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Biomedical subjects

M Martin

Publications and source records attributed to M Martin.

At least 469 records · Page 26Linked to original sources
PubMed1993

A novel cellular model (SPGM 1) of switching between the pre-B cell and myelomonocytic lineages.

The suspension pro granulocyte/macrophage (SPGM1) cell line was established from a transplantable mouse progranulocytic/promacrophage tumor. Surprisingly, SPGM1 cells expressed a typical CD5 pre-B cell phenotype, being positive for Ly-1 (CD5), PB76, B220 (CD45RA), and the pre-B Ig receptor complex (microH chains, lambda 5 and vpre-B surrogate L chains, and the IgM alpha (mb-1) and Ig beta (B29) co-receptor molecules). Southern Blot analysis revealed clonal rearrangement of the microH chain locus and germ-line L chain loci. SPGM1 formed blast cell-, macrophage-, and occasional granulocytic colonies in soft agar in the presence of murine IL-3. IL-3 also induced macrophage differentiation of SPGM1 cells in suspension cultures. The earliest changes were detectable at 24 h by Northern blot analysis. IL-3-treatment increased Mac1 mRNA, induced c-fms mRNA, and down-regulated mRNA for mu, lambda 5, vpre-B and mb-1. After 2 to 4 days the cells were larger, strongly adherent, expressed the macrophage markers Mac1 and F4/80, had lost microH chain and PB76 surface expression, and readily phagocytosed latex beads. Thus SPGM1 has all the characteristic features of a CD5+ pre-B cell line. However, IL-3 predominantly induced SPGM1 to switch its differentiation program from a pre-B cell to a macrophage. This inducible, rapid switch of virtually the entire population provides a unique model for the molecular analysis of mechanisms involved in cell-fate determination.

Animals↗
PubMed1993

Surface phenotype and functions of tumor-infiltrating dendritic cells: CD8 expression by a cell subpopulation.

Although the function and significance of tumor-infiltrating dendritic cells (TIDC) in the immune response to tumor have never been clearly demonstrated, their location suggests that they play a critical role in the presentation of tumor antigen to specific T cells. We studied the morphological and functional characteristics of interstitial dendritic cells (DC) located inside tumors obtained by injection of cancer cells into syngeneic rats. Single and double immunostaining of tumor sections revealed a dense network of cells which expressed class II major histocompatibility complex (MHC II) molecules. Cell morphology and surface markers were characteristic of DC populations in other tissues. These DC were in close contact with tumor cells and increased in number as the tumor grew larger. Unexpectedly, a subpopulation of morphologically characteristic TIDC expressed both CD8 and MHC II molecules. TIDC were purified from tumors by gradient centrifugation and immunobeads and characterized by morphology, ultrastructural study and surface markers studied by flow cytometry. TIDC were negative for the CD5 molecule (a pan T cell marker), and were not labeled with 3.2.3 monoclonal antibody (mAb) (an NK cell marker) or with Ki-M2R mAb (a macrophage marker). A subpopulation of TIDC expressed the CD8 molecule, confirming the in situ results. TIDC expressed high levels of class I and class II MHC molecules and the adhesion molecule ICAM-1. This expression is compatible with effective antigen presenting function. Purified TIDC triggered rapid and high levels of proliferation of tumor-immune T cells in vitro, demonstrating the potential of these cells to constitutively process and present tumor-associated antigens.

Animals↗
PubMed1993

N-acetyl-L-aspartate and acetate 1H NMR signal overlapping under mild acidic pH conditions.

The pH dependence of methyl proton chemical shifts of acetate, acetoacetate, N-acetyl-L-aspartate (NAA), and N-acetyl-L-aspartyl-L-glutamate (NAAG) were studied from pH 3 to pH 9. Only slight shifts of acetoacetate, NAA, and NAAG methyl signals were observed, whereas the acetate signal was largely shifted as a result of the titration of its acidic function. At pH 4.7, acetate and NAA methyl signals overlapped, whereas at more acidic pH, the acetate signal appeared downfield when compared to that of NAA. Results are discussed in terms of spectra misinterpretation risks linked to uncontrolled sample pH, on the one hand, and in terms of pH control and contamination by exogenous acetate during perchloric acid cell extract preparation, on the other.

Acetates↗
PubMed1993

PHLECO: a multicenter study of the fate of 1647 hospital patients treated conservatively without fibrinolysis and surgery.

