Inheritance of mitochondrial and chloroplast genome markers in backcrosses of Chlamydomonas eugametos x Chlamydomonas moewusii hybrids

Summary Southern blot analysis of AvaI-digested total cellular DNA from the interfertile species Chlamydomonas eugametos and Chlamydomonas moewusii with a coxI mitochondrial gene probe from Chlamydomonas reinhardtii revealed single hybridizing fragments of 5.0 and 3.5 kb, respectively. The transmission of these mitochondrial DNA physical markers along with that of chloroplast genetic markers for resistance to streptomycin and resistance to erythromycin was studied in the fourth backcrosses of F₁ hybrids to one or the other parent. Viability in these backcrosses is high in contrast to the cross C. eugametos x C. moewusii and its reciprocal which are associated with considerable meiotic product lethality. The resulting zygospores were found to transmit the mitochondrial and chloroplast genome markers uniparentally or preferentially from the mating-type-plus parent. Thus the species pair C. eugametos and C. moewusii differs from the pair Chlamydomonas reinhardtii and Chlamydomonas smithii in which mitochondrial genome markers are transmitted uniparentally by the mating-type minus parent, while the chloroplast genome markers are transmitted uniparentally by the opposite parental mating-type (Boynton et al. 1987).     

Pharmacokinetic analysis of pegylated megakaryocyte growth and development factor in humans

Phase I studies with pegylated megakaryocyte growth and development factor (PEG-rHuMGDF), a c-Mpl ligand that stimulates megakaryopoiesis, have demonstrated that PEG-rHuMGDF is biologically active alone and causes a dose-related enhancement of platelet recovery when administered after chemotherapy. Here we report the dose-ranging pharmacokinetics of PEG-rHuMGDF. Pre-injection blood samples were drawn daily for pharmacokinetic studies on 43 patients. An ELISA, established using PEG-rHuMGDF as the standard, was able to quantitate Mpl ligand at concentrations > 0.02 ng/mL. Over the dose range 0.03 to 5.0 microg/kg/day, subcutaneous administration produced linear increases in steady-state serum levels. Maximum levels of PEG-rHuMGDF attained after 5.0 microg/kg/day were 5.88 to 10.9 ng/mL. After discontinuation of PEG-rHuMGDF, concentrations of Mpl ligand returned to baseline within 5 days. The pharmacokinetics were best described by a one-compartment model with first-order absorption, an absorption delay, and non linear clearance over the first 48 hours. The mean terminal half-life was 33.3 + 16.7 hours, and the average apparent at steady state was 27.7 + 14.0 mL/h/kg; both were independent of administered dose. The apparent clearance of PEG-rHuMGDF was not predicted by platelet count. Administration of chemotherapy and Filgrastim did not alter the pharmacokinetics of PEG-rHuMGDF.     

Regulation of T-cell function in lung tissue by pulmonary alveolar macrophages.

We have examined by limit dilution analysis the frequency of several types of DBA/2-specific precursor cells found in the draining lymph nodes of BALB/c mice following anterior chamber or subconjunctival inoculations of P815 tumour cells. Assays for precursors of cytotoxic T cells (pTc) and T-helper cells [interleukin-2 (IL-2)- and IL-4-producing cells] were conducted periodically during a 6-month interval after injection of tumour cells. The results indicate that nodes of both sets of recipients contained primed P815-specific CD8+ pTc that were detectable within 2 weeks of tumour implantation, and persisted throughout the 6-month observation period. Early after tumour inoculation, but not thereafter, these CD8+ cells also secreted Il-2. By contrast, only lymph nodes from mice that received P815 cells into the subconjunctival space contained CD4+ cells that secreted both IL-2 and IL-4; eventually, IL-4-secreting cells formed the vast majority of P815-specific CD4+ cells in these mice. Lymph nodes of mice that received P815 cells in the anterior chamber contained CD4+ T cells that were clonally expanded, and secreted IL-2, but not IL-4. These IL-2-secreting cells proved to be short-lived and were not present 6 months after inoculation. It is proposed that the IL-2- and IL-4-secreting T cells found in lymph nodes of subconjunctival tumour recipients are in vivo homologues of Th0 cells, that these cells can mediate delayed hypersensitivity responses, and that they are the forerunners of, or are themselves, memory T cells. These data indicate that the failure of mice that receive P815 tumour cells in the anterior chamber to display antigen-specific delayed hypersensitivity results from an inability to convert antigen-activated, IL-2-only-secreting CD4+ T cells (pTh) into Th0 cells. These findings also imply that mice with anterior chamber-associated immune deviation (ACAID) fail to develop memory CD4+ T cells.     

