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Biomedical subjects

M A Lynch

Publications and source records attributed to M A Lynch.

At least 91 records · Page 5Linked to original sources
PubMed1991

A heparin-like anticoagulant as part of global abnormalities of plasma glycosaminoglycans in a patient with transitional cell carcinoma.

A patient is described in whom a circulating heparin-like anticoagulant developed during the terminal course of metastatic transitional cell carcinoma. The anticoagulant, which was identified as heparan sulfate, was the clinical sign of global abnormalities in the patient's plasma glycosaminoglycans. Subsequent analysis disclosed increased amounts of chondroitin sulfate as well as heparan sulfate. In addition, the charge density and molecular weight of the patient glycosaminoglycans and their organization into proteoglycans differed significantly from glycosaminoglycans isolated from normal plasma samples.

Aged↗
PubMed1990

Increases in glutamate release and phosphoinositide metabolism associated with long-term potentiation and classical conditioning.

Long-term potentiation (LTP) is a widely studied model of the kind of activity-dependent modulation of synaptic efficacy which is assumed to provide the physical basis for learning. Whether LTP, in the hippocampus or elsewhere in the brain, does in fact serve such a role is still a matter for debate. One approach to answering this question is to identify physiological or biochemical changes which are common to both learning and LTP; in the hippocampus, for example, one can ask whether the biochemical changes associated with LTP are also associated with learning. In this chapter we summarize the results which we have obtained in a study of glutamate release and phosphoinositide turnover in the dentate gyrus of rats trained in a classical conditioning task. The similarity between the changes occurring after classical conditioning and those associated with LTP is consistent with the hypothesis that LTP is one of the mechanisms by which a neural trace of the learned association is formed. We discuss this interpretation in the light of the observation that classical conditioning does not appear to affect synaptic responses in the hippocampus.

Animals↗
PubMed1990

Arachidonic acid increases inositol phospholipid metabolism and glutamate release in synaptosomes prepared from hippocampal tissue.

We have been interested in the possibility that arachidonic acid or one of its 12-lipoxygenase metabolites may function as a retrograde messenger in long-term potentiation (LTP) in the dentate gyrus of the hippocampus. One criterion required of a retrograde messenger is that it stimulates presynaptic changes. Here, two possible presynaptic actions of arachidonic acid and its 12-lipoxygenase metabolites, 12-hydroxyeicosatetraenoic acid (HETE) and 12-hydroperoxyeicosatetraenoic acid (HPETE), are examined. We report that arachidonic acid, HETE, and HPETE significantly increase both K(+)-stimulated release of [3H]glutamate and [3H]inositol labelling of inositol phosphates in synaptosomes, whereas other biologically important fatty acids (oleic, palmitic, and stearic) failed to induce a similar response. The findings of these experiments are consistent with the hypothesis that arachidonic acid, HETE, or HPETE may play the role of a retrograde messenger in LTP.

Animals↗
PubMed1990

Arthroscopic meniscal repair using an exogenous fibrin clot.

In this series of 153 meniscus tears, 8% were isolated whereas 92% were in conjunction with anterior cruciate ligament (ACL) tears. Exogenous fibrin clot was injected with a blunt needle in the seam of the tear. One to 2 ml of clot was sufficient to fill an average defect. When gaps could not be closed, such as with a radial split or flap in the posterior one-third of the meniscus, a fascia sheath was used to cover these defects and the exogenous clot was injected under the cover of the sheath. ACL-deficient knees were stabilized with an intraarticular reconstruction. Overall results were 64% healed, 24% incompletely healed, and 12% failed (less than 50% of vertical height of tear healed). In ACL-associated knees, the failure rate was 1.5% for tears in which surgery occurred up to two months after the time of injury. The failure rate for tears surgically treated two months to several years after injury was 20%. Complex tears had an even higher failure rate of 22%. It is these tears that will be treated with the fascia sheath. The isolated tear failure rate was 41% without the exogenous fibrin clot versus 8% with the exogenous clot. Complications included retear and popliteal neurovascular injury. Repair of almost all menisci in young active athletes is possible using the transarticular arthroscopic technique with a posterior incision. Repairs of tears of less than two months' duration from the time of injury to surgery result in significantly higher healing rates than those of more chronic tears. Isolated repairs heal significantly better with exogenous fibrin clot injection.