The PHLECO Study (phlebothrombosis conservative therapy) is a multicenter investigation of patients with deep vein thrombosis receiving conservative nonfibrinolytic hospital treatment. A second study (part II: PHLEFI, phlebothrombosis fibrinolytic treatment) to be published later deals with the outcome of fibrinolytic therapy. In both studies the incidence of life-threatening sequelae, such as pulmonary embolism, is of major interest. The 49 medical departments participating in the study mailed the relevant data to the Duisburg Coordination Center for further data analysis and the following information was gained: (a) In descending order of frequency, the clinical conditions of thrombosis were: immobility, postoperative status, malignancy, hormone treatment, posttraumatic conditions, and pregnancy. (b) In descending order of frequency, the sites of thrombosis were: femoral vein, calf vein, iliac vein, popliteal vein, and subclavian vein. Left-sided thrombosis predominated in the iliac and subclavian vein groups. (c) In descending order of frequency, the treatment regimens employed were: intravenous heparin+oral anticoagulants, intravenous heparin+subcutaneous heparin, intravenous heparin alone, subcutaneous heparin alone, intravenous heparin+subcutaneous heparin+oral anticoagulants, subcutaneous heparin+oral anticoagulants, intravenous heparin+platelet aggregation inhibitors. (d) The average hospital stay was 23.7 +/- 15.6 days. No correlation existed between duration of hospital stay and particular types of therapy. (e) The incidence of nonfatal pulmonary embolism was 16.1% while that of fatal pulmonary embolism was 2.33%. (f) Women outnumbered men in the group with fatal pulmonary embolism, and the death rate among older patients was higher than that among younger patients. (g) Patients with fatal pulmonary embolism had a shorter history of thrombosis than patients in the unselected cohort (patients with and without pulmonary embolism).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1993

Analysis of the frequency of inheritance of transposed Ds elements in Arabidopsis after activation by a CaMV 35S promoter fusion to the Ac transposase gene.

The Ac/Ds transposon system of maize shows low activity in Arabidopsis. However, fusion of the CaMV 35S promoter to the transposase gene (35S::TPase) increases the abundance of the single Ac mRNA encoded by Ac and increases the frequency of Ds excision. In the experiments reported here it is examined whether this high excision frequency is associated with efficient re-insertion of the transposon. This was measured by using a Ds that carried a hygromycin resistance gene (HPT) and was inserted within a streptomycin resistance gene (SPT). Excision of Ds therefore gives rise to streptomycin resistance, while hygromycin resistance is associated with the presence of a transposed Ds or with retention of the element at its original location. Self-fertilisation of most individuals heterozygous for Ds and 35S::TPase produced many streptomycin-resistant (strep(r)) progeny, but in many of these families a small proportion of strep(r) seedlings were also resistant to hygromycin (hyg(r)). Nevertheless, 70% of families tested did give rise to at least one strep(r), hyg(r) seedling, and over 90% of these individuals carried a transposed Ds. In contrast, the Ac promoter fusion to the transposase gene (Ac::TPase) produced fewer strep(r)hyg(r) progeny, and only 53% of these carried a transposed Ds. However, a higher proportion of the strep(r) seedlings were also hyg(r) than after activation by 35S::TPase. We also examined the genotype of strep(r), hyg(r) seedlings and demonstrated that after activation by 35S::TPase many of these were homozygous for the transposed Ds, while this did not occur after activation by Ac::TPase. From these and other data we conclude that excisions driven by 35S::TPase usually occur prior to floral development, and that although a low proportion of strep(r) progeny plants inherit a transposed Ds, those that do can be efficiently selected with an antibiotic resistance gene contained within the element. Our data have important implications for transposon tagging strategies in transgenic plants and these are discussed.

Arabidopsis↗
PubMed1993

Impaired cytokine production in whole blood cell cultures of patients with urological carcinomas.

The production of the cytokines interferon gamma (IFN gamma), interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor alpha (TNF alpha) was investigated in the mitogen-stimulated whole blood cell culture media from 51 patients with urinary bladder carcinomas, 52 patients with renal carcinomas, 31 patients with prostatic carcinomas and 360 healthy controls. The cytokines were measured 4 days after induction by a sensitive enzymo-immunological assay. In the blood cell culture supernatants of the patients with urinary bladder carcinomas significant lower levels of IFN gamma (P < or = 0.001), IL-2 (P < or = 0.01) and TNF alpha (P < or = 0.05) were found as compared to the controls. Blood cells of patients with renal carcinomas had lower production of IFN gamma (P < or = 0.01), IL-2 (P < or = 0.001) and IL-1 alpha (P < or = 0.01), whereas the values of the total group of patients with prostatic carcinomas were not significantly different from those of the controls. Lymphocyte and monocyte counts were almost identical in the control and all tumor patient groups. When the patients with renal carcinomas and prostatic carcinomas were analyzed according to their different clinical stages we could show a gradual depression of the IFN-gamma levels, which was related to tumor burden.

