Genotype-limited changes in platelet and erythroid kinetics in Friend-virus-infected allophenic mice

We report here results suggesting that cells of the megakaryocytic lineage or uncommitted precursor cells may be targets for Friend-virus-induced proliferation, and that genetic differences (other than Fv-2) between strains C57BL/6 and DBA/2 affect the susceptibility of these cells to Friend virus. The evidence suggesting this was derived from experiments with C57BL/6 in equilibrium DBA/2 allophenic mice. Within the first few weeks following infection of these mice with the polycythemic NB-tropic strain of Friend virus (FV-P), we observed a rapid shift in the genotypic composition of both red cells and platelets in favor of those of the DBA/2 genotype. Infection with the anemia-inducing strain of Friend virus (FV-A) also resulted in preferential production of DBA/2 strain erythrocytes, but its effect on platelet kinetics was nil. The FV-P- and FV-A-induced change in red cell composition is consistent with the view that erythroid precursors are target cells for Friend virus and that viral infection preferentially stimulates proliferation of susceptible strain (DBA/2) erythroid precursors. As for the platelet shifts induced by FV-P (and not FV-A), we believe the changes in platelet mosaicism also could be caused by viral-induced proliferation of DBA/2 platelet precursors, or more primitive progenitors, over the C57BL/6 ones. Thus, these results implicate the existence of nonerythroid target cells for FV-P-induced proliferation, as well as the existence of genetic differences between strains C57BL/6 and DBA/2 that modulate the responsiveness of such cells to infection.     

Prolonged stimulation of respiration by endogenous central serotonin

We have recently reported a new neural brainstem mechanism which is uniquely activated by stimulation of carotid body afferent input to the brain and which facilitates respiration for hours after the immediate affects of the stimulation have dissipated (Millhorn, Eldridge and Waldrop, 1980). In the present study respiratory responses to carotid body or carotid sinus nerve stimulation were measured in vagotomized, anesthetized, and paralyzed cats whose end-tidal PCO2 and temperature were servo-controlled and kept constant. The responses of animals pretreated with various serotonin antagonists and a dopamine-norepinephrine antagonist were compared to the responses of untreated control animals. All three differently acting serotonin antagonists (methysergide, parachlorophenylalanine, and 5, 7-dihydroxytryptamine) either prevented or significantly reduced the magnitude of the long-lasting respiratory response whereas the dopamine-norepinephrine antagonist (alpha-methyltyrosine) failed to alter it. We conclude that the long-lasting increase of respiratory activity following stimulation of carotid body afferents is due to activation of an endogenous central serotoninergic mechanism which facilitates respiration.     

New evidence for,and challenges in,linking small CGG repeat expansion FMR1 alleles with Parkinson's disease

We recently reported a significant increase in the frequency of carriers of grey zone (GZ) alleles of FMR1 gene in Australian males with Parkinson's disease (PD) from Victoria and Tasmania. Here, we report data comparing an independent sample of 817 PD patients from Queensland to 1078 consecutive Australian male newborns from Victoria. We confirmed the earlier finding by observing a significant excess of GZ alleles in PD (4.8%) compared to controls (1.5%). Although both studies provided evidence in support of an association between GZ‐carrier status and increased risk for parkinsonism, the existing evidence in the literature from screening studies remains equivocal and we discuss the need for alternative approaches to resolve the issue.     

Lessons from joint development for cartilage repair in the clinic

More than 250 years ago, William Hunter stated that when cartilage is destroyed it never recovers. In the last 20 years, the understanding of the mechanisms that lead to joint formation and the knowledge that some of these mechanisms are reactivated in the homeostatic responses of cartilage to injury has offered an unprecedented therapeutic opportunity to achieve cartilage regeneration. Very large investments in ambitious clinical trials are finally revealing that, although we do not have perfect medicines yet, disease modification is a feasible possibility for human osteoarthritis.     

Characterization of poly-4-hydroxybutyrate mesh for hernia repair applications

Background

Phasix mesh is a fully resorbable implant for soft tissue reconstruction made from knitted poly-4-hydroxybutyrate monofilament fibers. The objectives of this study were to characterize the in vitro and in vivo mechanical and resorption properties of Phasix mesh over time, and to assess the functional performance in a porcine model of abdominal hernia repair.

Materials and methods

We evaluated accelerated in vitro degradation of Phasix mesh in 3 mol/L HCl through 120 h incubation. We also evaluated functional performance after repair of a surgically created abdominal hernia defect in a porcine model through 72 wk. Mechanical and molecular weight (MW) properties were fully characterized in both studies over time.

