Spontaneous regression of acquired C1 esterase inhibitor deficiency associated with splenic marginal zone lymphoma presenting with recurrent angio-oedema.

A 52 year old woman with marginal zone lymphoma developed recurrent episodes of angio-oedema and was found to have C1 esterase inhibitor deficiency. She declined chemotherapy for the lymphoma. Fourteen months after her initial presentation she was found to be in partial remission, and this was confirmed by peripheral blood film and bone marrow examinations. This was associated with normalisation of C1 esterase inhibitor, C1q, and C4 values. Regression of acquired C1 esterase inhibitor deficiency associated with spontaneous partial remission of lymphoma has not been reported previously.

Cell cycle roles for two 14-3-3 proteins during Drosophila development.

Drosophila 14-3-3 epsilon and 14-3-3 zeta proteins have been shown to function in RAS/MAP kinase pathways that influence the differentiation of the adult eye and the embryo. Because 14-3-3 proteins have a conserved involvement in cell cycle checkpoints in other systems, we asked (1) whether Drosophila 14-3-3 proteins also function in cell cycle regulation, and (2) whether cell proliferation during Drosophila development has different requirements for the two 14-3-3 proteins. We find that antibody staining for 14-3-3 family members is cytoplasmic in interphase and perichromosomal in mitosis. Using mutants of cyclins, Cdk1 and Cdc25(string) to manipulate Cdk1 activity, we found that the localization of 14-3-3 proteins is coupled to Cdk1 activity and cell cycle stage. Relocalization of 14-3-3 proteins with cell cycle progression suggested cell-cycle-specific roles. This notion is confirmed by the phenotypes of 14-3-3 epsilon and 14-3-3 zeta mutants: 14-3-3 epsilon is required to time mitosis in undisturbed post-blastoderm cell cycles and to delay mitosis following irradiation; 14-3-3 zeta is required for normal chromosome separation during syncytial mitoses. We suggest a model in which 14-3-3 proteins act in the undisturbed cell cycle to set a threshold for entry into mitosis by suppressing Cdk1 activity, to block mitosis following radiation damage and to facilitate proper exit from mitosis.

The schedule of destruction of three mitotic cyclins can dictate the timing of events during exit from mitosis.

BACKGROUND: Degradation of the mitotic cyclins is a hallmark of the exit from mitosis. Induction of stable versions of each of the three mitotic cyclins of Drosophila, cyclins A, B, and B3, arrests mitosis with different phenotypes. We tested a recent proposal that the destruction of the different cyclins guides progress through mitosis. RESULTS: Real-time imaging revealed that arrest phenotypes differ because each stable cyclin affects specific mitotic events differently. Stable cyclin A prolonged or blocked chromosome disjunction, leading to metaphase arrest. Stable cyclin B allowed the transition to anaphase, but anaphase A chromosome movements were slowed, anaphase B spindle elongation did not occur, and the monooriented disjoined chromosomes began to oscillate between the spindle poles. Stable cyclin B3 prevented normal spindle maturation and blocked major mitotic exit events such as chromosome decondensation but nonetheless allowed chromosome disjunction, anaphase B, and formation of a cytokinetic furrow, which split the spindle. CONCLUSIONS: We conclude that degradation of distinct mitotic cyclins is required to transit specific steps of mitosis: cyclin A degradation facilitates chromosome disjunction, cyclin B destruction is required for anaphase B and cytokinesis and for directional stability of univalent chromosome movements, and cyclin B3 degradation is required for proper spindle reorganization and restoration of the interphase nucleus. We suggest that the schedule of degradation of cyclin A, cyclin B, and then cyclin B3 contributes to the temporal coordination of mitotic events.

Arabidopsis mutants lacking the 43- and 54-kilodalton subunits of the chloroplast signal recognition particle have distinct phenotypes.

The chloroplast signal recognition particle (cpSRP) is a protein complex consisting of 54- and 43-kD subunits encoded by the fifty-four chloroplast, which encodes cpSRP54 (ffc), and chaos (cao) loci, respectively. Two new null alleles in the ffc locus have been identified. ffc1-1 is caused by a stop codon in exon 10, while ffc1-2 has a large DNA insertion in intron 8. ffc mutants have yellow first true leaves that subsequently become green. The reaction center proteins D1, D2, and psaA/B, as well as seven different light-harvesting chlorophyll proteins (LHCPs), were found at reduced levels in the young ffc leaves but at wild-type levels in the older leaves. The abundance of the two types of LHCP was unaffected by the mutation, while two others were increased in the absence of cpSRP54. Null mutants in the cao locus contain reduced levels of the same subset of LHCP proteins as ffc mutants, but are distinguishable in four ways: young leaves are greener, the chlorophyll a/b ratio is elevated, levels of reaction center proteins are normal, and there is no recovery in the level of LHCPs in the adult plant. The data suggest that cpSRP54 and cpSRP43 have some nonoverlapping roles and that alternative transport pathways can compensate for the absence of a functional cpSRP.

Expression of a dominant negative form of cpSRP54 inhibits chloroplast biogenesis in Arabidopsis.

