Effects of skeletal muscle protein phosphatase inhibitor-2 on protein synthesis and protein phosphorylation in rabbit reticulocyte lysates

Reticulocyte lysates contain two major classes of protein phosphatase activities, designated type 1 and type 2. These designations are based on criteria derived from the analyses of protein phosphatase species in other tissues. The criteria include (i) chromatographic elution profiles on DEAE-cellulose; (ii) specificity of lysate phosphatases toward [(32)P]phosphorylase a and [(32)P]phosphorylase kinase; (iii) sensitivity of lysate phosphatases to Mg(2+) ATP; and (iv) sensitivity to the heat-stable protein phosphatase inhibitor-2. The lysate phosphatase species are similar to those described in rabbit skeletal muscle and rabbit liver. Reticulocyte protein phosphatase type 1, but not type 2, is inhibited by heat-stable protein phosphatase inhibitor-1 and -2 which have been characterized from rabbit skeletal muscle. We have initiated a study on the function and specificity of lysate protein phosphatase activities involved in the regulation of protein synthesis by examining the effects of protein phosphatase inhibitor-2 on reticulocyte protein synthesis and protein phosphorylation. Our findings are as follows. (a) Protein phosphatase inhibitor-2 inhibits protein chain initiation in hemin-supplemented lysates. (b) Inhibition is characterized by biphasic kinetics and is reversed by the delayed addition of purified reticulocyte eukaryotic initiation factor 2 (eIF-2). (c) Inhibition of protein synthesis by inhibitor-2 is accompanied by the phosphorylation of the alpha-subunit (38,000 daltons) of eIF-2 (eIF-2alpha) and of two heat-stable polypeptides of 29,000 and 44,000 daltons. (d) The 29,000-dalton component is phosphorylated in lysates under conditions of protein synthesis and appears to be inhibitor-2, but the physiological significance of this modification of inhibitor-2 is not clear. (e) Inhibitor-2 has no effect on the activation in vitro of isolated heme-regulated or double-stranded RNA-dependent eIF-2alpha kinases. We propose that the inhibition of protein synthesis in hemin-supplemented lysates by added inhibitor-2 is due at least in part to the inhibition of a type 1 eIF-2alpha phosphatase activity, which permits a basal eIF-2alpha kinase activity to be expressed leading to the accumulation of phosphorylated eIF-2alpha and an inhibition of protein synthesis.     

Effects of sustained isometric handgrip on praecordial accelerocardiogram in normal subjects and in patients with heart disease.

The effects of isometric exercise on the maximum amplitude of the praecordial accelerocardiogram (as represented by the DE deflection) have been compared in 6 normal subjects (group 1), 12 patients with aortic stenosis (group 2), and 16 patients with myocardial disease (group 3). Whereas the tachycardia and pressor effects of isometric exercise were identical in all three groups, the normal subjects showed a significant decrease in DE during handgrip of 10 +/- 4 per cent (P less than 0.05) as compared with the insignificant increases of 8.5 +/- 6 per cent (P greater than 0.5), and 4 +/- 3.5 per cent (P greater 0.3) observed in the patients in groups 2 and 3. This response in the normal subjects differed significantly from the responses observed in the patients in groups 2 (P less than 0.02) and 3 (P less than 0.01). Of the patients in each of groups 2 and 3, 50 per cent responded abnormally to handgrip in that they showed a significant increase in DE. In the patients with aortic stenosis this subgroup of patients differed from the remainder in that they had a higher resting cardiac index (P less than 0.05). In the patients with myocardial disease this subgroup was characterized by a significantly lower resting left ventricular end-diastolic pressure (P less than 0.02). It seems, therefore, that those patients who increase DE in response to handgrip tend to have better left ventricular function at rest than those who do not. We suggest that this may be because of increased beta adrenergic activity at rest and during isometric exercise in the subgroup who respond to handgrip with an increase in DE.     

