Search PubMed⌕ Search

Biomedical subjects

L Martin

Publications and source records attributed to L Martin.

At least 415 records · Page 23Linked to original sources

T cell receptor and immunoglobulin gene rearrangement analysis as a laboratory aid in the diagnosis of human malignant lymphoproliferative diseases.

The identification of clonal rearrangements of the immunoglobulin heavy chain and T cell receptor beta chain gene loci by Southern blot analysis has led to advances in the diagnosis and classification of lymphoproliferative disorders. This paper reviews our experience with this technique over a three and a half year period. Specimens from 99 patients with suspected haematological malignancy were tested for leucocyte immunophenotype and immunoglobulin or T cell receptor gene rearrangement. Genotyping provided evidence of clonality in malignancies from 28 patients and demonstrated malignant cell lineage in eight patients not formally deduced from immunophenotyping alone. Our findings suggest that this technique can be employed in conjunction with immunophenotyping to aid in the determination of malignant cell lineage derivation and identification of malignant cell clonality, as well as potentially estimating the extent of disease, detecting relapse, and monitoring disease progression.

Gene Rearrangement↗

Localized epidermal necrolysis (erythema multiforme-like reaction) following intravenous injection of vinblastine.

We report a case of localized epidermal necrolysis that developed 24 hours after an intravenous injection of vinblastine. Clinically, the lesions consisted of erythematous macules, vesicles, and bullae with a linear arrangement over the injected vein. Histologically, the lesions showed features closely resembling erythema multiforme (epidermal necrolysis). We discuss the pathogenesis of this curious cutaneous drug reaction and review the literature concerning local cutaneous complications associated with intravenously administered chemotherapeutic agents.

Erythema Multiforme↗

Modulation of the migrating myoelectric complex by brain noradrenergic systems in rats.

The respective role of central and peripheral noradrenergic systems in the control of migrating myoelectric complex (MMC) was investigated in rats following lesions with 6-hydroxydopamine (6-OHDA). 6-OHDA was injected via intraperitoneal (ip), intracisternal (icis), and intracerebroventricular (icv) routes in rats. Control animals received the vehicle alone. One month later, MMC was recorded in conscious rats chronically fitted with electrodes. The MMC period was significantly lengthened after 6-OHDA ip or icv injection, and slightly shortened after 6-OHDA icis injection. No disruption of central noradrenergic systems was detected after ip lesions. Norepinephrine content was reduced in the digestive tract after ip lesions, in the spinal cord after icis lesions, and in the cortex, the hypothalamus, pons-medulla, and the spinal cord after icv lesions. After icis lesions, noradrenergic perikarya were spared in pons-medulla, whereas only pons noradrenergic perikarya were lesioned after icv lesions. We conclude that lesions of brain noradrenergic systems modify MMC periodicity in rats. The rostral noradrenergic systems may play the major modulatory role.

Animals↗

Influence of biological response modifiers of bacterial origin on disease progression in the MRL-lpr model of systemic lupus erythematosus.

Murine models of systemic lupus erythematosus exhibit some, but not all of the characteristics of human disease. Disease progression in the animal models is related to autoantibodies, genetics, and inflammatory processes. In this report the effects of two bacterial biological response modifiers (BRM) on disease progression in the MRL-lpr model were investigated. The two BRM tested were C. parvum and Bacillus-Calmette-Guerin (BCG), both of which are stimulators of the reticuloendothelial system and both of which have been shown by others to influence disease progression in NZB/W mice. Treatment of 10-week-old mice with C. parvum led to transient alterations in hepatosplenomegaly and plasma proteinase regulation, which then returned to control values. Treatment with BCG led to even more transient effects on the mice. Neither BRM appeared to impact on disease-associated alterations in autoantibody titres, hepatosplenomegaly, or elevations in plasma proteinase activity. Likewise, treatment of 17-week-old MRL-lpr mice with C. parvum did not influence disease progression as evidenced by survival, autoantibody production, or hepatosplenomegaly. Therefore, in contrast to the NZB/W strain, treatment of the MRL-lpr strain with these BRM does not appear to impact on disease progression. This difference may be due to the influence of the lpr accelerator gene in this model.

