Measurement of placental alkaline phosphatase in maternal plasma as an indicator of subsequent low birthweight outcome

Summary. Placental alkaline phosphatase (P-ALP) was measured by a specific monoclonal antibody-based immunoassay in plasma samples of 117 women who subsequently were delivered of an infant of birthweight less than 2·5 kg. P-ALP values > twice the normal median were found in 32% of maternal plasma samples from low birthweight cases in one scries and in 35% in another series, while in normal outcome controls the corresponding value was 8%. The differences were highly significant. The proportion of low birthweight cases with elevated maternal P-ALP values appears to be very similar between 15 and 34 weeks gestation. At 16–18 weeks gestation there is a significant positive correlation (r = 0·40) between P-ALP and maternal plasma alpha-fetoprotein (AFP) values in low birthweight cases. The use of P-ALP assay in combination with AFP assay appears to improve the detection of pregnancies with subsequent low birthweight outcome.     

Site-specific biotinylation

We have developed an expeditious method for the incorporation of the biotinylaminocaproyl moiety on the ε-amino group of a lysine residue within a peptide chain in a site-specific manner. Using t-Boc chemistry for the solid phase synthesis approach and a base labile, acid stable protecting group (Fmoc-) for the ε-amino group of the target lysine, we prepared fully protected resin bound peptides which are site-specifically biotinylated. Following HF cleavage, the uniquely biotinylated peptides were obtained in a high degree of purity. Using this approach, a number of biotinylaminocaproyllysyl derivatives of a monocyclic Endothelin-1 analog were prepared. Synthesis of selected bicyclic analogs of high affinity monocycles led to the preparation of the bicyclic [Nle⁷]ET-1 analog containing ε-biotinylaminocaproyllysine at position-9. This peptide, with K_d= 0.08 nM, has 1000-fold higher affinity for the ET_A receptor than the commercially available N_α-biotinylated Endothelin-1. The general utility of this biotinylation methodology was demonstrated by the synthesis of a site-specifically biotinylated PTH analog which contained several side chain functionalized amino acid residues in its sequence. The synthetic method reported here is convergent in that it allows the facile variation of the length of the spacer and also offers the potential to introduce in a site specific manner other groups such as affinity labels and fluorescent tags.     

Complete structure of eclosion hormone of Manduca sexta

The locations of the three disulfide bonds of eclosion hormone (EH) isolated from Manduca sexta were assigned by sequence analysis of thermolysin fragments and by comparison of a key heterodimeric fragment to regiospecifically synthesized parallel and antiparallel isomers. We elucidated the complete structure of Manduca EH as a 62-residue peptide which has three disulfide bonds between Cys¹⁴-Cys³⁸, Cys¹⁸-Cys³⁴, and Cys²¹-Cys⁴⁹.     

'Well-being': health promotion's red herring

‘Well-being’ is frequently said to be the ultimategoal of health promotion. However, health promotion author itiesdo no: offer a clear definition of ‘well-being’.Instead health promoters either assume a causal relationshipbetween their activities and the increase of ‘well-being’or claim privileged knowledge of ‘well-being’ andits means of production, or both. These health promotion strategiesare questioned, and it is suggested that the use of ‘well-being’in health promotion acts to obscure the analysis of health promotionphilosophy and practice. It is concluded that either the term‘well-being’ should be given clear and substantialcontent, or it should be discarded by health promoters. Thelatter option is favoured.     

Interferon Alfa-2b or Not 2b? Significant Differences Exist in the Decision-Making Process between Melanoma Patients Who Accept or Decline High-Dose Adjuvant Interferon Alfa-2b Treatment

BACKGROUND: Patients with thick (Breslow>4 mm) primary melanoma and/or regional nodal metastasis have a high risk of tumor recurrence. High-dose adjuvant interferon (IFN) alfa-2b offers/=50% risk of recurrence/disease-related mortality and offered IFN. Telephone surveys delineated reasons behind patients' decisions to accept IFN. RESULTS: Acceptors, 60 of 135 (45%), decided to take IFN alfa-2b whereas 75 of 135 (55%) declined. Being female (OR, 2.4; 95% CI, 1.17-5.03; p=.017) and positive SLN status (OR, 2.2; 95% CI, 1.01-4.97; p=.048) were strongly associated with patients who chose IFN. Acceptors of IFN were younger, more influenced by physicians, and less affected by depression and side effect profile (p<.05 for all). Decliners were more concerned by strained relationships with family and social life (p<.05). CONCLUSIONS: Gender and positive SLN were predictive of high-risk melanoma patients' acceptance of IFN treatment. Physician insight into melanoma patients' therapeutic decision-making process can guide patients through this difficult disease.     