The chloroplast homolog of the 54 kDa subunit of signal recognition particle is required for the in vitro targeting of chlorophyll a/b binding proteins (LHCP) to the thylakoid membrane. To explore the function of cpSRP54 in vivo, plants that are mutated in cpSRP54 function were generated. Dominant negative forms of cpSRP54 altered in single amino acids within the conserved guanine nucleotide binding domain were expressed in Arabidopsis. Transformed plants contained less than 30% of the wild-type level of cpSRP54 protein. As a consequence of the reduced cpSRP54 protein content, the first emerging leaves were yellow and contained immature chloroplasts. Although the chlorophyll (chl) content of the leaves was reduced by 75%, the chl a/b ratio was unaffected, indicating a role of cpSRP54 in the biogenesis of proteins besides LHCP. Many chloroplast proteins were less abundant in the first emerging leaves, including non-pigmented proteins, thylakoid proteins known to be targeted by alternative pathways, and soluble proteins. These observations indicate that the cpSRP54 mutation also has a pleiotropic effect on chloroplast biogenesis. Whereas the level of cpSRP54 remained low as the plants aged, leaves emerging subsequently had a wild-type appearance, suggesting that the adult plants compensated for the reduction in cpSRP54 protein.

Cutaneous lesions in a case of acute megakaryoblastic leukaemia.

We describe the case of a 68-year-old woman who presented with asymptomatic skin nodules and symptoms of anaemia, and was found to have acute megakaryoblastic leukaemia with fibrosis, a condition now believed to correspond to the former diagnosis of acute myelofibrosis. There is only one previous report of skin lesions developing in this condition.

Tracheoesophageal fistula after chemotherapy for lymphoma.

We present a case of tracheoesophageal fistula that occurred after chemotherapy for stage IV B Hodgkin's lymphoma. We outline our surgical management of the case and advocate the use of a single-stage repair in selected cases.

Acquired angioedema.

An unusual case of angioedema is presented. The initial presentation occurred at 84 years-of-age without a family history of this condition. Further investigation revealed an underlying lymphoproliferative disorder which was associated with an acquired deficiency of the complement component C1 esterase inhibitor. It is important to distinguish this condition from the hereditary form.

Familial haemostatic defect associated with reduced prothrombin consumption.

Ten individuals from three unrelated families suffered from an usual inherited haemorrhagic disorder. The defect was associated with reduced prothrombin conversion as shown by a grossly abnormal prothrombin consumption index. All known plasma coagulation factors were present in adequate concentrations but in the two families tested the results were consistent with a defect of the interaction between plasma and platelets or phospholipid. Some of the affected family members exhibited a mild bleeding tendency characterized by post-operative or post-partum haemorrhage but none suffered spontaneous bleeding. In therapeutic trials in one of the patients both plasma and platelet transfusions were needed in order to correct the abnormality. This finding together with in vitro and other in vivo studies indicated that the abnormality is associated with an inhibitor of the interaction between plasma and phospholipid during blood coagulation. The results suggest the possibility of an abnormality of the gamma-carboxyglutamic acid residues of one or more vitamin K dependent coagulation factors but immunological and electrophoretic studies have so far failed to detect this. The findings underline the importance of a test of prothrombin conversion in screening procedures for an otherwise unexplained bleeding disorder.

Factor VIII inhibitor and bronchogenic carcinoma.

An inhibitor to procoagulant factor VIII (FVIIIC) developed in a patient three years after palliative resection of a bronchogenic carcinoma. The inhibitor was not active against ristocetin cofactor but possibly had some activity against factor XI. It responded to immunosuppressive therapy. This is apparently the first reported association of carcinoma and factor VIII inhibitor.

Failure of factor VIII inhibitor bypassing activity (Feiba) to secure haemostasis in haemophilic patients with antibodies.

Factor IX concentrates have been widely advocated in the treatment of haemophilic patients with factor VIII inhibitors. Five such patients were given the 'activated' factor IX concentrate--factor VIII inhibitor bypassing activity (Feiba)--for 14 separate bleeding episodes. In six of the episodes, including two with external blood loss, bleeding progressed in spite of treatment. In none of the other eight episodes was there a prompt response, and it was not possible to ascribe a definite therapeutic effect.

Isoferritins in acute leukaemia.

Leucocytes containing a high proportion of blast cells were obtained from 11 patients with acute myeloid leukaemia, and leucocytes were also obtained from 2 normal subjects. Ferritin was partially purified from leucocyte extracts and subjected to anion-exchange chromatography and isoelectric focusing. The Fe content of leucocyte ferritin was low, and in all but one case the preparations contained isoferritins corresponding to those found in normal tissues or serum. Only some of the preparations contained the relatively acidic isoferritins which have been described as "carcinofoetal", but which are also present in normal heart and kidney. Ferritin from one patient contained isoferritins of lower isoelectric point than heart ferritin. These results show that there does not appear to be any specific isoelectric focusing pattern for leukaemic cells, and that assays for acidic isoferritins are unlikely to be of use in the diagnosis of leukaemia and in monitoring treatment. However, the very acidic protein found in one preparation suggests that the search for abnormal subunits of ferritin may be fruitful in acute leukaemia.

Serum ferritin in acute leukaemia at presentation and during remission.

In patients with acute myeloblastic leukaemia the mean serum ferritin concentration showed a twenty-five-fold increase compared with normal people, and in children with acute lymphoblastic leukaemia (A.L.L.) there was a thirteen-fold increase. The high concentration of circulating ferritin seemed to be related to increased synthesis by leukaemic cells. The return of serum concentrations to normal in A.L.L. patients after successful chemotherapy suggested that ferritin concentration may be a useful index of active disease and may help in prognosis.

Coma associated with vincristine therapy.

Three cases of coma after vincristine therapy are described. One patient had hyponatraemia and other features of inappropriate secretion of antidiuretic hormone. The effects were temporary, and full recovery occurred in all three patients.