Aging↗

Loss of pancreatic islet tolerance induced by beta-cell expression of interferon-gamma.

Interferon-gamma (IFN-gamma) is produced during the response to infection and participates in immunostimulatory events. We have previously reported the induction of diabetes in transgenic mice (ins-IFN-gamma) in which the expression of the lymphokine IFN-gamma is directed by the insulin promoter. This diabetes is a result of the progressive destruction of pancreatic islets that occurs with the influx of inflammatory cells. Here we demonstrate that this islet cell loss is mediated by lymphocytes, that engrafted histocompatible islets are destroyed, and that lymphocytes from the transgenic mice are cytotoxic to normal islets in vitro. These results indicate that the pancreatic expression of IFN-gamma can result in a loss of tolerance to normal islets, consistent with its role as an inducer of costimulatory activity, which is essential for lymphocyte activation during an immune response.

Animals↗

Nuclear binding of the estrogen receptor: a potential predictor for hormone response in metastatic breast cancer.

We have previously described an in vitro immunohistochemical test employing anti-receptor antibodies, for demonstrating the nuclear binding characteristics of estrogen receptors (ER) in breast carcinomas. Based on a retrospective analysis of twenty-five patients with estrogen receptor-positive (ER+) breast cancer who were treated with hormone therapy and whose clinical responses were evaluable, we were able to demonstrate that this test may be valuable to predict which, among the ER+ tumors (whether or not they are progesterone receptor positive, PR+), are likely to respond to hormone therapy and which may fail. While tumors in which ER exhibited abnormalities in nuclear binding behavior (ligand-independent nuclear binding or no nuclear binding) failed hormone therapy (16 out of 19 patients), those in which nuclear binding of ER appeared normal (ligand-dependent) in the in vitro test, responded to hormone therapy (5/6 patients). While our previous report dealt with the procedural details, specificity of the reagents, and the design of the study, this report addresses the clinical aspects of this study and response correlation.

Biomarkers, Tumor↗

One-year outcome after therapy with tissue plasminogen activator: report from the Thrombolysis and Angioplasty in Myocardial Infarction trial.

To evaluate the long-term effects of reperfusion with tissue plasminogen activator (t-PA) and an aggressive strategy of revascularization with angioplasty and coronary artery bypass grafting, we obtained 1-year follow-up results from 386 consecutive patients enrolled in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI I) trial. All patients were treated with 100 to 150 mg of t-PA intravenously over 6 to 8 hours, and coronary angiography was performed within 90 minutes of initiation of therapy. In 197 patients with suitable anatomic characteristics, angioplasty was either performed immediately or was deferred for 7 to 10 days on a randomized basis. The remainder of the patients were treated as considered clinically appropriate. The in-hospital mortality rate was 7%, and only 1.9% of patients died in the first year after discharge from the hospital; three patients died of cardiac events and four died of noncardiac causes. Ninety-four percent of patients discharged alive from the hospital remained alive and had no myocardial infarctions during the first 12 posthospital months. Revascularization procedures after discharge from the hospital included angioplasty in 8% of patients and coronary artery bypass grafting in 5%. The high survival rates were evident in high-risk groups defined by age, ejection fraction, and extent of coronary artery disease. At 1-year follow-up 64% of patients less than 65 years of age were employed and only 10% reported that they were disabled; 94% of patients were in Canadian Heart Association class I or II. These low rates of follow-up events suggest a change in the "natural history" of the first year after acute myocardial infarction.

Angioplasty, Balloon, Coronary↗

Effects of a monoclonal antibody against progesterone, on embryo transport, development and implantation in laboratory mice.

