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Biomedical subjects

L Lai

Publications and source records attributed to L Lai.

At least 91 records · Page 5Linked to original sources
PubMed1992

Among naive precursor cell subpopulations only progenitors of memory B cells originate germinal centers.

Immunization leads to the generation of both antibody-forming cells (AFC) and memory B cells which are thought to arise in germinal centers within lymphoid follicles. The findings that the precursors to memory B cells reside in the J11Dlo subpopulation of the spleens in non-immune mice and that this subpopulation is distinct from conventional AFC precursors, including CD5+ B cells, suggest that the precursors of germinal centers might also reside in the J11Dlo subpopulation. To test this hypothesis, SCID mice were repopulated with CD4+ carrier-primed T cells and T-depleted J11Dlo, J11Dhi or CD5+ B cells and immunized with a hapten-carrier conjugate. Only the J11Dlo population was enriched for cells that produced germinal centers. Thus, the subpopulation of precursors that generates memory B cells also originates germinal centers.

Animals↗
PubMed1992

Plasmin generation induces neutrophil aggregation: dependence on the catalytic and lysine binding sites.

We established that plasmin (10(-10) M to 10(-6) M) caused neutrophils (PMN) to aggregate using an in vitro assay. Plasminogen had no PMN aggregatory activity even at a concentration of 2 microM. However, plasminogen caused PMN to aggregate when incubated with plasminogen activators [tissue plasminogen activator (25-200 U/ml) or urokinase (5-500 U/ml)]. Tissue plasminogen activator and urokinase alone had no PMN aggregatory activity. Analysis of these incubation mixtures indicated that plasmin was generated in the process and that the time course of plasmin generation correlated with the aggregation response. Active-site-inhibited plasmin did not induce PMN aggregation, indicating that a functional catalytic site was required for the response. Pretreatment of PMN with either active-site-inhibited plasmin or tranexamic acid prevented PMN aggregation by plasmin, indicating that both binding of plasmin to the cell surface via the lysine binding sites and catalysis were required for the response. The generation of plasmin during activation of fibrinolysis may play a pro-inflammatory role by mediating aggregation of PMN.

Binding Sites↗
PubMed1992

Building protein backbones from C alpha coordinates.

An automatic procedure for building polyalanine backbones from guiding alpha-carbon positions is presented. Polyalanine backbones are built based on the geometric restraints of angle N-C alpha-C and the knowledge of main-chain dihedral angle distributions. A building module constructs a list of polyalanine backbones that follow exactly the C alpha trace. Then a selection module selects one backbone with the largest portion of phi-psi pairs in favoured regions. Several test cases on C alpha coordinates from X-ray refined structures give acceptable results. Less than 10% of the peptide planes are incorrectly built, and the result is not sensitive to random shift up to 0.5 A of C alpha coordinates.

Amino Acid Sequence↗
PubMed1992

Culturally competent occupational therapy in a diversely populated mental health setting.

Cultural sensitivity is a crucial component of health care provision, particularly in psychiatric settings. As society becomes more multicultural, it is essential for occupational therapists to continue to develop cultural competence, which is defined in this paper as an awareness of, sensitivity to, and knowledge of the meaning of culture. At San Francisco General Hospital, an innovative multicultural model consisting of special focus programs is used. The key to the success of such programs is a culturally competent professional staff.

Clinical Competence↗
PubMed1992

[Radioimmunoassay of serum and CSF myelin basic protein and its application to patients with acute cerebrovascular accident].

Myelin basic protein (MBP) was measured in the serum and CSF of patients with acute cerebrovascular disease (CVD, 34 cases), demyelinating disorders (DMD, 30 cases) and other neurological diseases (OND, 26 cases) by using a double antibody radioimmunoassay (RIA). Patients with acute CVD had a mean serum MBP concentration and positivity rate much higher than those with DMD and OND. The differences were significant (P < 0.05). In CSF, MBP levels in patients with acute CVD and patients with DMD were significantly greater than those in OND patients (P < 0.05). The results also show that there was a linear relationship between the CSF MBP levels and the serum MBP levels in patients with acute CVD (r = 0.72, P < 0.01), but no such relationship in patients with DMD and OND. The amount of serum MBP was also significantly correlated to the severity of acute CVD, to the level of consciousness disorder and limb paralysis, and to the extent and site of the cerebral lesion at CT-scan (P < 0.05). This study shows that the measurement of brain specific MBP in serum as a marker of cerebral damage may have clinical value in the diagnosis and prognosis of patients with CVD.

Cerebral Hemorrhage↗
PubMed1992

[A study on the location of immuno-suppressive factor(s) in restraint rats and mice].

