Search PubMed⌕ Search

Biomedical subjects

J Gibson

Publications and source records attributed to J Gibson.

At least 235 records · Page 13Linked to original sources

Fulminant postsplenectomy sepsis.

The vital role of a normally-functioning spleen in a host's defence against circulating microorganisms has been realized for many years. The fulminant clinical course that characterizes infection with encapsulated microorganisms in asplenic patients is highlighted in these cases of severe pneumococcal sepsis in two patients, 10 and 13 years after splenectomies for idiopathic thrombocytopenic purpura. Approaches to the acute management of septic episodes and preventive measures are discussed. Pneumococcal vaccination reduces the incidence of infection effectively in asplenic patients and has a low complication rate. Penicillin by mouth is also efficacious in this situation, but patient compliance is low. Our current practice is to offer pneumococcal vaccination to all patients who have undergone splenectomy in the past and to administer the vaccine two weeks before elective splenectomies. Asplenic patients should be educated about the potential dangers of a septic episode and should be urged to seek an early medical consultation when this occurs.

Acute Disease↗

Multiple myeloma: relationship between light chain isotype suppression, labelling index of plasma cells, and CD38 expression on peripheral blood lymphocytes.

In this study we have investigated the relationship between the labelling index of plasma cells, the expression of CD38 positive lymphocytes in the peripheral blood, and light chain isotype suppression. This study confirms the relationship between plateau-phase disease and light chain isotype suppression (LCIS) and documents an inverse relationship between LCIS and CD38 positive lymphocytes (.001 less than P less than .01), which is similar to the relationship we have described with the expression of CD10 positive lymphocytes. PCA-1 is rarely expressed in the peripheral blood of patients with myeloma and does not fulfill a role as a marker of active vs. stable disease. There is no relationship between the labelling index of plasma cells and LCIS, because many patients can enter a stage of progressive disease and yet have a labelling index of less than 1% at that time, although a labelling index less than 1% is present in the majority of patients with LCIS. beta-2-microglobulin (beta 2M) also fails to differentiate these two phases of disease in myeloma and does not have a relationship with LCIS, CD38 expression, or CD10 expression. These data suggest that myeloma, like chronic granulocytic leukemia (CGL), can be considered as having two phases of disease: a stable or chronic phase disease, as identified by the presence of LCIS, the absence of CD10 and CD38 positive lymphocytes in the peripheral blood, and a low labelling index, and progressive disease, which is associated with the loss of LCIS and of, CD10 and CD38 positive lymphocytes in the peripheral blood and a high labelling index, although in many cases of progressive disease, the labelling index may also be low. beta 2M does not differentiate between these states.

ADP-ribosyl Cyclase↗

Effects of prolonged versus acute indomethacin therapy in very low birth-weight infants with patent ductus arteriosus.

Indomethacin has proven effective in closing the patent ductus arteriosus (PDA) in most low birth weight (LBW) neonates with this disorder. Early reopening of the ductus is a problem and often leads to the need for surgery. Prolonged use of indomethacin for several days has been suggested as a means to alleviate this problem. The present study was designed to determine if prolonged therapy over 5 days is more effective than a two-dose regimen in preventing reopening of the PDA. Seventy neonates were randomized for either prolonged therapy over 1 week or to receive two doses of indomethacin. All infants were given two doses of indomethacin 0.15 mg per kg, 12h apart. The maintenance group received an additional 0.1 mg per kg daily for 5 days. Ten days after the infants' initial dose of indomethacin, 6 of 22 in the nonmaintenance group as compared to 0 of 22 in the maintenance group had reopening of their ductus arteriosus. Ten infants in the maintenance group eventually had the ductus reopen at a median of 29, range 11-66 days compared to a median of 3, range 2-44 days in the nonmaintenance group. Significantly fewer babies in the maintenance group had a grade II-IV intraventricular hemorrhage compared to the nonmaintenance group. There was no other significant difference in the two groups in the incidence of necrotizing enterocolitis, retrolental fibroplasia or death. Indomethacin given over 5 days is effective for closure of the ductus arteriosus and will prevent reopening until after the acute clinical course in babies under 1500 g; however, the overall incidence of reopening was not different.

Cerebral Hemorrhage↗

Maternal autoimmune disease influences self-tolerance in offspring: the role of suppressor cells and materno-foetal cell traffic.