A monoclonal antibody against progesterone (11P27) given on Day 2 of pregnancy interrupted pregnancy in BALB/c mice but not in BCF1 mice. The reason for this strain difference remains unclear, although it may involve discrimination by the recipient's immune system. The effects in BALB/c mice were reversed by progestin treatment. A dose of 5 nmol, which completely blocked implantation, had no significant effects on embryo transport and development on Day 4. A dose of 10 nmol did not increase the proportion of abnormal embryos, even though it accelerated tubal transport and increased embryo loss. No tubal retention was evident; most remaining embryos reached the uterus at the normal time. The transformation of morulae to blastocysts was only slightly delayed in 11P27-treated mice, and transfer experiments showed no decrease in embryo viability. The antibody appeared to act by blocking actions of endogenous progesterone on the uterus: uteri of 11P27-treated mice failed to develop a decidual cell reaction to intrauterine oil, and embryos from untreated donors failed to implant in 11P27-treated recipients. Antagonism of progesterone by antibody treatment prevented implantation in BALB/c mice apparently by actions on the uterus rather than on the embryo.

Animals↗

Effects of progesterone antagonists RU486 and ZK98734 on embryo transport, development and implantation in laboratory mice.

Two progesterone antagonists blocked the actions of progesterone on uterine mitosis and epithelial morphology, but had no oestrogenic, anti-oestrogenic, cytotoxic or gestagenic activities in the mouse uterus. They interrupted early pregnancy and were luteolytic. These actions were reversed by treatment with exogenous progestins, but not dexamethasone. Doses of antagonists which blocked pregnancy and were luteolytic induced premature entry of embryos into the uterus on Day 3 and loss from the tract by Day 4. With the more potent RU486, most embryos remaining in the tract on Day 4 were in the oviduct. This 'tube-locking' and accelerated loss were probably due to 'unopposed' actions of ovarian oestrogen. They were reversed by progestin treatment; this suggests that progesterone is essential for normal embryo transport. Doses of antagonists which prevented normal embryo transport and implantation had little effect on preimplantation embryo development. Small increases in numbers of abnormal embryos on Day 4 were not significant or dose dependent. Abnormalities were not correlated with location of embryos, nor prevented by progestin treatment which reversed antagonist effects on embryo transport and implantation. Hence, progesterone is apparently not essential for successful completion of preimplantation development of mouse embryos in vivo.

Animals↗

Purification and Partial Characterization of a Fructanase which Hydrolyzes Natural Polysaccharides from Sugarcane Juice.

A new sugarcane (Saccharum officinarum L.) fructanase which hydrolyzes both high molecular weight polysaccharides mid R:Fructose(4):Galactitol(5)mid R:(n) (SP) and moderate-sized carbohydrates mid R:Fructose(2):Galactitol(3)3mid R:(n) (MMWC) has been purified from sugarcane juice. The K(m) value has been estimated to be 33.7 micrograms per milliliter and 20 micrograms per milliliter for SP and MMWC, respectively. The optimal pH and temperature values are 6.0 and 30 degrees C, respectively. Purified protein has a pl value of 6.35 and a molecular weight of 13.2 kilodaltons. Fructanase activity appears to be Mn(2+)-dependent.

Journal Article↗

Influence of Endogenous Cytokinins on Reverse Mobilization in Cotyledons of Cicer arietinum L: Reproduction of Endogenous Levels of Total Cytokinins, Zeatin, Zeatin Riboside, and Their Corresponding Glucosides.

The embryonic axis plays an essential role in the mobilization of the main reserves of the cotyledons of seeds of Cicer arietinum L. cv Castellana. This control by the axis of the metabolism of the storage products of the cotyledons largely takes place through the cytokinins, which are transported from the embryonic axis to the cotyledons where the mobilization of reserves begins. The principal regulatory role of the endogenous cytokinins concerns the metabolism of carbohydrates and proteins; there is less influence on lipid metabolism. However, each cytokinin seems to have a different role in the mobilization processes. The glucosides, glucosyl zeatin riboside, and glucosyl zeatin act only as storage forms of the hormones. Zeatin riboside affects mainly the mobilization of carbohydrates and has less effect on protein mobilization. Zeatin regulates both the mobilization of carbohydrates and that of proteins and is more marked in the latter case.