Adolescent↗
PubMed1989

Effect of duration of exposure to verapamil on vincristine activity against multidrug-resistant human leukemic cell lines.

Verapamil sensitizes multidrug-resistant cell lines to various heterocyclic anticancer drugs by inhibition of energy-dependent release of drug, presumably by interaction with membrane glycoproteins involved in drug efflux. This work assessed verapamil sensitization of human multidrug-resistant lymphocytic and myeloid leukemic cell lines (CEM/VLB100, HL-60/AR) to vincristine during exposures of short duration (4 h). When cells were transferred to drug-free medium immediately after simultaneous 4-h exposures to vincristine and verapamil, the antiproliferative activity of vincristine was not altered in CEM/VLB100 cells and was only moderately increased in HL-60/AR cells. In contrast, when cells were transferred to verapamil-containing medium, vincristine activity was greatly increased against both CEM/VLB100 and HL-60/AR cells. Verapamil enhanced accumulation and inhibited release of [3H]vincristine by CEM/VLB100 and HL-60/AR cells, indicating that the sensitization was due to an increase in cell-associated vincristine after transfer of cells to vincristine-free medium. Slot blot analysis of cellular RNA with the pMDR1 probe revealed high levels of expression of the mdr1 gene in CEM/VLB100 cells but no detectable expression in HL-60/AR cells. Consistent with this finding, polypeptides (Mr 170,000 to 180,000) that were recognized by a monoclonal antibody (C219) against P-glycoprotein were greatly overexpressed in CEM/VLB100 cells, but were expressed at low levels, if at all, in HL-60/AR cells. These results demonstrate the importance of duration of exposure to verapamil in reversing multidrug resistance, not only in cells that overexpress P-glycoprotein but also in cells, such as HL-60/AR, that express little, if any, P-glycoprotein.

Cell Division↗
PubMed1989

Arachidonic acid induces a long-term activity-dependent enhancement of synaptic transmission in the hippocampus.

Long-term potentiation (LTP) is a widely studied model of the synaptic basis of information storage in the mammalian brain. The induction of LTP is triggered by the postsynaptic entry of calcium through the channel associated with the N-methyl-D-aspartate (NMDA) receptor, whereas its maintenance is mediated, at least in part, by presynaptic mechanisms. To explain how postsynaptic events can lead to an increase in transmitter release, we have postulated the existence of a retrograde messenger to carry information from the postsynaptic side of the synapse to recently active presynaptic terminals. Candidates for a retrograde messenger include arachidonic acid or one of its lipoxygenase metabolites. Here we report that weak activation of the perforant path, when given in the presence of arachidonic acid, leads to a slow-onset persistent increase in synaptic efficacy both in vivo and in vitro. The activity-dependent potentiation thus produced is accompanied by an increase in the release of glutamate, and is non-additive with tetanus-induced LTP. These observations indicate a role for arachidonic acid as a retrograde messenger in the later, but not the initial, stages of LTP.

2-Amino-5-phosphonovalerate↗
PubMed1989

The increase in [3H]glutamate release associated with long-term potentiation in the dentate gyrus is blocked by commissural stimulation.

Previous findings have indicated that long-term potentiation (LTP) in the perforant path-granule cell synapses is accompanied by an increase in K+-stimulated, calcium-dependent release of [3H]glutamate 45 min after the induction of LTP. Here we report that release of [3H]glutamate is increased at 3 time intervals following induction of LTP, 2.5 min, 45 min and 3 h. Stimulation of the commissural input to the granule cells blocks the induction of LTP and the increase in [3H]glutamate release.