Autoimmune haemolytic anaemia (AIHA) was induced in normal strain (CBA/Ca/T6) mice by repeated intraperitoneal injection of rat red blood cells (RRBC). Antibody production to cross-reactive antigens on mouse red blood cells (MRBC) and foreign antigens on RRBC was measured by the direct antiglobulin test (DGAT) and serum haemagglutination, respectively. RRBC primed female or male mice and sheep red blood cell (SRBC) primed controls were mated with naive partners and their progeny immunized with RRBC in adult life. The offspring of mothers but not fathers with active autoimmune disease showed a significant reduction in antibody response to self (MRBC) antigens, whereas the response to non-self (RRBC) was unaffected. Transfer of 30 X 10(6) spleen cells from the progeny of RRBC primed mothers into non-irradiated normal recipients resulted in selective suppression of the anti-self response following challenge with RRBC, provided that the cell donors had been boosted with RRBC 7-10 days before the transfer was performed. Thus the progeny of mothers with AIHA possessed self-reactive memory suppressor cells (Ts) shown previously to belong to the Thy-1+ I-J+ Ly-2+ T cell subset in this model. To test whether the Ts were of maternal or foetal origin the suppressor assay was repeated with spleen cells from the F1 offspring of RRBC primed B10.A(3R) (I-Jb) mothers and normal CBA(I-Jk) fathers. Pretreatment with anti-I-Jb serum plus complement completely abrogated suppression on adoptive transfer but anti-I-Jk serum failed to do so, indicating that the Ts were derived from the mothers. These findings emphasize the potential importance of Ts in induction of self tolerance during early ontogeny.

Anemia, Hemolytic, Autoimmune↗

Autoimmune hemolytic anemia: current concepts.

Autoimmune hemolytic anemia (AIHA) is one end of a spectrum of clinical and serological disorders resulting from an autoimmune attack against red cells. Although the etiology of this disorder is far from firmly established, the pathogenesis of red cell destruction by the effector mechanisms of the immune system is well characterised and correlates well with the clinical and serological features of this disorder. Direct antiglobulin test (DAGT) negative AIHA, production crises, AIHA in children and following alpha methyldopa therapy are subgroups of AIHA which have recently been described or more clearly defined and understood. The addition of high dose immunoglobulin and danazol as well as the potential use of more novel approaches to the traditional triad of corticosteroids, splenectomy and immunosuppressive agents has expanded and increased the flexibility of the therapeutic options in this disorder.

Anemia, Hemolytic, Autoimmune↗

Red cell ferritin and iron stores in patients with chronic disease.

Serum and red cell ferritin were determined in a heterogeneous group of 59 patients with chronic disease undergoing a bone marrow biopsy. There was very little correlation between serum and red cell ferritin (r = 0.53). Although serum ferritin increased in relation to increased bone marrow iron stores, only 1 out of 8 patients with absent marrow iron stores and none of 8 patients with reduced marrow iron stores had a decreased serum ferritin. In contrast, 6 of 8 patients with absent iron stores had a reduced red cell ferritin concentration. There was no significant difference between the mean red cell ferritin of the patients with reduced, normal and mild-moderately increased marrow iron stores (30, 26 and 34 ag/cell). Red cell ferritin was decreased in 78% of a group of 32 patients with a low mean cell volume. In the patients studied, red cell ferritin was a better indicator of absent iron stores than serum ferritin. However, red cell ferritin did not detect a reduction in the iron status until the marrow iron stores were completely depleted. Apparently, during normal erythropoiesis the primitive erythroblasts continue to take up iron irrespective of the amount of iron available in the stores.

Adolescent↗

Anaerobic and aerobic metabolism of diverse aromatic compounds by the photosynthetic bacterium Rhodopseudomonas palustris.

The purple nonsulfur photosynthetic bacterium Rhodopseudomonas palustris used diverse aromatic compounds for growth under anaerobic and aerobic conditions. Many phenolic, dihydroxylated, and methoxylated aromatic acids, as well as aromatic aldehydes and hydroaromatic acids, supported growth of strain CGA001 in both the presence and absence of oxygen. Some compounds were metabolized under only aerobic or under only anaerobic conditions. Two other strains, CGC023 and CGD052, had similar anaerobic substrate utilization patterns, but CGD052 was able to use a slightly larger number of compounds for growth. These results show that R. palustris is far more versatile in terms of aromatic degradation than had been previously demonstrated. A mutant (CGA033) blocked in aerobic aromatic metabolism remained wild type with respect to anaerobic degradative abilities, indicating that separate metabolic pathways mediate aerobic and anaerobic breakdown of diverse aromatics. Another mutant (CGA047) was unable to grow anaerobically on either benzoate or 4-hydroxybenzoate, and these compounds accumulated in growth media when cells were grown on more complex aromatic compounds. This indicates that R. palustris has two major anaerobic routes for aromatic ring fission, one that passes through benzoate and one that passes through 4-hydroxybenzoate.

Aerobiosis↗

Purification and properties of benzoate-coenzyme A ligase, a Rhodopseudomonas palustris enzyme involved in the anaerobic degradation of benzoate.