A serum lymphocyte-proliferation suppressive factor(s) induced by restraint stress over 10 h was found in previous studies in both rats and mice. The present study was undertaken to investigate the sites of its production. The results show that large doses of irradiation and cyclophosphamide (CY) decreased the total number of splenic nucleated cells, but the production of the suppressive factor was inhibited only by irradiation. This indicates that the drop in total number of lymphocytes does not play any key role in the production of the serum suppressive factor. Cell classification showed that the ratio of T to B cell was decreased by radiation but increased by CY, suggesting that this ratio may be relevant to the production of the factor. Inhibition of the production was also observed in nude mouse (an animal showing a lack of T cell activity), again supporting that T cells are involved in the production of the inhibitory factor.

Animals↗
PubMed1992

[Nicardipine attenuates the sympathetic reflex of orthostatism: do dihydropyridine-sensitive calcium channels regulate noradrenaline release?].

Twelve hypertensive subjects were treated for 2 weeks with the dihydropyridine calcium channel antagonist nicardipine (40 mg daily) according to a double-blind, placebo-controlled study protocol. Nicardipine treatment significantly decreased systolic and diastolic blood pressure and increased plasma noradrenaline levels measured at supine rest. However, the treatment significantly inhibited the physiological increase of circulating neurotransmitter following sympathetic stimulation induced by orthostatism. These results suggest that dihydropyridine-sensitive calcium channels may modulate the noradrenaline release from nerve terminals of the peripheral sympathetic nervous system.

Adult↗
PubMed1991

Thrombin-mediated release of lipids from pulmonary artery endothelial cells promotes neutrophil adherence.

We previously have described the ability of alpha-thrombin (the native procoagulant enzyme) to stimulate adherence of neutrophils to pulmonary artery endothelial cells. In the present study, we observed that conditioned medium factors released by alpha-thrombin (10(-8) M) treatment of cultured ovine pulmonary artery endothelial cells increased neutrophil adherence to naive pulmonary artery endothelial monolayers. This effect was independent of any residual alpha-thrombin present in the medium. In contrast to thrombin-induced neutrophil adherence, adherence of neutrophils mediated by the conditioned medium was not inhibited by the anti-CD18 monoclonal antibody 60.3, indicating a CD18-independent mechanism. The factors generated by the action of alpha-thrombin on endothelial cells also resulted in concentration-dependent neutrophil migration. The neutrophil adherence- and migration-promoting activities were isolated in the ether portion after extraction of the conditioned medium. Chromatographic analysis showed that the active components (which resolved into two peaks by reversed-phase high-performance liquid chromatography) were relatively hydrophilic low molecular weight lipids without phosphorus or amino acids. Reconstitution of these peaks indicated that they mediated neutrophil adhesion and migration responses. The results indicate that lipid factors promoting neutrophil adhesion and migration are generated by the action of thrombin on pulmonary artery endothelial cells. The generation of these factors may contribute to the amplification of the lung inflammatory response after pulmonary intravascular coagulation induced by thrombin.

Amino Acids↗
PubMed1991

[Radioimmunoassay of serum myelin basic protein].

Using purified human brain myelin basic protein (MBP) to raise antiserum in rabbits and to prepare 125I-labelled MBP (chloramine-T method), We have established a high specific, precise and sensitive double-antibody radioimmunoassay for the measurement of human serum MBP. The sensitivity was 0.5 ng/ml. In the present study, the serum samples of thirty patients with various neurological diseases were detected. An important clinical implication is that serum MBP level should serve as an index for the damage degree of central neurological diseases.

Animals↗
PubMed1990

Tumor necrosis factor enhances the neutrophil-dependent increase in endothelial permeability.