Interlimb coupling strength scales with movement amplitude

The relation between movement amplitude and the strength of interlimb interactions was examined by comparing bimanual performance at different amplitude ratios (1:2, 1:1, and 2:1). For conditions with unequal amplitudes, the arm moving at the smaller amplitude was predicted to be more strongly affected by the contralateral arm than vice versa. This prediction was based on neurophysiological considerations and the HKB model of coupled oscillators. Participants performed rhythmic bimanual forearm movements at prescribed amplitude relations. After a brief mechanical perturbation of one arm, the relaxation process back to the initial coordination pattern was examined. This analysis focused on phase adaptations in the unperturbed arm, as these reflect the degree to which the movements of this arm were affected by the coupling influences stemming from the contralateral (perturbed) arm. The thus obtained index of coupling (IC) reflected the relative contribution of the unperturbed arm to the relaxation process. As predicted IC was larger when the perturbed arm moved at a larger amplitude than did the unperturbed arm, indicating that coupling strength scaled with movement amplitude. This result was discussed in relation to previous research regarding sources of asymmetry in coupling strength and the effects of amplitude disparity on interlimb coordination.     

Involving the patient: a prospective study on use, appreciation and effectiveness of an information system in head and neck cancer care

OBJECTIVE: To determine use, appreciation and effectiveness of an electronic health information support system in head and neck (H&N) cancer care. DESIGN: A prospective evaluation study. The evaluated system has four different functions: (1) communication amongst health care providers and between health care providers and patients, (2) information for health care providers and patients, (3) contact with fellow sufferers and (4) monitoring of discharged patients by means of electronic questionnaires. Evaluation of the system was done both objectively using automatically created log files and stored messages, and subjectively by using paper questionnaires from patients and general practitioners (GPs). SETTING: Department of Otorhinolaryngology and Head and Neck Surgery of a tertiary health care centre in the Netherlands. The system was put at patients' disposal for a period of 6 weeks following discharge from the hospital after surgery for H&N cancer, and was additional to standard care. PARTICIPANTS: Head and neck cancer patients, hospital physicians, members of a hospital-based support team, GPs, district nurses and speech therapists. MAIN OUTCOME MEASURES: Actual use of the system by patients and health care providers. Patients' appreciation for each of the system's four different functions. GPs' appreciation for the system. Capability to detect potential patient problems with the system. RESULTS: The system was used by 36 H&N cancer patients, 10 hospital physicians, 2 members of the support team, 8 GPs, 2 district nurses and 2 speech therapists. The total number of patient-sessions was 982: an average of 27.3 sessions per patient during the 6 weeks study period. In total, 456 monitoring questionnaires were completed. The support team in hospital responded with 231 actions. In 16 cases, an extra appointment was made for a patient with the hospital physician. Out of these cases, immediate action was considered necessary eight times. Patients appreciated the system highly, rating it with an average score of 8.0 on a 10-point scale. All patients used the monitoring function, and rated 'monitoring' with a mean score of 8.0 on a 10-point scale. Least used and appreciated was the 'contact with fellow sufferers' function. Only 8 out of possible 36 GPs used the system, rating it with an average of 5.6 on a 10-point scale. CONCLUSIONS: The electronic health information support system was used intensively and highly appreciated by H&N cancer patients. The system enabled the early detection of occurring health problems that required direct intervention. ICT can play an additional role in the management of patients, also in a relatively elderly and computer illiterate patient population.     

Cloning and functional characterization of a novel connexin expressed in somites of Xenopus laevis.

Connexin-containing gap junctions play an essential role in vertebrate development. More than 20 connexin isoforms have been identified in mammals. However, the number identified in Xenopus trails with only six isoforms described. Here, identification of a new connexin isoform from Xenopus laevis is described. Connexin40.4 was found by screening expressed sequence tag databases and carrying out polymerase chain reaction on genomic DNA. This new connexin has limited amino acid identity with mammalian (<50%) connexins, but conservation is higher (approximately 62%) with fish. During Xenopus laevis development, connexin40.4 was first expressed after the mid-blastula transition. There was prominent expression in the presomitic paraxial mesoderm and later in the developing somites. In adult frogs, expression was detected in kidney and stomach as well as in brain, heart, and skeletal muscle. Ectopic expression of connexin40.4 in HEK293 cells, resulted in formation of gap junction like structures at the cell interfaces. Similar ectopic expression in neural N2A cells resulted in functional electrical coupling, displaying mild, asymmetric voltage dependence. We thus cloned a novel connexin from Xenopus laevis, strongly expressed in developing somites, with no apparent orthologue in mammals.     

