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Biomedical subjects

M E Williams

Publications and source records attributed to M E Williams.

At least 163 records · Page 9Linked to original sources

Immunoglobulin and T cell receptor gene rearrangements in human lymphoma and leukemia.

DNA samples from blood leukocytes or tumor biopsies of 45 patients with phenotypic B or T cell neoplasms were analyzed for rearrangements of the immunoglobulin (Ig) or T cell receptor (TCR) genes by Southern blot hybridization analysis. Rearrangements of the Ig heavy chain joining region genes (JH) were present in DNA from each of 28 B cell lymphomas and leukemias; 14 of 21 of these tumors also had rearrangements of the Ig kappa light chain joining (JK) or deleting element (KDel) genes. Conversely, 16 of 17 T cell lymphomas and leukemias had rearranged TCR beta chain genes. One B cell and one T cell tumor had rearrangements of both Ig and TCR genes. There was a strong correlation between the rearrangements of specific genes and the immunophenotype of the tumor: JH rearrangement without TCR beta chain rearrangement occurred only in B cell tumors; TCR beta chain rearrangement with or without JH rearrangement occurred only in T cell tumors, with one exception; and JK and KDel rearrangements were found only in B cell tumors. Thus, rearrangements of the Ig heavy and light chain genes and the TCR beta chain genes were found to be highly sensitive markers of monoclonal human lymphomas and lymphoid leukemias, with the type of gene rearrangements well correlated with the cell lineage of these neoplasms.

Antigens, Neoplasm↗

Role of alpha-adrenergic hormones in potassium homeostasis in the rat.

To determine whether alpha-adrenergic stimulation impairs extrarenal potassium disposal in the rat, we studied the effect of an alpha-agonist and antagonist on the rise in plasma potassium concentration produced by a potassium infusion of 3 mEq KCl/kg over a 90-minute period to nephrectomized rats. Compared with KCl alone, the alpha-agonist phenylephrine caused more than a 25% increment in the peak plasma potassium, and reduced the volume of distribution of the potassium load. Addition of the alpha-blocker, phentolamine, to phenylephrine completely abolished the increment in potassium caused by KCl infusion. There were no differences in plasma bicarbonate, arterial pH, or plasma glucose levels among the groups. When an identical protocol was performed in nephrectomized rats also prepared by adrenalectomy, induction of diabetes, and chemical sympathectomy, the rise in plasma potassium level after KCl infusion was again augmented by phenylephrine. Addition of phentolamine also markedly blunted the increment in potassium in this group. These results show that alpha-adrenergics impair extrarenal potassium disposal in the rat. The effect does not depend on endogenous insulin or other potassium-regulatory factors. alpha-Adrenergics appear to play an important role in extrarenal potassium homeostasis.

Adrenalectomy↗

Outpatient geriatric evaluation.

This article provides a comprehensive description of an established geriatric ambulatory consultation service at Monroe Community Hospital in Rochester, New York. The history of the service is presented and clinic staffing and operations are reviewed. Descriptive information for patients evaluated during a 1-year period and the impact of this team-oriented assessment compared to assessment by physicians are provided.

Aged↗

Rejection of reovirus-treated L1210 leukemia cells by mice.

L1210 leukemia cells were treated in vitro with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and reovirus to determine their interactive effects on rejection of these tumor cells by mice. The cells were treated with BCNU at concentrations of 0, 3, or 10 microM, incubated for 48 h, then treated with reovirus at a multiplicity of infection of 0, 10, 30, or 100 for 2, 6, or 12 h. The survival of mice injected with cells treated with any amount of reovirus, regardless of BCNU treatment, was greater than that of mice injected with untreated cells. Exposure of the cells to reovirus for 6 or 12 h increased the survival of mice injected with these cells as compared with that of mice injected with cells exposed to reovirus for 2 h. Of the survivors, 76% were resistant to subsequent challenge with untreated L1210 cells. These results suggest that activities associated with reovirus replication may cause modifications of L1210 cells that enable them to induce an immune response, thus facilitating their rejection. A lack of correlation between differences in DNA synthesis (measured by 3H-thymidine uptake) by treated cells and the ability of those cells to kill recipient mice indicates that rejection of cells treated with reovirus or BCNU is not due to a decrease in their ability to proliferate or, presumably, to generate lethal tumors. The survival of mice injected with treated L1210 cell preparations containing as few as 2.9% reovirus-infected cells was enhanced to the same degree as that of mice injected with those containing as many as 14.6% infected cells, indicating that modification of only a minor component of the tumor cell population is sufficient to alter the ability of the cells to generate a lethal tumor.

Animals↗

Salsalate kinetics in patients with chronic renal failure undergoing hemodialysis.