We examined the effect of tumor necrosis factor alpha (TNF alpha) on the increase in pulmonary microvascular endothelial monolayer permeability induced by activated neutrophils (PMN). Layering of PMN onto endothelial monolayers followed by activation of PMN with phorbol 12-myristate 13-acetate (PMA) increased 125I-albumin clearance rate across the monolayers. Pretreatment of endothelial monolayers for 6 hr with TNF alpha (200 U/ml) potentiated the PMN-dependent increase in endothelial permeability, whereas 1 hr or 6 hr pretreatment of endothelial monolayers with 200 U/ml and 100 U/ml, respectively, TNF alpha did not enhance the response. Adherence of PMN to the endothelial cells was increased at 1 and 6 hr after TNF alpha (200 U/ml) treatment, but the adherence response was markedly greater following 6 hr of TNF alpha. The TNF alpha treatment of endothelial cells did not enhance neutrophil activation responses to PMA. Pretreatment of PMN with IB4, a MAb to the CD18 integrin, the common beta subunit of the adhesion proteins LFA-1, Mac-1, and p150,95 of PMN, reduced the increases in PMN adherence and the endothelial monolayer permeability induced by the 6 hr TNF alpha treatment. In contrast, pretreatment of PMN with OKM-1, a MAb to the CD11b epitope (alpha-subunit), had no effect on the adherence and the potentiation of the increase in permeability. The potentiation of the PMN-dependent permeability increase and enhanced endothelial adhesivity at 6 hr after TNF alpha priming of endothelial cells was dependent on protein synthesis. The results indicate that protein synthesis-dependent expression of an endothelial ligand for CD18 and resultant endothelial hyperadhesiveness potentiates the PMN-mediated increase in endothelial permeability after TNF alpha activation of endothelial cells. The priming of endothelial cells by TNF alpha may be a critical step in the mediation of endothelial injury.

Animals↗
PubMed1990

Different patterns of left ventricular filling in arterial hypertension.

To determine whether left ventricular (LV) filling dynamics may be influenced by the type of LV morphological adaptation to arterial hypertension, pulsed Doppler mitral flow velocity recordings were performed in 30 hypertensive patients and in 18 normotensive subjects matched for age, body surface and heart rate. Peak early (E) and late (A) mitral flow velocity, A/E ratio (A/E), time to peak E (TP), acceleration (AHT) and deceleration half-time (DHT) of early mitral flow and isovolumic relaxation time (IRT) were measured. Compared with the control group, hypertensive patients showed prolonged IRT and DHT, increased A and A/E, whereas TP, AHT and E were unchanged. Hypertensive patients were classified into two subgroups on the basis of h/r ratio (h/r). Subgroup 1: 16 patients with normal h/r, less than 0.42, (five patients with increased LV mass index, greater than 129.2 g m-2, and 11 patients with normal LV mass index, less than 129.2 g m-2). Subgroup 2: 14 patients with increased h/r, greater than 0.42, (nine patients with increased LV mass index, greater than 129.2 g m-2 and five patients with normal LV mass index, less than 129.2 g m-2). In Subgroup 1 the cardiac output (CO) was increased and the total peripheral resistance (TPR) was unchanged in comparison with the control group. In Subgroup 2 the opposite haemodynamic profile was detected: normal CO and increased TPR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

[Isolation and purification of myelin basic protein from human brain].

A simplified procedure for isolation and purification of myelin basic protein (MBP) from human brain is described. Purified myelin from white matter was isolated at first, then delipidated with heated organic solvents. The pellet was washed with triethanolamine buffer and extracted with 0.01 mol/L HCl. Finally the protein in the acidic supernatant was purified with Sephadex G-150 column. By using three different PAGE and immunoelectrophoresis, the purified MBP was identified as a homogeneous component with an apparent molecular weight of 18.5 kd and pI 10.6. This procedure has the advantage of simplicity, rapidity, high yield and purity.

Adult↗
PubMed1989

Role of catalytic and lysine-binding sites in plasmin-induced neutrophil adherence to endothelium.

Plasmin resulted in increased neutrophil adherence to cultured ovine pulmonary artery endothelial cell monolayers in a concentration-dependent manner (10(-12)-10(-7) M). The adherence response increased fivefold above baseline within 60 min after addition of plasmin (10(-8) M) and the response persisted up to 30 min after removal of plasmin. The neutrophil adherence was mediated by the action of plasmin on neutrophils rather than endothelial cells. The response was the result of an increase in functional activity of CD18 neutrophil cell surface adhesive glycoprotein. Neutrophil adherence was inhibited by pretreatment of neutrophils with MAbs IB4 and 60.3 targeted against the beta chain of the CD18, whereas control isotypic MAb 60.5 against HLA class I antigen had no effect. The plasmin catalytic site was not involved in the response. Lys-plasminogen had reduced adherence-promoting activity relative to plasmin, whereas glu-plasminogen had no effect. Elastase-derived plasminogen fragments corresponding to kringle 1+2+3 and kringle 4 (both of which contained the lysine-binding sites) possessed neutrophil adherence-promoting activities similar to plasmin, whereas miniplasminogen (which contains the catalytic site but no lysine-binding sites) had minimal effect, indicating the involvement of lysine-binding sites in the response. Blocking lysine-binding sites of plasmin and elastase-derived plasminogen fragments with tranexamic acid (IC50 of 5 mM) inhibited neutrophil adherence. A monospecific polyclonal antibody against the lysine-binding sites also reduced the neutrophil adherence-promoting activity of plasmin. The results indicate that plasmin induces neutrophil adherence to the endothelium and that the effect is mediated by lysine-binding sites on plasmin.

