Actual half-life of alpha-fetoprotein as a prognostic tool in pediatric malignant tumors

In a retrospective study, the prognostic value of monitoring the decay of alpha-fetoprotein (AFP) was assessed. Serum AFP was determined serially in 18 children with malignant germ-cell or hepatic tumors: 7 endodermal sinus tumor, 3 embryonal carcinoma, 5 malignant teratoma, 2 hepatoblastomas, and 1 hepatocellular carcinoma. The actual half-life (AHL) of AFP was computed after surgical resection of the tumor. In group 1, which had complete resection and no recurrence during follow-up (n = 13), the AHL of AFP was 4.0 +/- 0.9 days. In group 2, which had incomplete resection or recurrence during follow-up (n = 5), the AHL of AFP was 24.8 +/- 20 days, significantly longer than that of group 1 (P = 0.0026). The increased AHL of AFP indicated residual active tumor after surgical resection. The AHL of AFP may be more sensitive than serial monitoring of AFP in detecting preclinical recurrence after surgical resection of AFP-secreting tumors. Treatment strategies can be based on AFP clearance, and prospective clinical trials are warranted.     

Chronic residential crowding and children's well-being: an ecological perspective

Chronic residential crowding is associated with difficulties in behavioral adjustment at school, poor academic achievement, heightened vulnerability to the induction of learned helplessness, elevated blood pressure, and impaired parent-child interpersonal relationships among a sample of working-class, 10-to 12-year-old children living in urban India. The significant main effects of residential crowding on blood pressure and learned helplessness are moderated by gender. Residential crowding is positively associated with blood pressure only among boys and with helplessness only among girls. All analyses statistically control for household income. We then demonstrate that perceived parent-child conflict functions as an underlying, intervening process that largely accounts for several correlates of household crowding among children.     

A comparative study of death anxiety in hospice and emergency nurses

This paper describes a preliminary cross-sectional study which aimed to compare levels of death anxiety and coping responses in palliative care and accident and emergency (A & E) nurses. Forty-three nurses (23 from palliative care and 20 from A & E) were recruited from a district general hospital and nearby hospice. Both sites had the same mean annual death rate of 150 patients. Death anxiety was measured by the Death Attitude Profile-Revised Questionnaire and coping responses were elicited by a semi-structured interview. As hypothesized, hospice nurses had lower death anxiety and they were more likely to recall both good and difficult experiences related to patient care. Unlike the hospice nurses, a subgroup (20%) of A & E nurses reported that they were unable to discuss problems with colleagues. The study has implications for the development of institutional support for staff to enable nurses to provide good quality care for dying patients and bereaved people.     

Human testis-determining factor SRY binds to the major DNA adduct of cisplatin and a putative target sequence with comparable affinities

cis-Diamminedichloroplatinum(II) (cis-DDP or cisplatin) is a widely used anticancer drug that is most effective against tumors of the testis. Although cisplatin is believed to mediate its cytotoxicity through the formation of DNA adducts, the precise biochemical mechanisms underlying its antitumor activity and selectivity for testicular tumors remain elusive. Of significance are the high-mobility group (HMG) domain and other proteins that bind specifically to cisplatin-DNA adducts. The present study focuses on the testis-specific HMG domain protein human SRY (hSRY). The full-length hSRY protein and its HMG domain region alone were expressed in Escherichia coli and purified to homogeneity. The affinities and specificities of full-length hSRY and the hSRY-HMG domain for 20 bp DNAs containing a single cis-[Pt(NH3)2{d(GpG)-N7(1), -N7(2)}] intrastrand cross-link or a putative hSRY target site in the CD3epsilon gene enhancer (AACAAAG) were determined in electrophoretic mobility shift assays. Full-length hSRY bound to the major 1,2-d(GpG) cisplatin adduct with a Kd(app) of 120 +/- 10 nM and exhibited a 20-fold specificity over unmodified DNA. The HMG domain of hSRY was sufficient for this interaction. The hSRY-HMG domain recognized the 1,2-d(GpG) intrastrand cross-link with higher affinity [Kd(app) = 4 +/- 0.7 nM] but with lower specificity (5-fold) than the full-length protein. The affinities of full-length hSRY and the hSRY-HMG domain for a single cisplatin-DNA adduct were comparable to those for the putative target sequence AACAAAG. These data suggest that cisplatin-DNA adducts may compete with specific DNA sequences in vivo for the binding of human SRY. A possible role for this testis-specific protein in the cytotoxicity and organotropic specificity of cisplatin for testicular tumors is proposed.     

Development of heart inter-beat interval variability in preweanling rats: effects of exposure to alcohol and hypoxia

In the previous work (M. Yu. Shchelkanov, A. N. Yudin, A. V. Antonov, N. S. Starikov, A. A. Vedenov, E. V. Karamov, J. Biomol. Struct. Dyn. 15, 217-229 (1997)) we have introduced the amino acid distribution function within HIV-1 taxons and Hamming-transformed Euclidean measures between their characteristics: consensus, subconsensus and sample mean. In this work the referred characteristics are used for hierarchical classification of amino acid sequences of gp120 V3 region belonging to different HIV-1 taxons. A comparative analysis of the results produced by various classification methods is carried out. Multidimensional scaling of distance matrix for the specified characteristics is used to visualize the pattern of HIV-1 variability.     