A 1500 mg dose of salsalate (SSA) was given to five patients undergoing chronic hemodialysis on an interdialytic day and again before dialysis. Compared with control subjects, patients undergoing dialysis had a lower peak plasma SSA level (17 +/- 3 vs. 45 +/- 2 micrograms/ml; P less than 0.01) that occurred slightly later. In contrast, plasma salicylic acid (SA), the active SSA metabolite, had a similar but later peak level that remained substantially higher. Therefore, the AUC for SA was increased by 50% and the SA t1/2 was prolonged in the patients receiving dialysis (8.1 +/- 0.7 vs 3.8 +/- 0.2 hours; P less than 0.01). During a single treatment, dialysis clearance reduced plasma SA levels, removed 18% of total body SA, and returned the SA t1/2 to nearly normal. Because the elimination of SA is impaired in patients undergoing dialysis, the interdialytic SSA dosage should be reduced. Hemodialysis improves SA kinetics and may be followed by a normal SSA replacement dose. However, periodic monitoring of plasma SA levels is recommended when SSA dosing is begun in patients receiving dialysis.

Administration, Oral↗

Evaluation of older persons in the ambulatory setting.

This report provides a comprehensive description of an established outpatient geriatric consultation service. The basic objectives of the service are to promote health and to prevent or minimize disability. The consultation service uses a multidisciplinary team with core participants from medicine, nursing, and social work and is based in a setting where a wide range of specialty consultants and ancillary services are available. A detailed description of 131 individuals who received geriatric consultations during a one-year period is provided. Despite a substantial burden of disability, most older persons after the consultation process were able to continue living in their own preferred setting. The degree to which the geriatric consultation service contributed to these favorable outcomes is currently being evaluated through a randomized clinical trial.

Activities of Daily Living↗

Calcitriol levels in hypercalcemic patients with adult T-cell lymphoma.

Hypercalcemia is a frequent complication in patients with adult T-cell lymphoma. We measured serum calcitriol (1,25-dihydroxyvitamin D3) levels in five hypercalcemic patients with adult T-cell lymphoma and compared the values with those of five patients with mycosis fungoides, a T-cell neoplasm not associated with hypercalcemia. All five patients with adult T-cell lymphoma had calcitriol levels in or below the normal range. These data show that elevated calcitriol levels are not uniformly elevated in this disorder and may not be the usual cause of hypercalcemia in this subgroup of patients with lymphoma.

Calcitriol↗

Hyperkalemia.

Explore the source record for details and available documents.

Acid-Base Equilibrium↗

A controlled study of ticarcillin plus clavulanic acid versus piperacillin as empiric therapy for fever in the immunocompromised host.

Clavulanic acid, a potent beta-lactamase inhibitor, was studied in fixed combination with ticarcillin and used with tobramycin as empiric therapy for fever in the immunocompromised host. Fifty febrile episodes were evaluated in patients with hematologic malignancy and/or neutropenia. Eighty-one percent of evaluable infections treated with the study regimen of ticarcillin, clavulanic acid, and tobramycin responded. Seventy-four percent of evaluable infections treated with the control regimen of piperacillin, tobramycin, and vancomycin responded (p = 0.4). Resistance to piperacillin and ticarcillin were noted in 23.8 percent of 21 isolated organisms. Resistance to ticarcillin and clavulanic acid was noted in only one (4.7 percent) of the isolated organisms (p = 0.092). Untoward reactions, including rash, nephrotoxicity, and superinfection, were unusual and occurred with equal frequency in the study and control groups. Clavulanic acid in combination with ticarcillin was effective and safe in treating fever in the immunocompromised host.

Bacterial Infections↗

Electronic databases.

Electronic databases corresponding to most of the world's currently published literature and many other types of information are publicly available through online systems. Scientific databases that give references for publications are numerous and widely used; scientific numeric databases that are open to the public are far fewer and less used. Online retrieval systems are becoming easier to use as a result of the introduction of artificial intelligence techniques and user-friendly front ends and gateways. Issues related to electronic databases include public-private sector competition, transborder data flow, copyright, downloading, and the changing roles in database generation and processing.

Bibliographies as Topic↗

Catecholamine modulation of rapid potassium shifts during exercise.

Plasma potassium rises during muscular exercise and falls rapidly when exercise is stopped. Since the sympathoadrenal system is stimulated with exertion and both alpha- and beta-adrenergic agonists affect internal potassium homeostasis, we studied the influence of catecholamines on potassium shifts during and after exercise. Six healthy subjects were given maximal exercise stress tests under three conditions: with no medication (control), during beta-blockade with propranolol, and during alpha-blockade with phentolamine. Compared with a peak rise in plasma potassium of 1.23 +/- 0.27 mmol per liter (mean +/- S.E.M.) during the control study, propranolol caused a rise of 1.89 +/- 0.35 (P less than 0.01) and a sustained elevation during recovery. Phentolamine diminished the rise of potassium (0.70 +/- 0.21 mmol per liter; P less than 0.01) and lowered the potassium level throughout recovery. These effects of catecholamines were independent of the venous pH, the plasma bicarbonate and serum glucose levels, and urinary potassium excretion, and they did not appear to be due to insulin. High norepinephrine and epinephrine levels confirmed the release of catecholamines capable of stimulating alpha- and beta-receptors. Exercise work did not differ among the groups. beta-Adrenergic receptors appear to moderate the acute hyperkalemia of exercise, whereas alpha-adrenergic receptors act to enhance hyperkalemia and may protect against hypokalemia when exertion ceases.