Animals↗
PubMed1989

Work stress and mental distress.

In a study of 14 managers and 25 workers who were referred for psychiatric treatment, the majority suffered from depressive illness (60%) or anxiety neurosis (28%). The main work problem of the managers was conflict with the employers (or directors), but for the workers the main problem was difficulty with fellow workers. The patients' scores on the Work Environment Scale (WES) indicated that the managers felt they had little supervisor support and work pressure was great. However the workers complained of poor peer cohesion but could get on well with the employers, and their work was not too taxing.

Adolescent↗
PubMed1988

Des-acetyl-alpha-MSH and not alpha-MSH is the major form of alpha-MSH in amniotic fluid.

Immunoreactive alpha-melanocyte stimulating hormone (IR-alpha-MSH)-like activity was measured by radioimmunoassay (RIA) in at term pregnancy amniotic fluid prior and after adsorption on a Sep-pak C18 cartridge. alpha-MSH activity was 3-4 times lower after Sep-pak purification but, unlike the levels of IR-alpha-MSH in the fluid analyzed in toto, increased linearly with the volume of fluid analyzed. Furthermore, fractionation by high pressure liquid chromatography (HPLC) revealed that IR-alpha-MSH recovered from the Sep-pak was due to several peptides rather than to a single peptide. The most abundant of them (50% of total activity) behaved like authentic des-acetyl-alpha-MSH. Since des-acetyl-alpha-MSH is also the most abundant alpha-MSH-like peptide in the fetal pituitary gland, the present results suggest that the fetal pituitary is a main source of des-acetyl-alpha-MSH in the amniotic fluid.

Amniotic Fluid↗
PubMed1988

Thrombin-induced generation of neutrophil activating factors in blood.

The authors examined the in vitro effects of serum generated by the action of alpha-thrombin on citrated whole blood or plasma. Serum samples were assessed for their ability to induce neutrophil aggregation, neutrophil adherence to cultured endothelial cell monolayer, and superoxide anion generation. The results indicated that both blood- and plasma-derived sera induced similar increases in neutrophil aggregation. Both sera also induced neutrophil adherence to cultured bovine pulmonary artery endothelial monolayer. The adherence increased in a time-dependent manner, producing little change after 5 minutes, and reached maximal response at 60 minutes. Full potency of the neutrophil adherence was evident with serum samples obtained after clotting time of 20 minutes but not at 5 minutes clotting time. The adherence-inducing activity of serum was gradually lost after storage at -20 C and was abolished by 100 C treatment for 2 minutes. In contrast, heating serum to 56 C for 30 minutes did not alter the adherence-inducing activity. Both ether and aqueous fractions obtained after ether extraction of serum possessed adherence-promoting activities, indicating that multiple factors (both lipid and water soluble) were involved. Pretreatment of the endothelium with serum resulted in increased endothelial adhesiveness, but the serum pretreatment failed to induce adhesiveness to subendothelial matrix, indicating that endothelial cells play an active role in acquiring the adhesive property. Serum obtained from thrombin-generated whole blood also resulted in a modest degree of neutrophil superoxide anion generation, but this did not occur with plasma-derived serum. The results indicate that serum factors obtained by clotting blood with thrombin induce neutrophil aggregation and neutrophil adherence to the endothelium as well as superoxide production. These factors appear to be generated in the plasma phase, because the responses were similar in blood- and plasma-derived serum.

Animals↗
PubMed1987

Thrombin-induced thromboxane generation by neutrophils and lymphocytes: dependence on enzymic site.

We examined the effects of thrombin on thromboxane generation by sheep neutrophils and lymphocytes in vitro. Physiological concentration of thrombin (50 nM) resulted in thromboxane B2 generation from both neutrophils and lymphocytes, which was comparable to that obtained with zymosan activated serum challenge of the cells. Thromboxane B2 generation was dependent on the enzymic region of the thrombin molecule responsible for clotting activity because the complexing of thrombin with hirudin (1:1 U:U mixture of thrombin and hirudin) abolished thromboxane generation from both cell types. Further studies with modified forms of alpha-thrombin (which were produced by irreversible conjugation at the catalytic site and lacked enzymic activity) also showed no generation of thromboxane B2 from neutrophils or lymphocytes. The results indicate that thrombin stimulates thromboxane generation from neutrophils and lymphocytes and that this response is dependent on the proteolytic activity of thrombin.

Animals↗