Structural analysis and fatty acid-binding properties of two Croatian variants of human serum albumin

BACKGROUND: The aim of the present work was to characterize the molecular defects of a slow-migrating (albumin Zagreb) and a fast-migrating (albumin Krapina) genetic variant of human serum albumin detected in heterozygous persons living in Croatia and to elucidate the fatty acid-binding properties of the two alloalbumins. METHODS: Purification and structural identification of the variants were performed by conventional protein chemistry methods, whereas types and amounts of albumin-bound, endogenous fatty acids were determined by gas chromatography. RESULTS: Protein sequencing established that albumin Zagreb is a proalbumin variant (-1Arg-->Gln), and that albumin Krapina is due to a mutation within the mature polypeptide chain (573Lys-->Glu). The gas chromatographic results showed that the fatty acid-binding properties of the proalbumin variant are normal, while the amino acid substitution in position 573 resulted in a general decrease of fatty acid binding. CONCLUSIONS: The structural defects of the first alloalbumins, detected by routine clinical electrophoresis among the Croatian population, were characterized. Albumin Zagreb is caused by a hot-spot mutation occurring in a CpG sequence in the albumin gene. It is commonly assumed that bisalbuminaemia has no direct clinical relevance. However, the present study suggests that naturally occurring mutations can affect the ligand-binding properties of human serum albumin.     

Medroxyprogesterone and conjugated oestrogen are equivalent for hot flushes: a 1-year randomized double-blind trial following premenopausal ovariectomy

Oestrogen therapy is the gold standard treatment for hot flushes/night sweats, but it and oestrogen/progestin are not suitable for all women. MPA (medroxyprogesterone acetate) reduces hot flushes, but its effectiveness compared with oestrogen is unknown. In the present study, oral oestrogen [CEE (conjugated equine oestrogen)] and MPA were compared for their effects on hot flushes in a planned analysis of a secondary outcome for a 1-year randomized double-blind parallel group controlled trial in an urban academic medical centre. Participants were healthy menstruating women prior to hysterectomy/ovariectomy for benign disease. A total of 41 women {age, 45 (5) years [value is mean (S.D.)]} were enrolled; 38 women were included in this analysis of daily identical capsules containing CEE (0.6 mg/day) or MPA (10 mg/day). Demographic variables did not differ at baseline. Daily data provided the number of night and day flushes compared by group. The vasomotor symptom day-to-day intensity change was assessed by therapy assignment. Hot flushes/night sweats were well controlled in both groups, one occurred on average every third day and every fourth night. Mean/day daytime occurrences were 0.363 and 0.187 with CEE and MPA respectively, but were not significantly different (P=0.156). Night sweats also did not differ significantly (P=0.766). Therapies were statistically equivalent (within one event/24 h) in the control of vasomotor symptoms. Day-to-day hot flush intensity decreased with MPA and tended to remain stable with CEE (P<0.001). In conclusion, this analysis demonstrates that MPA and CEE are equivalent and effective in the control of the number of hot flushes/night sweats immediately following premenopausal ovariectomy.     

Arterial concentration of 99mTc-sestamibi at rest, during peak exercise and after dipyridamole infusion

Tracers for myocardial perfusion imaging during stress should not only have high cardiac uptake but they should also have a fast blood clearance to prevent myocardial tracer uptake after the ischaemic stimulus. The present study characterize the early phase of the arterial (99m)Tc-sestamibi (MIBI) time-activity curve after venous bolus injection at rest, during peak exercise and after dipyridamole infusion. We included 11 patients undergoing angioplasty for one-vessel disease (rest study) and 20 patients evaluated for the detection of haemodynamic significant coronary stenoses by (99m)Tc-sestamibi single photon emission computed tomography (SPECT) using either bicycle exercise testing (10 patients) or standard dipyridamole testing (10 patients). Arterial blood samples of 1 ml were taken from the left femoral artery (rest study) or the right radial artery (exercise and dipyridamole studies) every 5 s during the first 5 min postinjection. In the exercise and the dipyridamole studies blood sampling were extended to include blood samples every 5 min 5-30 min postinjection. Peak MIBI concentration was lower and decrease in concentration slower after tracer injection during exercise than during dipyridamole stress testing. This may cause an underestimation of perfusion defects during exercise because of MIBI uptake after the ischaemic stimulus. The implications of the study not only refer to the choice of stress modality when using MIBI. This study also underlines the importance of considering early blood clearance in addition to regional myocardial tracerkinetic aspects such as myocardial extraction fraction when new tracers are introduced.     