Seminal Fluid and the Expression of MHC Class I Antigens in the Placenta of the Rat

PROBLEM : To determine whether seminal fluid influences the expression of MHC class I antigens on the surface of basal trophoblast cells in the placenta of the rat. METHODS : Transfer of DA × DA embryos into a WF (allogeneic) or DA (syngeneic) recipient made pseudopregnant by hormonal treatment followed by mating with a vasectomized male (seminal fluid) or by mechanical stimulation (no seminal fluid). Antigen expression was determined by electron microscopic immunocytochemistry using the appropriate gold-labeled monoclonal antibodies. RESULTS : Seminal fluid did not affect the expression of MHC class I antigens on the surface of the basal trophoblast in either allogeneic or syngeneic matings. CONCLUSIONS : The suppression of the expression of paternal class I antigens on the surface of the basal trophoblast cells in allogeneic pregnancies most likely occurs at the genome level shortly after fertilization.     

The Encapsulation of Squid Diisopropylphosphorofluoridate-Hydrolyzing Enzyme within Mouse Erythrocytes

This study describes the entrapment of squid-type diisopropylphosphorofluoridate-hydrolyzingenzyme (DFPase) within mouse red blood cells. These erythrocytesthereby gain the ability to rapidly hydrolyze alkylphosphatecholinesterase (ChE) inhibitors such as diisopropyl fluorophosphate(DFP). DFPase rapidly hydrolyzes DFP to diisopropyl phosphate.Resealed erythrocytes provide a stable carrier system that canpreserve the activity of encapsulated enzymes against otherwiserapid in vivo degradation; thus, ChE inhibitors can be degradedto relatively nontoxic metabolites by these erythrocyte carriers.Squid DFPase was purified from the hepatopancreas of Atlanticsquid and DFPase activity was determined by measuring changesin fluoride ion concentration using a fluoride ion selectiveelectrode. Mouse erythrocytes in suspension with excess squidDFPase were dialyzed against hypotonic buffer to allow the encapsulationof the enzyme to occur. Cells were then resealed by returningthe suspension to isosmotic with saline. Rate of DFP hydrolysisobserved with these cells was much greater than the rate ofnonenzymatic hydrolysis and was directly proportional to theamount of the erythrocyte suspension added to the assay solution.The rate of hydrolysis was first order in substrate. Erythrocytecontrols showed no endogenous DFPase activity. These resultssuggest that enzyme entrapment may be developed as a methodto prevent and antagonize organophosphate poisoning.     

Multicenter Evaluation of Fixed-Wire PTCA Catheters with Modified Distal Tips: Initial and 2-Month Follow-Up Results

Lesions in the distal portion of coronary arteries are technological challenges with currently available percutaneous transluminal coronary angioplasty (PTCA) equipment. A study was performed at multiple centers to determine if new "fixed-wire" devices with a modified distal tip (a 2-cm flexible tip and 1-cm standard tip) would be useful in these situations. Three hundred twenty-three patients were included in the study, 75% male, mean age 63 ± 11 years. Four hundred ninety-three lesions were attempted; the overall success rate was 85%. Forty-six (14.2%) clinical complications occurred including: 5 deaths (1.1%); 2 nonfatal myocardial infarctions (0.6%); and 6 emergency coronary artery bypass grafting procedures (2.6%). A device malfunction was noted in 32 patients (9.9%), and included: 8 balloon ruptures or perforations (2.0%); 6 bent or damaged tips (1.9%); and 4 shaft/manifold leaks (1.2%). Two-month follow-up assessment for restenosis was done in 352 of 371 (95%) patients and at that time 89% were asymptomatic, had a negative functional test, or patent PTCA site by angiography. The new fixed-wire PTCA catheters with 1- and 2-cm flexible tips hold promise for dilating lesions in distal locations with an acceptable rate of complications. Additional investigation is needed to determine their role in the treatment of coronary artery disease with PTCA.