Aged↗
PubMed1993

Randomized trial of dapsone and aerosolized pentamidine for the prophylaxis of Pneumocystis carinii pneumonia and toxoplasmic encephalitis.

PURPOSE: Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis are the most frequent pulmonary and central nervous system opportunistic infections associated with human immunodeficiency virus (HIV) infection. We designed a prospective study to compare the effects of aerosolized pentamidine and dapsone in the prophylaxis of these infections in HIV-infected persons with CD4+ lymphocyte counts less than 250/mm3. PATIENTS AND METHODS: Two hundred seventy-eight patients seropositive for HIV who had acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex were randomly assigned to receive intermittent dapsone (100 mg twice weekly) or aerosolized pentamidine (100 mg every 2 weeks). The proportion of patients remaining free of PCP or toxoplasmosis was analyzed with the log-rank test as a function of time, as were the effects of zidovudine or prophylaxis on survival. RESULTS: Dapsone and aerosolized pentamidine demonstrated similar efficacy in the primary and secondary prophylaxis of PCP, with 15 (18%) failures among patients receiving dapsone compared to 15 (14%) among those receiving aerosolized pentamidine (p = 0.4), after a mean length of follow-up of 42 and 44 weeks, respectively. Dapsone was more effective in the primary prophylaxis of toxoplasmic encephalitis, with six toxoplasmic encephalitis events occurring among those receiving aerosolized pentamidine, compared to none among those taking dapsone (p = 0.01). Primary prophylaxis for PCP was more effective than secondary prophylaxis with either therapy. Zidovudine therapy did not prevent PCP yet prolonged the PCP-free interval for those in whom either prophylactic therapy failed. Kaplan-Meier estimates did not show a difference in survival between the patients receiving either therapy, yet zidovudine use was associated with improved survival, independent of race and risk factor (Cox proportional hazards model, p = 0.001). The 1-month survival for patients developing PCP despite prophylaxis was better with those in whom dapsone failed than it was for those in whom aerosolized pentamidine failed (p = 0.08). CONCLUSION: Dapsone is as effective as aerosolized pentamidine in preventing PCP and has the advantage of a lower cost, easier administration, and possibly an additional preventive effect against toxoplasmosis. Zidovudine prolongs the PCP-free interval for patients receiving prophylaxis, regardless of which prophylactic agent is used.

AIDS-Related Opportunistic Infections↗
PubMed1993

Osmosis: a microcomputer laboratory teacher.

A computer simulation of osmotic processes has been developed. Several experimental setups are graphically simulated and may be freely selected by the user. The simulation analyzes the basic factors which determine the osmotic pressure and volume flow of a solution (e.g. concentration, temperature, activity coefficient, Staverman's coefficient and external pressure). The program was written in Turbo Pascal to operate in IBM-PCs or compatibles. High quality graphical display of results maintains the students' interest. A user's guide and continuous help for the available options simplify its use. Computer simulation seems to be a very well suited aid for teaching osmotic phenomena, improving both theoretical knowledge and the ability of the students to empirically demonstrate some of the basic laws of osmotic phenomena.

Animals↗
PubMed1993

Involvement of T lymphocytes in curative effect of a new immunomodulator OM 163 on rat colon cancer metastases.

In a model of colon cancer in syngeneic rats, a new immunomodulator, OM 163, induced the complete disappearance of peritoneal carcinomatosis (nodules measuring 1-5 mm) in 41 out of 82 rats. Those results were confirmed in a survival experiment in which 3 out of 10 treated rats died free of tumour 10, 18 and 28 months after the tumour cell injection while all the untreated control rats died of their tumours within 3 months. OM 163 had a systemic effect, since injected intraperitoneally it completely inhibited the growth of lung metastases in 13 out of 20 rats. The antitumour effect of OM 163 was also observed in two rat strains on original tumours. Lymphocyte infiltration was observed in the tumours mainly constituted of CD4+ and CD8+ cells. The treatment had no effect in nude rats, confirming the involvement of T lymphocytes. Furthermore, rats cured by OM 163 were protected against a second challenge of tumour cells and in a Winn's assay, splenocytes from cured rats protected normal rats against tumour cells.

