Isoleucine metabolism by leukemic and normal human leukocytes in relation to cell maturity and type

The metabolism of an essential amino acid, isoleucine, by human leukemic and gradient-separated normal human leukocytes of various types and maturity was studied. Blood leukocytes were isolated and incubated with (U-14C) isoleucine. Separation of metabolic intermediates was accomplished by sequential extraction. The rate of isoleucine incorporation into protein by immature cells from untreated patients with acute leukemia (15.9 plus or minus 2.4 nmoles/hr per 10-8 leukocytes) was considerably higher than the rates of incorporation by mature neutrophils (3.2 plus or minus 0.5 nmoles/hr per 10-8 leukocytes), lymphocytes (7.7 plus or minus 1.2 nmoles/hr per 10-8 leukocytes), and eosinophils (6.2 plus or minus 1.3 nmoles/hr per 10-8 leukocytes). Those cell preparations with more blast cells had higher rates of protein synthesis. In addition, those cells with greater thymidine incorporation had higher rates of protein synthesis. The leukocytes both oxidized isoleucine and incorporated it into cell isoleucine and incorporated it into cell lipid. The rates of these metabolic processes were characteristic for various types and maturity of leukocytes. This study demonstrates a relationship of rate of protein synthesis to leukocyte immaturity. This relationship is maintained in neoplastic leukocytes. It suggests that the requirement of the mitotic process for newly synthesized protein is greater than that for the elaboration of the protein products of the mature leukocyte.     

Multiple sclerosis with clinical and radiological features of cerebral tumour

Three cases of multiple sclerosis, all confirmed pathologically, are described in whom both the unusual clinical features and the CT scan appearances suggested cerebral tumours. The failure of mass effect reliably to differentiate plaques and tumours on a CT scan is stressed and the literature relating to CT scanning in multiple sclerosis is reviewed.     

Proctalgia Fugax in Patients with the Irritable Bowel, Peptic Ulcer, or Inflammatory Bowel Disease

One hundred forty-eight patients with gastrointestinal disease, 50 patients with the irritable bowel syndrome (IBS) and 49 each with peptic ulcer and inflammatory bowel disease, were interviewed to determine if they had proctalgia fugax (PF) and if the symptom was associated with the IBS. One-third of the patients had PF. It occurred in 51% of females and 12% of males (p less than 0.001). When corrected for sex, PF was no more prevalent in IBS than in peptic ulcer or inflammatory bowel disease. Only two of six previously described IBS symptoms were more prevalent in the PF patients. Attacks occurred in the day in 94%, and one-third of sufferers related them to defecation. The pain was localized in the anus in 90%, occurred less than five times a year in 51%, and lasted less than 1 min in 57%. In most, activity was not interrupted by this pain and only 20% had ever reported it to a physician. PF is very common among patients with abdominal symptoms, but is not related to the IBS. Since it is infrequent, benign, and transient, PF is usually not mentioned to the physician.     

Preferences for rehabilitation services among women with major limb amputations

Purpose

We present five cases of adult females with major limb amputations, their concerns and preferences for services across the life span.

Design

A convenience sample of five veteran and nonveteran women aged 19–58 with major limb amputations participating in a regional VA Prosthetics Conference in 2010 took part in a panel interview.

Findings

The concerns identified by these women as high priorities included independence and participation in a full range of life activities, limitations in access, patient decision‐making and body image concerns, and preferences for selected services. Maximizing function and quality of life for women amputees requires identifying patient preferences for rehabilitation and prosthetic services. Lessons learned could inform development of clinic‐based rehabilitation care, prosthetic services, and studies of women with major limb amputations.

Conclusions

As the current conflicts in Iraq and Afghanistan wind down, the number of women veterans seeking rehabilitation and prosthetic services will increase. With this information, rehabilitation and prosthetic service providers and organizations will be uniquely positioned to provide prevention and treatment of amputations for this growing population of women veterans in national care delivery systems and in communities.

Clinical Relevance

An open‐ended facilitated discussion among a panel of women with major limb amputations provided insights for providers and organizations with respect to needs, concerns, and preferences for rehabilitation and prosthetic services.     

