groups. LP reduced food intake for 47% in control rats. Cecal ligation, and also the administration of LP, led to alterations of amino-acid metabolism. The most important changes were found in muscle free amino-acid concentrations with highly decreased levels of free glutamine. A glutamine deficiency is known to be related to a decreased rate of protein synthesis. The proteolytic rate in incubated soleus muscle was increased for 11.5% and even higher in LP-treated septic rats (+22%). It is concluded that the administration of LP cannot reverse protein catabolism in sepsis--possibly because LP does not influence those enzymes or proteases involved in tissue loss, or LP is inactivated by enzymes in rat tissues.

Amino Acids↗
PubMed1987

Mechanistic consequences of charge transfer systems in serine proteases and angiotensin: semiempirical computations.

Structures and relative energies for the triads of interacting groups in the serine charge relay system of serine proteases and the proposed tyrosine charge relay system of angiotensin II, respectively, were computed according to the standard MNDOC procedure. The most stable configuration obtained for both systems was one in which the histidine residue was negatively charged. These findings indicate that the histidine ring and not the serine hydroxyl group at the active site of serine proteases would be the nucleophilic center which is acylated by substrate. Similarly, the extreme nucleophilicity of the imidazole anion produced by the proposed triad of interacting groups in angiotensin could provoke the formation of a transient covalent bond (acyl intermediate) between receptor and peptide in the receptor activation mechanism.

Angiotensin II↗
PubMed1987

[Toxicity results of an adjuvant study with intraperitoneal chemotherapy in patients with stomach cancer. Current status and future prospects of intraperitoneal therapy].

The peritoneum is a frequent location of recurrent disease after surgical treatment of carcinoma of the stomach, colon, rectum or ovary. Usually this type of recurrence does not respond very well to systemic chemotherapy. The rational of intraperitoneal (ip) perfusion with cytotoxic drugs is based on a 2- to 3-log-fold increase in ip level over plasma concentration for certain chemotherapeutic agents. Hence, malignant cells in the peritoneal cavity can be exposed to very high concentrations of cytotoxic agents without serious systemic side effects. Remission rates of peritoneal carcinoma after ip perfusion of a range of chemotherapeutic substances varied from between 15 to 50%. Minimal information is available about adjuvant ip perfusion after operation for cure. Toxicity data are presented from our adjuvant trial using ip perfusion after operation for gastric carcinoma for cure with cisplatin in a randomized fashion. Altogether 59 perfusions were performed, with minimal systemic toxicity, no occurrence of peritonitis and only 1 portal infection. Immunological data show that 1 day after ip perfusion the concentration of natural killer cells is increased in 60% of all perfusions, but decreased only in 28%. We conclude that ip perfusion with cisplatin is a safe procedure with limited toxicity. The efficacy of this technique in peritoneal carcinosis is not yet proven in randomized trials. The observation period of our trial in the adjuvant stage after operation for gastric carcinoma is too short as get to assess the usefulness of the procedure.

Antineoplastic Agents↗
PubMed1987

Free amino acid levels in muscle and liver of a patient with glucagonoma syndrome.

This study set out to measure the amino acid concentrations in the femoral artery, femoral vein, hepatic vein, muscular and hepatic tissue, and urine of a patient with the glucagonoma syndrome. The total plasma amino acid concentration was severely reduced on admission (737 mumol/L, 26% of normal), with only a slight increase during intravenous administration of 200 g of amino acids per day. The total intracellular amino acid levels in the muscle were 86%, and those of the liver were 47% of the normal range. Only 0.62% of the amino acids administered were found in the urine. Arteriovenous amino acid concentration differences across the muscle and splanchnic tissue indicated the release of amino acids (mainly glutamine, glycine, and alanine) from the muscle and the absorption of amino acids by the splanchnic bed. This study shows that the infusion of a high amount of amino acids cannot increase the subnormal plasma AA levels of patients with the glucagonoma syndrome. The low total plasma AA levels are paralleled by decreased intracellular free amino acid levels in the muscle and liver.

Adenoma, Islet Cell↗
PubMed1987

Radioimmunoscintigraphy using monoclonal antibodies before second-look surgery in patients suffering from ovarian cancer.

19 patients with a known history of ovarian cancer were investigated by radioimmunoscintigraphy (RIS) to look for recurrent disease a few days before second-look surgery. The tumor-associated monoclonal antibody HMFG-2 (400 micrograms/patient) was injected intravenously after labeling with radioactive 123I (0.5-2.2 mCi/patient). Scans were reviewed for activity accumulations due to uptake of the tumor-associated antibody by tumor sites. In 15 out of the 19 cases the scan results correlated with the intraoperative findings. There were 2 false-positive and 2 false-negative scans, the latter in patients with subclinical disease. The smallest lesion detected by radioimmunoscintigraphy had a diameter of 1.5 cm. In 3 patients, tumor sites were identified that had been missed by all other routinely performed methods of investigation including transmission computed tomography. These data indicate that RIS is of considerable clinical value in the early detection and localization of recurrent ovarian cancer and may, therefore, improve the management of these patients.

Adult↗
PubMed1986

[Measuring cyclosporin in immunosuppressive treatment following liver and heart transplantation].

Selective suppression of the immune system in graft recipients is now achieved in most cases by treatment with cyclosporine A. Due to large individual differences in absorption, utilization and metabolisation of this drug, therapeutic blood levels (immunosuppression/toxicity) can be maintained only by frequent measurements of the cyclosporine concentrations in blood samples and dosage readjustments. In the present study, we measured cyclosporine in whole blood samples from 37 patients (23 liver and 14 heart transplant recipients) using an high pressure liquid chromatographic method for native cyclosporine A which has been developed in our laboratory and a radioimmunoassay method (cyclosporine A + metabolites). By comparison of the results of HPLC and RIA-measurements (n = 520) we found a relatively stable metabolization rate (RIA/HPLC-ratio) of 4.23 +/- 1.30 for heart transplant recipients. In contrast RIA/HPLC ratios were highly variable in liver graft recipients ranging from 1.3-9 for the same patient in the posttransplant period. The liver recipients could be classified into two groups according to their mean RIA/HPLC-ratios: for 11 patients we observed a mean ratio of 2.65 +/- 0.35, for another 12 patients one of 4.35 +/- 0.75. Lower metabolisation rates seem to be associated with low donor age. No direct correlation was found between changes in RIA/HPLC-ratios and liver function, rejection and infection periods. Rejection treatment with high doses of methylprednisolone had no systematic influence on cyclosporine metabolisation in our patients. Since cyclosporine metabolites, at least those ones which are most abundant, have less immunosuppressive and toxic effects we recommend measurements of cyclosporine blood concentrations with any HPLC-method specific for the unchanged drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗
PubMed1986

Finger systolic pressure: its use in screening for hypertension and monitoring.

A finger sphygmomanometer was compared with a mercury column sphygmomanometer for its ability to screen for hypertension. A total of 881 patients used each machine, both in initial screening and then for monitoring. The finger sphygmomanometer had a specificity of 98.5% in routine screening as compared with 97.6% for the mercury column device. Sensitivity of the finger device was 98.2%. These findings suggest that the finger sphygmomanometer using finger systolic pressure alone is adequate for screening and monitoring blood pressure.

Blood Pressure Determination↗