Journal Article↗

A nonoxytocinergic prolactin releasing factor and a nondopaminergic prolactin inhibiting factor in bovine neurointermediate lobe extracts: in vitro and in vivo studies.

Several peptidergic PRL-releasing factors (PRFs) have been described; however, none have been proven to be of primary physiological importance in the control of hormone release. Similarly dopamine withdrawal alone cannot completely explain the profiles of PRL secretion observed under a variety of conditions. We describe here the isolation in semipurified form of both a PRF and a PRL-inhibiting factor (PIF) from bovine neurointermediate lobe (NIL) extracts. Acid extracts of bovine NILs stimulated, in a dose-related manner, PRL release from cultured anterior pituitary cells, even after immunoabsorption of endogenous oxytocin from the extract. PIF and PRF activities were semipurified from NIL extracts by Sephadex chromatography and detected by in vitro and in vitro bioassays. The PRF material could be separated from oxytocin by gel sieving and was active in the presence of dopamine in vitro unlike synthetic oxytocin and in cell preparations in which the oxytocin-responsive lactotrophs had been removed by selective cytotoxin cell targeting using an oxytocin-ricin A chain cytotoxic conjugate. The PRF material stimulated PRL secretion in a dose-dependent fashion in conscious male rats after iv injection. The PIF material comigrated on sizing gel chromatography with immunoreactive oxytocin and was active in vitro during dopamine blockade with domperidone and in vivo in the presence of endogenous dopaminergic tone. These data suggest that novel factors present in the NIL might exert physiologically relevant control over lactotroph function and add to the growing literature on the presence of a PRF in the NIL.

Animals↗

Hemodynamic status in critically ill patients with and without acute heart disease.

Physicians have been urged to reduce the use of the pulmonary artery catheter. However, there are no guidelines to help the clinician make the decision to use or withhold invasive monitoring in the individual patient. This study was designed to examine the accuracy of physician estimates of cardiac function in a spectrum of patients with hemodynamic instability to determine whether differences in accuracy among subgroups would suggest subgroups of patients who could be managed without invasive measurements. Physician estimates of cardiac index were found to be sufficiently accurate in patients without acute heart disease that initial management without invasive monitoring may be appropriate in selected cases. However, due to the general inaccuracy of physician estimates, efforts to improve the accuracy of clinical judgments of cardiac function and hemodynamic status should be pursued with vigor in patients both with and without acute cardiac dysfunction.

Aged↗

Ocular manifestation of simian immunodeficiency syndrome (SAIDS).

The management of opportunistic infections is a significant problem in acquired immunodeficiency syndrome (AIDS) and the development of more effective chemotherapeutic agents is needed. We present the ocular manifestations of an AIDS-like disease in rhesus monkeys experimentally infected with simian immunodeficiency virus (SIV) at the Delta Regional Primate Research Center. These findings consisted of rubeosis in the anterior segment and retinitis, optic neuritis, choroiditis and panophthalmitis in the posterior segment of the eye. Investigation of the retinas by electron microscopy revealed SIV in both eyes of one animal and a herpes virus in two animals. Serology confirmed cytomegalovirus (CMV) as the likely agent. This primate model will prove useful for both further investigations of the possible interaction between immunosuppressive lentiviruses and CMV in ocular disease and antiviral drug testing.

Animals↗

The use of serum amylase and lipase in evaluating and managing blunt abdominal trauma.

In order to determine the usefulness of serum amylase and lipase in the initial evaluation and subsequent management of blunt abdominal trauma (BAT) patients, we collected serum amylase and lipase on 85 consecutive BAT patients at admission, hospital day 1, hospital day 3, and hospital day 7. Only one patient had a pancreatic injury. A total of 45 patients (53%) had at least one enzyme abnormality during the study. There was no correlation between amylase or lipase values and age, sex, type of injury, diagnostic tests, operation, and outcome. In a control group of nonabdominal-trauma patients with admit studies only, all enzyme values were normal. We conclude that serum amylase and lipase are randomly elevated in patients with nonpancreatic-BAT both initially and during subsequent hospitalization and are not useful clinical tools in these patients.

Abdominal Injuries↗