Regulation of T-cell activation in the lung: alveolar macrophages induce reversible T-cell anergy in vitro associated with inhibition of interleukin-2 receptor signal transduction.

Alveolar macrophages (AM) are recognized as archetypal 'activated' macrophages with respect to their capacity to suppress T-cell responses to antigen or mitogen, and this function has been ascribed an important role in the maintenance of local immunological homeostasis at the delicate blood:air interface. The present study demonstrates that this suppression involves a unique form of T-cell anergy, in which 'AM-suppressed' T cells proceed normally through virtually all phases of the activation sequence including Ca2+ flux, T-cell receptor (TCR) modulation, cytokine [including interleukin-2 (IL-2)] secretion and IL-2 receptor (IL-2R) expression. However, the 'suppressed' T cells fail to up-regulate CD2, and do not re-express normal levels of TCR-associated molecules after initial down-modulation; moreover, they are unable to transduce IL-2 signals leading to phosphorylation of IL-2R-associated proteins, and remained locked in G0/G1. The induction of this form of anergy is blocked by an NO-synthase inhibitor, and is reversible upon removal of AM from the T cells, which then proliferate in the absence of further stimulation. We hypothesize that this mechanism provides the means to limit the magnitude of local immune responses in this fragile tissue microenvironment, while preserving the capacity for generation of immunological memory against locally encountered antigens via clonal expansion of activated T cells after their subsequent migration to regional lymphoid organs. In an accompanying paper, we demonstrate that a significant proportion of T cells freshly isolated from lung exhibit a comparable surface phenotype.     

Subacute thyroiditis (de Quervain) presenting as a painless "cold" nodule

A 49-yr-old woman presented with a solid, painless, nontender nodule in the left thyroid lobe. Thyroid scintigraphy revealed a solitary "cold" area in the left lobe and a slightly decreased 24-hr radioactive iodine thyroid uptake (9%). Although there were no specific clinical or biochemical signs suggesting thyroiditis needle aspiration cytology showed the presence of a subacute thyroiditis. Approximately 1 mo later the entire thyroid gland was affected leading to a completely suppressed thyroid radioiodine uptake and elevated serum thyroid hormone concentrations. This case illustrates that in the early phase of the disease, subacute thyroiditis may present as a solitary, painless, "cold" nodule and should be considered in the differential diagnosis of such lesions.     

Anastomotic insufficiency in small bowel surgery —incidence and treatment

Summary In the period 1977–1981 234 small bowel anastomoses were constructed in 143 patients. Eight anastomoses showed leakage (3.4%) and from nine anastomoses a fistula developed (3.8%): a total rate of disturbed healing of small bowel anastomoses (7.3%). In the presence of intra-abdominal infection this rate was 14.8%, in the absence of infection 0.8%. The results of treatment with oversewing and with resection and immediate anastomosis were disappointing. Better results were obtained by dismantling of the anastomosis, establishment of a split-enterostomy and reestablishment of continuity in a second stage. Mortality was 3/17 (18%). The literature is reviewed.

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Insuffizienz von Dünndarmanastomosen — Ineidenz und Therapie

Zusammenfassung In dem Zeitraum 1977–1981 wurden bei 143 Patienten 234 Dünndarmanastomosen angelegt. Acht Anastomosen zeigten eine Nahtleckage (3,4%), bei neun entwickelte sich eine Fistel (3,8%): die Gesamthäufigkeit von Wundheilungsstörungen bei Dünndarmanastomosen war 7,3%. Bei gleichzeitigem Vorliegen intraabdominaler Infektionen betrug die Häufigkeit 14,8%, ohne diese 0,8%. Die Resultate einer Therapie durch Übernähung oder Resektion mit sofort anschließender Reanastomosierung waren enttäuschend. Befriedigendere Ergebnisse wurden durch Aufheben der Anastomosen, Anlage einer split enterostomy unter Wiederherstellung der Kontinuität in einer zweiten Sitzung erzielt. Die Mortalität betrug 3/17 (18%). Ein Literaturüberblick wird gegeben.