Animals↗
PubMed1989

Nordihydroguaiaretic acid blocks the synaptic component of long-term potentiation and the associated increases in release of glutamate and arachidonate: an in vivo study in the dentate gyrus of the rat.

The dentate gyrus of anaesthetized rats was perfused with artificial cerebrospinal fluid while field responses evoked by stimulation of the perforant path were monitored. Perfusates were collected for analysis of endogenous glutamate, aspartate and arachidonate. In animals in which long-term potentiation was induced by tetanic stimulation, there was a sustained increase in the concentration of glutamate in the perfusate, and, less reliably, in aspartate, as previously reported by Bliss et al. (J. Physiol., Lond. 377, 391-408, 1986) and Errington et al. (Neuroscience 20, 279-284, 1987). The lipoxygenase and phospholipase A2 inhibitor nordihydroguaiaretic acid, when added to the perfusate 30 min before the tetanus, abolished both long-term potentiation of the population excitatory postsynaptic potential and the tetanus-induced increase in glutamate release. Long-term potentiation of the population spike was reduced but not abolished. There was also a sustained increase in the release of arachidonic acid following the induction of long-term potentiation which did not occur when induction was blocked by nordihydroguaiaretic acid. These results are discussed in the light of the possibility that arachidonic acid or one of its lipoxygenase metabolites may be the retrograde messenger which we have postulated is released from postsynaptic sites following tetanic stimulation to trigger increased transmitter release from presynaptic terminals.

Action Potentials↗
PubMed1989

Glucocorticoid inhibition of Na-SO4 transport by chick renal brush-border membranes.

To examine the effect of glucocorticoids on sulfate transport by the chick (domestic Gallus gallus) renal tubule we dosed 3-wk-old animals with 60 micrograms dexamethasone/100 g body wt at 24 and 6 h before isolation of renal brush-border (BBM) and basolateral membranes (BLM). Dexamethasone treatment significantly reduced Na-dependent sulfate transport by BBM and had no effect in paired membranes on bicarbonate, proton, or electrical gradient-driven sulfate transport. The glucocorticoid treatment had no statistically significant effect on HCO3-SO4 exchange in the BLM. Kinetic analysis of the dexamethasone effect on the Na-SO4 transport process showed that apparent Vmax was significantly decreased to almost one-half that seen in controls (from 676 to 348 pmol.mg protein-1.5 s-1). The Km in control BBM was 0.40 +/- 0.095 mM and was not significantly different in dexamethasone-treated membranes (0.53 +/- 0.094 mM). To determine whether the dexamethasone-induced decrease in Na-SO4 transport by BBM was indirectly caused by stimulation of Na-H exchange and more rapid dissipation of the initial Na gradient used to drive sulfate uptake, we examined the effect of 0.1 mM amiloride on Na-SO4 uptake by BBM. With amiloride present, dexamethasone treatment caused Vmax to significantly drop from 1,102 to 660 pmol.mg protein-1.5 s-1. Amiloride had no statistically significant effect on the Km. The extent to which amiloride increased Na-SO4 transport and blocked 22Na uptake by BBM did not appear to be related to hormone treatment. The data indicate that glucocorticoids may participate in the regulation of sulfate excretion.

Alkaline Phosphatase↗
PubMed1988

Increased hydrolysis of phosphatidylinositol-4,5-bisphosphate in long-term potentiation.

Inositol phospholipid hydrolysis was examined in slices and synaptosomes prepared from area CA3 of control hippocampi and hippocampi in which long-term potentiation (LTP) was induced in vivo. In both synaptosomes and slices, LTP was associated with an increase in [3H]inositol labelling of inositol phosphates but not phosphoinositides. Glutamate (10(-3) M) significantly increased labelling of inositol phosphates in slices obtained from control tissue but had no effect either in slices obtained from potentiated tissue or in synaptosomes obtained from control or potentiated tissue. The finding that glutamate had no significant effect in slices prepared from potentiated tissue suggests that glutamate-mediated stimulation of inositol phospholipid hydrolysis in a postsynaptic compartment may be saturated in LTP. The possibility that the increase in phospholipid hydrolysis associated with LTP which we report here may be linked with the previously reported increase in transmitter release is discussed.