Amino acid substitutions in the melanoma antigen recognized by T cell 1 peptide modulate cytokine responses in melanoma-specific T cells

Single amino acid substitutions in melanoma-associated peptides dramatically enhance T-cell cytotoxicity against target cells presenting the modified peptides (often referred to as heteroclitic peptides). The authors tried to determine whether peptide modifications influence other aspects of T-cell immunity toward malignant melanoma. A heteroclitic peptide, E26F, with an E to F substitution in melanoma antigen recognized by T cell 1 (MART-1)26-35, triggers an enhanced tyrosine phosphorylation response when compared with the native- and other-modified MART-1 peptides. Similarly, the E26F peptide enhances the production of mRNA for interleukin (IL)-5, IL-10, IL-13, IL-15, and interferon-gamma and significantly enhances release of IL-13 and IL-10 from anti-MART-1 cytotoxic T cells. Another heteroclitic peptide, 1L, with an A to L substitution in MART-1(27-35), also enhances the tyrosine phosphorylation response in anti-MART-1 cytotoxic CD8+ T cells. Yet, 1L does not enhance the production of T helper cell type 2-like cytokines (IL-10 and IL-13). Together these data show that minor amino acid modifications of immunodominant melanoma peptides profoundly influence the cytokine response in melanoma-specific T cells.     

The influence of sex and pre-traumatic headache on the incidence and severity of headache after head injury

Pre- and post-traumatic headache of 168 individuals aged 18-60 years was registered 9-12 months after a head trauma. Headache before the trauma was reported by 39.9%, women being in the majority. After the trauma 64.3% were suffering from headache. Post-traumatic headache was reported by 64 patients (38.1%), of whom 22 patients experienced an increase of already existing headache and 42 patients complained of new headache. Patients suffering from headache before the trauma were not more at risk of having post-traumatic headache than patients who did not suffer from headache before the trauma. Patients who experienced an increase of already-existing pre-traumatic headache used more analgesics than patients first suffering from headache after the trauma. Post-traumatic headache was reported by more women than men (p less than 0.02), the corresponding relative risk being 1.6. Both the use of analgesics and the frequency of headache showed a significant increase for patients with post-traumatic headache when compared with a "control group" of 41 patients with unchanged headache and when compared with all patients with headache before the trauma. There was no significant difference in the location of pain between the groups analysed.     

The nurse's role in mammography screening

Black women in Dade Country have a substantially higher proportion of advanced breast cancer at diagnosis than white women. To shift the stage at diagnosis from later to earlier, a Cancer Early Detection Program was initiated in the fall of 1987. This program involves screening with low-cost mammography, physical breast examination, and instruction in self-breast examination as well as general cancer education about prevention, early detection, and health promotion. The educational programs are presented in conjunction with the local unit of the American Cancer Society. A mobile mammography van travels to Primary Health Care Centers to provide mammograms to a population with limited access to preventive health care. This article describes the development and implementation of the program. It focuses on the responsibilities of an oncology nurse who coordinates and directs the program. Recommendations are made for ways oncology nurses can assume expanded roles in cancer screening/early detection.     

Anti-allodynic efficacy of the chi-conopeptide, Xen2174, in rats with neuropathic pain

Xen2174 is a structural analogue of Mr1A, a chi-conopeptide recently isolated from the venom of the marine cone snail, Conus marmoreus. Although both chi-conopeptides are highly selective inhibitors of the norepinephrine transporter (NET), Xen2174 has superior chemical stability relative to Mr1A. It is well-known that tricyclic antidepressants (TCAs) are also potent NET inhibitors, but their poor selectivity relative to other monoamine transporters and various G-protein-coupled receptors, results in dose-limiting side-effects in vivo. As TCAs and the alpha(2)-adrenoceptor agonist, clonidine, have established efficacy for the relief of neuropathic pain, this study examined whether intrathecal (i.t.) Xen2174 alleviated mechanical allodynia in rats with either a chronic constriction injury of the sciatic nerve (CCI-rats) or an L5/L6 spinal-nerve injury. The anti-allodynic responses of i.t. Mr1A and i.t. morphine were also investigated in CCI-rats. Paw withdrawal thresholds were assessed using calibrated von Frey filaments. Bolus doses of i.t. Xen2174 produced dose-dependent relief of mechanical allodynia in CCI-rats and in spinal nerve-ligated rats. Dose-dependent anti-allodynic effects were also produced by i.t. bolus doses of Mr1A and morphine in CCI-rats, but a pronounced 'ceiling' effect was observed for i.t. morphine. The side-effect profiles were mild for both chi-conopeptides with an absence of sedation. Confirming the noradrenergic mechanism of action, i.t. co-administration of yohimbine (100 nmol) with Xen2174 (10 nmol) abolished Xen2174s anti-allodynic actions. Xen2174 appears to be a promising candidate for development as a novel therapeutic for i.t. administration to patients with persistent neuropathic pain.