Results

Phasix mesh demonstrated a significant reduction in mechanical strength and MW over 120 h in the accelerated degradation in vitro test. In vivo, the Phasix mesh repair demonstrated 80%, 65%, 58%, 37%, and 18% greater strength, compared with native abdominal wall at 8, 16, 32, and 48 wk post-implantation, respectively, and comparable repair strength at 72 wk post-implantation despite a significant reduction in mesh MW over time.

Conclusions

Both in vitro and in vivo data suggest that Phasix mesh provides a durable scaffold for mechanical reinforcement of soft tissue. Furthermore, a Phasix mesh surgical defect repair in a large animal model demonstrated successful transfer of load bearing from the mesh to the repaired abdominal wall, thereby successfully returning the mechanical properties of repaired host tissue to its native state over an extended time period.     

Returning to work with aphasia: A case study

Background: For some people with aphasia, returning to work will be their eventual goal. While there are reports in the literature of incidence of return to work, and general discussion of success, there are few documented in depth studies of what this might entail for the individual with aphasia.

Aims: This paper explores returning to work with aphasia, and examines the complex relationship between the person, the aphasia and the demands of employment.

Methods & Procedures: This is a detailed case report, describing and reflecting on the experiences of GD, who returned to work following his stroke and aphasia. Therapy focused specifically on work requirements is described and the factors affecting GD's return to work explored. An interview was used to elicit GD's reflections on his experiences.

Outcome & Results: GD's language skills improved over time and with therapy, and he developed several strategies that facilitated his communication. He was able to return to work (part-time) in a modified role and this was successful initially. After an extended period (～19 months) his employment was terminated and GD explored other options. He moved on to a volunteering and charity trustee role.

Conclusions: The success (or not) of returning to work with aphasia is multi-faceted and does not rest solely with the person with aphasia. The nature of the work may have a strong bearing on success, as will the ability and willingness of the employer to engage in the process. Partnership with the person and constant review of goals and management is of overwhelming importance. We need to consider what “success” may mean in this context and the need to consider therapeutic and rehabilitation needs over a longer time frame.     

Detection of anti-HTLV-I Tax antibodies in HTLV-I enzyme-linked immunosorbent assay-negative individuals

The HTLV-I tax gene protein (Tax) is not packaged within the mature viral particle from which the proteins for the commercially available enzyme-linked immunosorbent assay (ELISA) are derived. Screening of 162 individuals within a cohort of white intravenous (IV) drug abusers, previously identified as having an increased incidence of HTLV-I infection, demonstrated that seven of them had antibodies to the HTLV-I Tax protein but tested negative in HTLV-I ELISAs and Western blots prepared from purified virion proteins. Three out of 35 individuals in other behaviorally defined high-risk groups also displayed this limited pattern of reactivity to HTLV-I proteins. The presence of the anti-HTLV- I p40/Tax antibodies was determined by radioimmunoprecipitation assay (RIPA), which also revealed low levels of anti-env reactivity. The specificity of the anti-p40 reactivity was confirmed on specific Tax ELISAs and Western blots prepared from recombinantly produced Tax. In vitro gene amplification by the polymerase chain reaction (PCR) was used to establish the presence of sequences homologous to HTLV-I proviral DNA in four/four of these HTLV-I ELISA negative, Tax ELISA/Tax western blot/RIPA positive individuals. These data suggest that the true incidence of HTLV-I infection within high-risk cohorts is greater than previously reported.     

Aerobic responses to low level exercise testing following an acute myocardial infarction

Thirty-four patients who had recently sustained an acute myocardial infarction performed low-level exercise testing with analysis of expired gas 7.1 +/- 2.6 days after the event. They were classified as finishers (F) and nonfinishers (NF) of the low-level protocol. The ejection fraction in the NF was 39 +/- 14% vs 56 +/- 17% in the F (p less than 0.01), and the NF had 2.6 +/- 0.8 vessels stenosed vs 1.8 +/- 0.9 vessels stenosed in the F (p less than .05). Ten normal subjects also performed the exercise test. At the same workload, patients with recent myocardial infarction had significantly lower oxygen consumption (NF less than F), significantly higher minute ventilation (NF greater than F), ventilatory equivalent for oxygen (NF greater than F), and higher respiratory exchange ratio (NF greater than F) than did normal subjects. The heart rate responses were higher in the post infarction patients than in normal subjects. The oxygen pulse was significantly lower in the cardiac patients compared to normals. These findings suggest that during the early recovery phase from an acute myocardial infarction, patients, particularly the NF, utilize less oxygen at submaximal work loads than do normal subjects. This suggests that in these patients part of the energy requirements for exercise are met anaerobically. This could be due to abnormal extraction of oxygen by the working muscles or as a result of poor delivery of oxygen due to abnormal left ventricular function.