Animals↗
PubMed1988

Determination of immune status to measles, rubella, and varicella-zoster viruses among medical students: assessment of historical information.

We examined the serological susceptibility of entering medical students to measles, rubella, and varicella-zoster (VZV) viruses over a four-year period. Serological results were then compared to historical information to ascertain whether undocumented histories of disease or vaccination could be used to identify students who may not need serological testing. For measles, historical information was of no benefit in predicting immunity. For VZV and, to a greater extent, rubella, a higher seropositive rate was seen in students claiming a positive history.

Antibodies, Viral↗
PubMed1988

CT of peritoneal lymphomatosis.

The CT and clinical findings are presented in seven patients with diffuse peritoneal malignancy caused by non-Hodgkin lymphoma. All seven patients had CT evidence of ascites, omental infiltration, and peritoneal implants mimicking carcinomatosis. Bulky retroperitoneal or mesenteric adenopathy was present in only one patient. Four of the seven patients had documented AIDS. Paracentesis provided a diagnosis of lymphoma in only one of the seven patients. In the other six patients, the final diagnosis was established by surgery (three patients), by autopsy (one patient), by laparoscopy (one patient), and by guided needle aspiration (one patient). Although uncommon, lymphoma should be considered in patients who have diffuse peritoneal malignancy, particularly those who are at risk for AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Lesions of the head and neck in patients with AIDS: CT and MR findings.

The CT and/or MR findings were reviewed in 43 patients with head and neck disease; 27 had AIDS, 14 had AIDS-related complex, and two had positive human immunodeficiency virus serologies. Fourteen patients had infections, 15 had tumors, and 15 had benign lymphoid hyperplasia. Deep cervical infections were caused by bacterial and mycobacterial organisms, including Mycobacterium avium-intracellulare. Bacterial infections were clinically more virulent than they would be in immunocompetent patients. Neoplasms included Kaposi sarcoma, lymphoma, and squamous cell carcinoma. Benign lymphoid hyperplasia demonstrated enlargement of the cervical lymph nodes, adenoids, and tonsils. Although there was considerable overlap in the imaging characteristics of the various diseases seen, several distinguishing features were noted. Cellulitis, with infiltration and thickening of the subcutaneous fat, was typical of bacterial infections, but was uncommon with tumors or mycobacterial infections. Lymph nodes with necrotic centers were seen with Kaposi sarcoma, squamous cell carcinoma, and mycobacterial infection, but not with lymphoma or benign lymphoid hyperplasia. Benign adenoidal enlargement is usually symmetric with a flat anterior border, but bulky lesions indistinguishable from tumor were seen in two patients. It is important for radiologists to be aware of the spectrum of head and neck disease in patients with human immunodeficiency virus. The CT and MR assessment can guide biopsy and assist in planning therapy.

AIDS-Related Complex↗
PubMed1988

Arthroscopic meniscus repair with a posterior incision.

The transarticular arthroscopic approach with a posterior incision provided a method of repairing more than 98% of unstable meniscus tears encountered between November 1983 and November 1986. A clinically stable bond was obtained in most of these tears with a subjective failure rate of 2% or less. There was a trend towards better healing of isolated meniscus repairs and lateral meniscus tears less than eight weeks old associated with ACL reconstruction when a blood clot injection was used to supplement the rasp abrasion of the parameniscal synovium. Healing of rim widths to 5 mm can be obtained with these methods. Indications for meniscus repair include all lateral meniscus tears and all medial meniscus tears except when repair of a stump would not replace 25% or more of the missing area. In our experience, this includes more than 98% of all unstable meniscus tears. Contraindications to meniscus repair include short (10 mm or less) stable tears, partial thickness (less than 50% of vertical height), and shallow radial tears (3 mm or less in depth). The posterior incision and popliteal retractor are necessary to protect the popliteal neurovascular structures.

Adolescent↗