Adjuvants, Immunologic↗
PubMed1993

Selection of emergency medicine residents.

The selection of emergency medicine residents requires review of medical school performance and, usually, an interview in which applicants and program directors exchange important information. Computer technology is available to assist programs in the analysis of information about applicants. Ethnic diversity and minority recruitment should also be considered as 40% of all emergency medicine residencies have no minority residents. Suggestions for developing a valid, humane, and fair selection process are made.

Educational Status↗
PubMed1993

The pharmacokinetics of recombinant human relaxin in nonpregnant women after intravenous, intravaginal, and intracervical administration.

The pharmacokinetics of recombinant human relaxin (rhRlx) after intravenous (iv) bolus administration and the absorption of rhRlx after intracervical or intravaginal administration were determined in nonpregnant women. The study was conducted in two parts. In part I, 25 women received 0.01 mg/kg rhRlx iv. After a minimum 7-day washout period, these women were dosed intracervically (n = 10) or intravaginally (n = 15) with 0.75 or 1.5 mg rhRlx, respectively, in 3% methylcellulose gel. Part II was a double-blind, randomized, three-way crossover study in 26 women. At 1-month intervals, each woman received one of three intravaginal treatments consisting of 0 (placebo), 1, or 6 mg rhRlx in 3% methylcellulose gel. The serum concentrations of relaxin following iv administration were described as the sum of three exponentials. The mean (+/- SD) initial, intermediate, and terminal half-lives were 0.09 +/- 0.04, 0.72 +/- 0.11, and 4.6 +/- 1.2 hr, respectively. Most of the area under the curve was associated with the intermediate half-life. The weight-normalized clearance was 170 +/- 50 mL/hr/kg. The observed peak concentration was 98 +/- 29 ng/mL, and the weight-normalized initial volume of distribution was 78 +/- 40 mL/kg, which is approximately equivalent to the serum volume. If central compartment elimination was assumed, the volume of distribution at steady state (Vss/W) was 280 +/- 100 mL/kg, which is approximately equivalent to extracellular fluid volume. Vss/W could be as large as 1300 +/- 400 mL/kg without this assumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intravaginal↗
PubMed1993

An anti-EnaTS detected in the serum of an MiI homozygote.

The serum of EH reacted with all red cells (RBCs) except her own, ficin- or trypsin-treated red cells, and En(a-) red cells. This reactivity defined an anti-EnaTS specificity. The red cells of the proposita typed as M-N+S-S+, Vw+Mur-Hil-Hut-Anek-Lane-, Wr(a-b+), EnaKT+. Red cells of five relatives were Vw+ and positive with her serum. Titration studies suggest that EH is genetically an MiI homozygote and that her Vw+ relatives are MiI heterozygotes. There is no history of consanguinity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting studies have agreed with the serologic observations. A variant sialoglycoprotein of faster mobility than normal glycoprotein A, but no normal glycoprotein A, was detected on her red cells. Treatment with N-glycanase did not alter the mobility, which indicated that there was no N-glycosylation of residue 26. These findings are in agreement with the reported properties of the Mi.I-specific glycoprotein A. The relatives' Vw+ red cells showed the variant sialoglycoprotein and normal glycoprotein A. EH appears to be the first reported MiI homozygote.

Aged↗
PubMed1993

The impact of blood transfusion on the occurrence of pneumonitis in primary cytomegalovirus infection after liver transplantation.

The influence of blood transfusion, and particularly the transfusion of blood from cytomegalovirus (CMV)-seropositive donors, on the incidence of primary CMV infection following liver transplantation was studied prospectively in 29 consecutive CMV-seronegative adult liver transplant recipients. Fourteen patients received a liver graft from a CMV-seropositive donor (Group A), whereas for 15 patients, the donor was CMV seronegative (Group B). Eleven patients (79%) in Group A but only two (13%) in Group B developed CMV infection (odds ratio, 23.8; 95% confidence interval, 3.5-169.4). In five Group A patients, primary CMV infection resulted in pneumonitis. There was no statistical difference in the total number of blood units and the number of units of CMV-seropositive blood given to patients who did or did not develop CMV infection in both Groups A and B (odds ratio for unit of CMV-seropositive blood transfused, 1.07; 95% confidence interval, 0.96-1.19). However, Group A patients who developed CMV pneumonitis received a higher total number of blood units (median, 44) and of CMV-seropositive blood units (median, 18) than did patients who developed other CMV infections (asymptomatic CMV, CMV syndrome, or CMV hepatitis), who received a median of 9 total units of blood and 5 units of CMV-seropositive blood (p = 0.004). It is concluded that the total number of blood units and of CMV-seropositive blood units transfused does not have an effect on the incidence of primary CMV infection after liver transplantation, but it does have an impact on the severity of the infection in recipients of a CMV-seropositive allograft.