Vascular endothelial growth factor (VEGF) and VEGF receptor expression in biopsy samples of liver from dogs with congenital portosystemic shunts

Surgical attenuation of a congenital portosystemic shunt (CPSS) results in increased liver mass, development of intrahepatic portal vasculature and improved liver function. Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. The aim of this study was to investigate the role of VEGF and its receptor in the hepatic response to CPSS surgery. The study included 99 dogs with CPSS treated with either partial or complete suture attenuation. Forty-four dogs with partial attenuation underwent a second surgery for complete attenuation. The expression of VEGF and VEGF receptor 2 (VEGFR2) in biopsy samples of liver was assessed by immunohistochemistry with rabbit anti-human VEGF polyclonal antibody and mouse anti-human VEGFR2 monoclonal antibody. Expression of these molecules was graded. The proportion of samples expressing VEGF was significantly greater in samples from dogs with CPSS compared with control samples (P=0.04) and the proportion of samples expressing VEGFR2 was significantly greater in control samples compared with samples from dogs with CPSS (P=0.04). VEGF labelling grade decreased significantly (P=0.038) and VEGFR2 increased significantly (P=0.046) between first and second surgery. The decrease in VEGF may reflect transient expression, preferential expression of other factors, reperfusion of existing vessels and/or increased angiogenesis before surgery in the form of arterialization and subsequent reduction due to improved portal blood flow. Partial suture attenuation was associated with a degree of 'normalization' of VEGF and VEGFR2 expression when compared with the control samples. Further investigation is needed to provide more information on the hepatic response to CPSS surgery.     

Regulation of endothelial prostacyclin synthesis by protease-activated receptors: mechanisms and significance

The cellular actions of serine proteases are mediated through activation of a novel family of four G protein-coupled receptors known as protease-activated receptors (PARs). PARs are emerging as important modulators of diverse biological functions and there is evidence supporting roles for these receptors in both physiological and pathological settings in the cardiovascular system. Endothelial cells express all four known PARs but their specific roles as modulators of endothelial cell function are not well understood. One physiologically important response of the endothelium to PAR stimulation is the generation of prostacyclin (PGI(2)) through cyclooxygenase (COX)-dependent pathways. Our studies have used selective PAR-activating peptides, endogenous PAR agonists, and pharmacological and molecular approaches to identify the mechanisms coupling PARs activation with endothelial PGI(2) synthesis and release, These mechanisms are differentially recruited by individual PARs but activation of the ERK1/2 and p38 families of mitogen-activated protein kinases (MAPK), as well as the nuclear factor kappa-B (NF-kappaB) pathway, play significant roles in controlling PAR-induced prostanoid formation through regulation of COX-2 induction and cytosolic phospholipase A(2)alpha (cPLA(2)alpha) activation. PAR agonists also modulate PAR expression by mechanisms that require p38(mapk) as well as NF-kappaB. The defensive actions of PGI(2) in the vascular wall are well-established, and the ability of PARs to drive acute and chronic synthesis of this mediator suggests a potential role for these receptors in vascular protection. Our findings therefore have important implications for defining the vascular effects of current and future therapeutic agents that target COXs, PARs, and the signalling elements controlling their expression.     

Bone-marrow microinvolvement in non-small cell lung cancer is not a reliable indicator of tumour recurrence and prognosis.

AIMS: This study aimed to examine the incidence of bone-marrow microinvolvement in non-small cell lung cancer (NSCLC) patients and its correlation with tumour recurrence and prognosis. METHODS: Between March 1997 and August 1998, we analysed 96 bone-marrow specimens (from the posterior iliac crest) of NSCLC patients before surgery. Tumour differentiation showed well differentiated carcinoma in six, moderately differentiated carcinoma in 69, and poorly differentiated carcinoma in 21. p-TNM staging showed stage Ia in five, stage Ib in 33, stage IIb in 19, stage IIIa in 26, stage IIIb in eight, and stage IV in five. The specimens were examined by immunohistochemical staining with anti-human cytokeratin AE1/AE3 and clone MNF116 mixed solution (Ab1, n=96) and/or Ber-EP4 (Ab2, n=80) to detect the presence of malignant epithelial cells in the bone marrow. RESULTS: Positive results were observed in 21 patients (21. 9%). The occurrence of bone-marrow microinvolvement was not related to patient age, sex, cell type, or TNM status. The 30-month disease-free survival rates were 50.2% and 53.9% in bone-marrow negative and bone-marrow positive patients, respectively (P=0.5670); the 30-month cumulative survival rates were 66.7% and 67.6% in bone-marrow negative and bone-marrow positive patients, respectively (P=0.9351). Multivariate analysis failed to demonstrate bone-marrow microinvolvement as an independent prognostic factor. CONCLUSIONS: Our results show that bone-marrow microinvolvement is not unusual, and its occurrence cannot be translated into early tumour recurrence or poor outcome during an intermediate-term follow-up, which means bone-marrow microinvolvement may be an epiphenomenon rather than true metastasis in NSCLC.