Adrenergic alpha-Antagonists↗

Potentiation of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)-induced cytotoxicity in 9L cells by pretreatment with 6-thioguanine.

9L Rat brain tumor cells were treated with 0.2 microM 6-thioguanine for 48 hr, which produced a 40% cell kill, a small (15%) inhibition of cell growth, and an accumulation of cells in S-phase. Maximum incorporation of [14C]6-thioguanine into cellular DNA occurred after 24 hr of incubation; 70% of the label was incorporated into DNA as 6-thio-2'-deoxyguanosine. Pretreatment of 9L cells for 48 hr with 0.2 microM 6-thioguanine potentiated the cytotoxicity of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) by 50% with a dose enhancement ratio of 1.5, and caused a 30% increase in the number of BCNU-induced sister chromatid exchanges (SCEs) and a 50% increase in DNA crosslinks formed, compared to treatment with BCNU alone. Used as a single agent, 6-thioguanine induced a significant number of SCEs. Results suggest that these effects may be related to the increased formation of DNA crosslinks, possibly as the result of the formation of S6-(2-chloroethyl)-6-thioguanine in cellular DNA.

Animals↗

Extramedullary hematopoiesis. A cause of severe generalized lymphadenopathy in agnogenic myeloid metaplasia.

Although microscopic evidence of extramedullary hematopoiesis in lymph nodes is a frequent finding in autopsy studies of patients with agnogenic myeloid metaplasia, clinically significant lymphadenopathy is a rare occurrence. In this article we describe an unusual case of severe generalized lymphadenopathy and lymphedema secondary to extramedullary hematopoiesis in multiple lymph nodes. With the use of low-dose radiotherapy, both the lymphadenopathy and lymphedema resolved.

Adult↗

The effect of treatment with single and split doses of spirohydantoin mustard on the growth delay of 9L rat brain tumor multicellular spheroids.

The effects of single and split doses of spirohydantoin mustard on the growth delay and cell survival of 9L rat brain tumor multicellular spheroids have been investigated. Treatment with 10-25 microM concentrations of spirohydantoin mustard inhibited the growth of spheroids. Growth delay increased rapidly when assayed during the first 6-10 days after treatment, after which a decrease in delay was observed. Plots of the values for the inflection points from growth curves vs drug concentration were linear, and growth delay correlated well with cell survival. There was less growth delay caused by treating spheroids with two 10 microM concentrations of spirohydantoin mustard than with a single 20 microM concentration. When a 2 or 4 hr time interval was allowed between treatment with 10 microM concentrations of spirohydantoin mustard the delay observed was greater than that obtained with the split dose control. When the resolution of the growth delay assay is considered, the split dose effect can be explained by the existence of a 5 microM threshold before any growth delay is observed. Nonetheless, the finding that spheroids treated on the split dose protocol recover from drug damage may have implications for the design of clinical protocols.

Animals↗

Phagocytic cells synthesize 19-nor-10-keto-25-hydroxyvitamin D3, a metabolite that may induce differentiation of the human monoblastic cell line U937.

Phagocytic cells, including normal human blood neutrophils and monocytes, metabolize 25-hydroxyvitamin D3 in vitro to more polar metabolites. Cells of the human monoblastic cell line U937 produced three metabolites when incubated with 25-hydroxyvitamin D3. One of these metabolites, previously designated peak III, has its maximal absorbance at 310 nm. Mass spectral analysis of the trimethylsilylated derivatives of peak III revealed a spectral pattern very similar to that published for the trimethylsilylated derivatives of 19-nor-10-keto-25-hydroxyvitamin D3. The biosynthetic 19-nor-10-keto-25-hydroxyvitamin D3 was active in the induction of differentiation of U937 cells.

Calcifediol↗

Positive direct antiglobulin tests due to clavulanic acid.

Clavulanic acid, a beta-lactamase inhibitor, was found to be associated with the development of a positive direct antiglobulin test. Of 23 antibiotic courses in patients treated with ticarcillin, clavulanic acid, and tobramycin, 10 (43.5%) developed positive direct antiglobulin tests versus 2 of 26 (7.7%) patients treated with piperacillin and tobramycin (P = 0.0044). In vitro immunohematological studies showed that clavulanic acid caused a nonimmunologic adsorption of plasma proteins onto the erythrocyte surface. Hemolysis was not associated with such nonimmunologic adsorption. However, the resulting positive antiglobulin test might delay cross matching of blood products for transfusions or interfere with the evaluation of true immune-mediated hemolytic anemia.

Clavulanic Acid↗