A soluble benzoate-coenzyme A (CoA) ligase was purified from the phototrophic bacterium Rhodopseudomonas palustris. Synthesis of the enzyme was induced when cells were grown anaerobically in light with benzoate as the sole carbon source. Purification by chromatography successively on hydroxylapatite, phenyl-Sepharose, and hydroxylapatite yielded an electrophoretically homogeneous enzyme preparation with a specific activity of 25 mumol/min per mg of protein and a molecular weight of 60,000. The purified enzyme was insensitive to oxygen and catalyzed the Mg2+ ATP-dependent formation of acyl-CoA from carboxylate and free reduced CoA, with high specificity for benzoate and 2-fluorobenzoate. Apparent Km values of 0.6 to 2 microM for benzoate, 2 to 3 microM for ATP, and 90 to 120 microM for reduced CoA were determined. The reaction product, benzoyl-CoA, was an effective inhibitor of the ligase reaction. The kinetic properties of the enzyme match the kinetics of substrate uptake by whole cells and confirm a role for benzoate-CoA ligase in maintaining entry of benzoate into cells as well as in catalyzing the first step in the anaerobic degradation of benzoate by R. palustris.

Anaerobiosis↗

von Willebrand's disease characterized by increased ristocetin sensitivity and the presence of all von Willebrand factor multimers in plasma: a new subtype.

The clinical and laboratory features of a patient with a recently recognized new variant of von Willebrand's disease are presented. The importance of this variant is that it is associated with a clinically significant bleeding diathesis but with a normal skin bleeding time, PTTK, factor VIIIc and platelet aggregation with 1 mg/ml ristocetin. The distinctive laboratory features are increased platelet sensitivity to low concentrations of ristocetin, and the presence of all plasma von Willebrand factor multimers, but in reduced amounts. The need for thorough investigation of patients with significant bleeding history despite apparently normal screening tests is emphasized.

Adult↗

In vitro properties of murine autoreactive T cell clones with specificity for erythrocytes.

A panel of IL-2 dependent T cell clones was generated from the lymph nodes of Balb/c mice immunized with RRBC which carry both foreign determinants specific for RRBC and crossreactive determinants shared with MRBC. From this panel, two clones designated L1R1 41 and L2R1 10 were successfully maintained in long-term culture for over six months and possessed essentially similar properties. They were slow growing and secreted a late-acting B cell growth factor but neither BSF-1 (Il-4) nor gamma interferon. Although Thy-1+ they were negative for other differentiation antigens including Ly-1, Ly-2 and L3T4. Both clones underwent antigen dependent proliferation in vitro. At a T cell:irradiated spleen cell ratio of 1:10 they responded to RRBC and MRBC equally well whereas at a ratio of 10:1 only an anti-self response was obtained. These results illustrate how antigen presentation may influence the capacity of the immune system to discriminate between self and non-self.

Animals↗

Post bone marrow transplant sera and persisting mast cell colonies.

Serum samples were collected from eight recipients of allogeneic bone marrow transplants (BMT) following the normalization of peripheral blood counts. Three patients (11 samples) were in the early engraftment period (less than 6 months post-BMT) and still receiving cyclosporin A or methotrexate and the remaining five patients (18 samples) were in stable engraftment (12-84 months post-BMT) and not on immunosuppressive therapy. All post-BMT serum samples supported the growth of increased numbers of mast cell colonies in long-term agar cultures when compared with normal controls (p less than 0.025-0.005), irrespective of the time from BMT or the presence of clinical graft-versus-host disease (GVHD). In contrast, the numbers of neutrophil, monocyte and eosinophil colonies were equivalent in test and control groups. It is proposed that post-BMT sera contain higher levels of a mast cell stimulating activity(s) than does normal sera. Such increased levels might be associated with clinical or subclinical GVHD.

Blood Physiological Phenomena↗

Permeability of ammonia and amines in Rhodobacter sphaeroides and Bacillus firmus.

Permeabilities of uncharged ammonia (NH3), methylamine (CH3NH2), and ethylamine (CH3CH2NH2) in the gram-negative phototrophic bacterium Rhodobacter sphaeroides were measured directly in cells grown heterotrophically under aerobic conditions. The permeability of NH3 was 2.55 +/- 0.73 microns s-1 (n = 20), but the permeabilities of CH3NH2 (MA) and CH3CH2NH2 (EA) were higher, PMA = 17.8 +/- 2.8 microns s-1 (n = 50), PEA = 24.7 +/- 3.9 microns s-1 (n = 44). The relative permeabilities of amines were also determined from their effect on the pH gradient across the cell membrane at alkaline external pH. In aerobically grown R. sphaeroides, both techniques indicated that the permeability of CH3CH2NH2 was about 30% greater than that of CH3NH2 but that the permeability of NH3 was only about 1/5 that of CH3NH2. The relative permeabilities of NH3 (A) and CH3NH2 were different in R. sphaeroides cells grown under three different physiological conditions: (a) cells grown aerobically with ammonium sulfate (PA/PMA about 0.20), (b) cells grown anaerobically with ammonium sulfate as their nitrogen source (PA/PMA about 0.29), and (c) diazotrophic cells (PA/PMA about 0.38). NH3 was also found to be only about 1/3 as permeable as CH3NH2 in the alkalophilic gram-positive bacterium Bacillus firmus. The findings that permeability properties of NH3 and CH3NH2 are very different in different bacteria and vary according to the conditions under which the organism is grown need to be taken into account in the interpretation of experiments where [14C]methylamine is used as an ammonia analog.

Aerobiosis↗