Evaluation of area-based collagen scoring by nonlinear microscopy in chronic hepatitis C-induced liver fibrosis

In this paper we analyze a fibrosis scoring method based on measurement of the fibrillar collagen area from second harmonic generation (SHG) microscopy images of unstained histological slices from human liver biopsies. The study is conducted on a cohort of one hundred chronic hepatitis C patients with intermediate to strong Metavir and Ishak stages of liver fibrosis. We highlight a key parameter of our scoring method to discriminate between high and low fibrosis stages. Moreover, according to the intensity histograms of the SHG images and simple mathematical arguments, we show that our area-based method is equivalent to an intensity-based method, despite saturation of the images. Finally we propose an improvement of our scoring method using very simple image processing tools.OCIS codes: (180.4315) Nonlinear microscopy, (170.1610) Clinical applications, (170.3880) Medical and biological imaging, (170.4580) Optical diagnostics for medicine, (110.2960) Image analysis     

Multiple colonic polyps of leukemic origin

Summary and Conclusions Polyps of the colon of leukemic origin are composed purely of leukemic tissue and are caused by the leukemic disease. They are unlike pre-existing adenomatous polyps of the colon, which are invaded secondarily by leukemic cells (Fig. 6). Roentgenologic features of leukemic polyps are not identical to those of polypoid disease of the colon, yet they are sufficiently similar to require that the two conditions be differentiated carefully. One of the cases herein described was myelogenous in type and this is contrary to the statement made by Pearson that only in lymphatic leukemia do colonic lesions occur. Read at the meeting of the American Proctologic Society, Houston, Texas, April 25 to 27, 1960. Dr. Chapman is Director of Laboratories at this institute.     

Improving awareness,accountability, and access through health coaching: Qualitative study of patients’ perspectives

Objective

To assess patients’ experiences with and perceptions of health coaching as part of their ongoing care.

Design

A qualitative research design using semistructured interviews that were recorded and transcribed verbatim.

Setting

Ottawa, Ont.

Participants

Eleven patients (> 18 years of age) enrolled in a health coaching pilot program who were at risk of or diagnosed with type 2 diabetes.

Methods

Patients’ perspectives were assessed with semistructured interviews. Interviews were conducted with 11 patients at the end of the pilot program, using a stratified sampling approach to ensure maximum variation.

Main findings

All patients found the overall experience with the health coaching program to be positive. Patients believed the health coaching program was effective in increasing awareness of how diabetes affected their bodies and health, in building accountability for their health-related actions, and in improving access to care and other health resources.

Conclusion

Patients perceive one-on-one health coaching as an acceptable intervention in their ongoing care. Patients enrolled in the health coaching pilot program believed that there was an improvement in access to care, health literacy, and accountability, all factors considered to be precursors to behavioural change.     

Reasons for nonuse of antiviral treatment in patients with chronic hepatitis C infection and thrombocytopaenia: a retrospective chart review from five European countries

Antiviral therapy has been shown to reduce the risk of disease progression, liver damage and death in patients with chronic hepatitis C virus (HCV) infection. While interferon labels recommend that patients with platelet counts below 50 × 10³/μL not receive interferon‐based therapy, it is unknown to what extent thrombocytopaenia influences treatment decisions in practice. This study profiles the reasons for withholding antiviral treatment in HCV patients with thrombocytopaenia in five European countries. Medical records of 466 patients who had HCV infection and thrombocytopaenia (platelet count <100 × 10³/μL) in 2006 were retrospectively reviewed for clinical characteristics. Collected data included use of antiviral therapy and reasons for withholding therapy. In total 184 of 466 patients (39.5%) did not receive interferon‐based therapy during the study period, with treatment withheld most frequently due to multiple clinical characteristics including hepatic cirrhosis (16.3%), thrombocytopaenia (16.3%) and age >60 years (10.9%). The reasons for lack of treatment varied among countries, with thrombocytopaenia as a reason being more common in Italy (10.9%) and Spain (20.0%), and less common in France, Germany and the UK (3.2–7.1%). Overall, thrombocytopaenia was reported as the only reason for withholding treatment in 4.9% of untreated patients. This study demonstrates that thrombocytopaenia is one of many factors, indicative of the poor clinical state of the patient, that contributes to withholding antiviral treatment. In 4.9% of untreated patients, thrombocytopaenia can be considered as a modifiable factor to enable more HCV patients to receive guideline‐recommended therapy and thus improved clinical outcomes.     

Health impacts of bushfire smoke exposure in Australia

Smoke exposure from bushfires, such as those experienced in Australia during 2019–2020, can reach levels up to 10 times those deemed hazardous. Short‐term and extended exposure to high levels of air pollution can be associated with adverse health effects, although the most recent fires have brought into sharp focus that several important knowledge gaps remain. In this article, we briefly identify and discuss the existing Australian evidence base and make suggestions for future research.