Buttockectomy as a limbsaving procedure for locally advanced soft tissue sarcoma of the buttock region

Cord blood was obtained from 164 neonates at birth and investigated for the presence of aflatoxins. 14 of the samples were neonates without jaundice and 150 from neonates with jaundice. There was significant reduction (P > 0.05) in birth weight of jaundiced neonates with aflatoxin. Neonates with jaundice have high mean concentration of aflatoxin B1 (32.3 ng/ml and 35.6 ng/ml). Aflatoxin G1 was not detected in any of the groups. The rate of detection was higher in wet (81.8%) than dry season (50.0%). These findings show that neonates are exposed to aflatoxin prenatally and that high incidence of jaundice occurred in the wet warm months.     

Arthroscopic anterior cruciate ligament reconstruction using autogenous hamstring tendon graft without detachment of the tibial insertion

This article describes a modified arthroscopic technique of anterior cruciate ligament reconstruction using quadrupled hamstring tendon graft. The autogenous semitendinosus and gracilis grafts are harvested without detachment of the tibial insertion. To obtain longer grafts, the accessory tibial insertions of the hamstring tendons are dissected. The EndoButton (Acufex Microsurgical, Andover, MA) is used for femoral fixation and two spiked staples are used for tibial fixation in a belt buckle fashion. Then the residual anterior laxity is restored by additional absorbable interference screw fixations. In this technique, more viable graft is obtained and more firm distal fixation is achieved by preservation of the tibial insertion of hamstring tendons.     

CSF testosterone and 5-HIAA correlate with different types of aggressive behaviors

We studied the potential roles of testosterone and serotonin in various forms of aggressive and violent behaviors by measuring each biochemical and behaviour in free-ranging adolescent male nonhuman primates. Our results showed that (1) CSF free testosterone concentrations were positively correlated with overall aggressiveness, but not with measures of impulsivity. (2) CSF 5-HIAA concentrations were negatively correlated with impulsive behavior, and severe, unrestrained aggression, but not with overall rates of aggression. High rates of impulsive behavior were positively correlated with severe, unrestrained aggression, but not overall rates of aggression. (3) Dimensional analyses showed that while subjects with low CSF 5-HIAA exhibited high rates of aggression, high CSF testosterone further augmented rates and intensity of aggression in subjects with low CSF 5-HIAA. We conclude that high CSF free testosterone concentrations are associated with competitive aggression, while low CSF 5-HIAA concentrations are associated with severe aggression which results from impaired impulse control, and perseverance.     

5,5-trans lactone-containing inhibitors of serine proteases: identification of a novel, acylating thrombin inhibitor

Synthesis of a variety of 5,5-trans fused lactones, related to compounds found in extracts of Lantana camara, has provided a series of novel acylating inhibitors of human thrombin, trypsin, chymotrypsin and human leucocyte elastase. The most effective thrombin inhibitor is 7 with an IC50 of 130 nM and a Kobs/[1] of 4,000 M-1 s-1.     

Presence and consequence of uracil in preneoplastic DNA from folate/methyl-deficient rats

Uracil can arise in DNA by misincorporation of dUTP into nascent DNA and/or by cytosine deamination in established DNA. Based on recent findings, both pathways appear to be promoted in the methyl-deficient model of hepatocarcinogenesis. A chronic increase in the ratio dUTP:dTTP with folate/methyl deficiency can result in a futile cycle of excision and reiterative uracil misincorporation leading to premutagenic apyrimidinic (AP) sites, DNA strand breaks, DNA fragmentation and apoptotic cell death. The progressive accumulation of unmethylated cytosines with chronic methyl deficiency will increase the potential for cytosine deamination to uracil and further stress uracil mismatch repair mechanisms. Uracil is removed by a highly specific uracil-DNA glycosylase (UDG) leaving an AP site that is subsequently repaired by sequential action of AP endonuclease, 5'-phosphodiesterase, a DNA polymerase and DNA ligase. Since the DNA polymerases cannot distinguish between dUTP and dTTP, an increase in dUTP:dTTP ratio will promote uracil misincorporation during both DNA replication and repair synthesis. The misincorporation of uracil for thymine (5-methyluracil) may constitute a genetically significant form of DNA hypomethylation distinct from cytosine hypomethylation. In the present study a significant increase in the level of uracil in liver DNA as early as 3 weeks after initiation of folate/methyl deficiency was accompanied by parallel increases in DNA strand breaks, AP sites and increased levels of AP endonuclease mRNA. In addition, uracil was also detected within the p53 gene sequence using UDG PCR techniques. Increased levels of uracil in DNA implies that the capacity for uracil base excision repair is exceeded with chronic folate/methyl deficiency. It is possible that enzyme-induced extrahelical bases, AP sites and DNA strand breaks interact to negatively affect the stability of the DNA helix and stress the structural limits of permissible uracil base excision repair activity. Thus substitution of uracil for thymine induces repair-related premutagenic lesions and a novel form of DNA hypomethylation that may relate to tumor promotion in the methyl-deficient model of hepatocarcinogenesis.