Blood Transfusion↗
PubMed1993

Adult respiratory distress syndrome secondary to end-stage liver disease-successful outcome following liver transplantation.

The adult respiratory distress syndrome (ARDS) complicating liver failure carries a 100% mortality. Two cases of ARDS that resolved following liver transplantation have been reported, one associated with acute allograft rejection, and the second due to sepsis. There is, however, a great reluctance to transplant these very-high-risk patients. We report the first series of patients with ARDS secondary to liver failure who successfully underwent OLTX. No patient had sepsis or pneumonia. Posttransplant mechanical ventilation was required for a median of 14 days (range 6-37 days). All patients in this series are alive and well, with a follow-up of 6-15 months. This demonstrates that ARDS associated with liver failure, an otherwise uniformly lethal complication, can respond dramatically to OLTX.

Adolescent↗
PubMed1993

The influence of HLA matching on cytomegalovirus hepatitis and chronic rejection after liver transplantation.

Previous findings in liver transplantation patients have raised the concept that HLA plays a dualistic role. HLA matching will reduce rejection but may augment MHC restricted cellular immune mechanisms of liver allograft injury. To evaluate this concept, we studied CMV hepatitis in 399 FK506-treated liver transplant patients, including 355 cases for which complete HLA-A,B,DR,DQ typing information was available. CMV hepatitis developed in 25 patients, and 17 of them (or 68%) showed a one or two HLA-DR antigen match with the donor. In contrast, HLA-DR matches were found in only 35% of 330 patients without CMV hepatitis (P = 0.005). No significant associations were seen for HLA-A, HLA-B, and HLA-DQ antigens. In pretransplant CMV-seronegative patients with seropositive grafts (n = 39), the frequency of CMV hepatitis was 44% for HLA-DR-matched livers but 14% for HLA-DR-unmatched livers. In seropositive recipients (n = 187), these frequencies were 12% and 2% for HLA-DR-matched and unmatched liver grafts. Chronic rejection developed in 29 patients (or 8%) during a follow-up between 10 and 24 months after transplantation. Its incidence was higher in the CMV hepatitis group (24% vs. 6%) (P = 0.007). Although no associations were found between HLA matching and the incidence of chronic rejection, there was an earlier onset of chronic rejection of HLA-DR-matched livers irrespective of CMV hepatitis. These findings suggest that an HLA-DR match between donor and recipient increases the incidence of CMV hepatitis in both primary and secondary CMV infections. Although HLA compatibility leads to less acute cellular rejection, it is suggested that DR matching may accelerate chronic rejection of liver transplants, perhaps through HLA-DR-restricted immunological mechanisms toward viral antigens, including CMV.

Chronic Disease↗
PubMed1993

Specific intravenous carbohydrate therapy. A new concept in inhibiting antibody-mediated rejection--experience with ABO-incompatible cardiac allografting in the baboon.

Heterotopic allografting of ABO-incompatible donor hearts in recipient baboons "hyperimmunized" against the incompatible A or B antigen (n = 3) was followed by hyperacute antibody-mediated vascular rejection within a mean of 19 min. The A and B epitopes against which these antibodies are directed are carbohydrates that can be synthesized. The continuous i.v. infusion of the specific synthetic A or B trisaccharide, beginning immediately pre-transplant and continued posttransplant for several days, prolonged allograft survival to a mean of 8 days (n = 2) and prevented antibody-mediated rejection, graft failure resulting from acute cellular rejection. The addition of triple pharmacologic immunosuppressive therapy (n = 4) resulted in prolongation of graft survival to a mean of > 28 days, with one heart still beating at 52 days; all grafts showed features of cellular rejection. "Accommodation" would appear to have developed in several baboons as graft function continued for periods of up to 39 days after discontinuation of carbohydrate therapy. Specific i.v. carbohydrate therapy should allow organ allografting to be performed across the ABO blood group barrier in humans. Furthermore, if the carbohydrate epitopes on the organs of discordant animals (e.g., the pig) against which human xenoreactive antibodies are directed can be confirmed, then this form of therapy might allow successful discordant organ xenotransplantation in man.

ABO Blood-Group System↗