Use of the chemical cleavage of mismatch method for prenatal deficiency diagnosis of alpha-1-antitrypsin

The most common mutation in alpha-1-antitrypsin deficiency, conversion of a G to an A at base 9989 (PI-Z), was detected with the chemical cleavage of mismatch method, demonstrating the power of the method for prenatal diagnosis. Exon V of the gene was amplified using the polymerase chain reaction and heteroduplexes were formed to test for the presence of the mutation. The predicted C mismatch was readily detectable with hydroxylamine, and by making the probe from the chorionic villus sample it was possible to determine that the fetus was heterozygous, not homozygous, for the mutation.     

Rare non-mosaic trisomies in chorionic villus tissue not confirmed at amniocentesis

This paper reports eight cases of non-mosaic, rare, and typically lethal trisomies diagnosed in chorionic villi and not confirmed by amniocentesis. Four cases were 47,XX, + 16; two cases were 47,XX, +2; one was 47,XX, + 12; and one was 47,XY, +7. There have been no known complications in any of these gestations. These eight cases were found in a series of approximately 12 000 samples processed in our laboratory (0.07 per cent). We conclude that (1) rare non-mosaic trisomy not reflecting the fetal condition is an occasional source of diagnostic ambiguity in chorionic villus sampling; and (2) when encountered, a follow-up amniocentesis should be recommended to the patient to confirm or rule out the abnormality. We propose the term ‘confined placental abnormality’ to describe non-mosaic trisomies and other related abnormalities found only in chorionic tissue.     

Climate change and temperature-dependent biogeography: oxygen limitation of thermal tolerance in animals

Recent years have shown a rise in mean global temperatures and a shift in the geographical distribution of ectothermic animals. For a cause and effect analysis the present paper discusses those physiological processes limiting thermal tolerance. The lower heat tolerance in metazoa compared with unicellular eukaryotes and bacteria suggests that a complex systemic rather than molecular process is limiting in metazoa. Whole-animal aerobic scope appears as the first process limited at low and high temperatures, linked to the progressively insufficient capacity of circulation and ventilation. Oxygen levels in body fluids may decrease, reflecting excessive oxygen demand at high temperatures or insufficient aerobic capacity of mitochondria at low temperatures. Aerobic scope falls at temperatures beyond the thermal optimum and vanishes at low or high critical temperatures when transition to an anaerobic mitochondrial metabolism occurs. The adjustment of mitochondrial densities on top of parallel molecular or membrane adjustments appears crucial for maintaining aerobic scope and for shifting thermal tolerance. In conclusion, the capacity of oxygen delivery matches full aerobic scope only within the thermal optimum. At temperatures outside this range, only time-limited survival is supported by residual aerobic scope, then anaerobic metabolism and finally molecular protection by heat shock proteins and antioxidative defence. In a cause and effect hierarchy, the progressive increase in oxygen limitation at extreme temperatures may even enhance oxidative and denaturation stress. As a corollary, capacity limitations at a complex level of organisation, the oxygen delivery system, define thermal tolerance limits before molecular functions become disturbed.     

Carbon mitigation potential and costs of forestry options in Brazil,China, India,Indonesia, Mexico,the Philippines and Tanzania

This paper summarizes studies of carbon (C) mitigation potential and costs of about 40 forestry options in seven developing countries. Each study uses the same methodological approach – Comprehensive Mitigation Assessment Process (COMAP) – to estimate the above parameters between 2000 and 2030. The approach requires the projection of baseline and mitigation land-use scenarios. Coupled with data on a per ha basis on C sequestration or avoidance, and costs and benefits, it allows the estimation of monetary benefit per Mg C, and the total costs and carbon potential. The results show that about half (3.0 Pg C) the cumulative mitigation potential of 6.2 Petagram (Pg) C between 2000 and 2030 in the seven countries (about 200× 10⁶ Mg C yr^-1) could be achieved at a negative cost and the remainder at costs ranging up to $100 Mg C^-1. About 5 Pg C could be achieved, at a cost less than $20 per Mg C. Negative cost potential indicates that non-carbon revenue is sufficient to offset direct costs of these options. The achievable potential is likely to be smaller, however, due to market, institutional, and sociocultural barriers that can delay or prevent the implementation of the analyzed options.     

Preimplantation genetic diagnosis of the fragile X syndrome by use of linked polymorphic markers

Fragile X syndrome is the most common cause of familial mental retardation. The most common mutation is expansion of a triplet (CGG)_n repeat in the 5′ untranslated region of the FMR1 gene on Xq27.3. The expansion is refractory to PCR due to preferential amplification of the smaller allele in heterozygous cells and the high GC content of the repeat and surrounding sequences. Direct detection of the normal parental alleles in preimplantation embryos has been used for preimplantation genetic diagnosis (PGD) of this disorder. However, this approach is only suitable for approximately 63% of couples due to the heterozygosity of the repeat in the normal population. As an alternative we investigated the use of polymorphic markers flanking the mutation to track the normal and premutation carrying maternal chromosomes in preimplantation embryos. Using a panel of 11 polymorphisms, six (CA)_n repeats and five single nucleotide polymorphisms, diagnosis was developed for 90% of referred couples. Multiplex amplification of informative markers was tested in 300 single buccal cells from interested couples with efficiency and allele drop out (ADO) rates ranging from 69% to 96% and 6% to 18%, respectively. Use of this approach is accurate and applicable to a larger number of patients at risk of transmitting fragile X to their offspring. Copyright © 2001 John Wiley & Sons, Ltd.     

Second-trimester maternal serum alpha-fetoprotein (MSAFP) iselevated in women with adverse pregnancy outcome associated with inherited thrombophilias

Obstetric complications, such as severe pre-eclampsia, fetal growth restriction, abruptio placentae, or stillbirth are associated with abnormally elevated second-trimester maternal serum alpha-fetoprotein (MSAFP) and β subunit of human chorionic gonadotrophin (βhCG). This has been attributed to placental abnormalities. Women with thrombophilias have been shown to have abnormalities of the placenta resulting in adverse pregnancy outcome in these patients. The purpose of the present study was to evaluate whether women with pregnancy complications and inherited thrombophilias have abnormally elevated second-trimester MSAFP or βhCG. Sixty-two women with pregnancy complications were tested for inherited thrombophilias several months after delivery. The thrombophilia group included 29 women with pregnancy complications and an inherited thrombophilia and the control group included 33 other patients without thrombophilia. Patients in the thrombophilia group had a higher median MoM MSAFP compared to the controls (1.337 vs 1.086, p=0.0516). The incidence of abnormally elevated MSAFP (>2.5 MoM) was also significantly higher in the thrombophilia group compared to controls (21% vs 3%, p=0.04). Neither the median MoM βhCG nor the incidence of abnormally elevated βhCG were significantly different between the groups. We conclude that second trimester MSAFP, but not βhCG, is abnormally elevated in patients with thrombophilia and obstetric complications. Copyright © 2001 John Wiley & Sons, Ltd.     

Confined placental mosaicism for trisomy 14 and maternal uniparental disomy in association with elevated second trimester maternal serum human chorionic gonadotrophin and third trimester fetal growth restriction

A case of confined placental mosaicism (CPM) and maternal uniparental isodisomy 14 identified after placental karyotype revealed trisomy 14 in a newborn with intrauterine growth restriction (IUGR) and minor dysmorphic features is reported. During the second trimester of the pregnancy, multiple marker screening revealed an increased risk for Down syndrome of >1 in 10. The maternal serum human chorionic gonadotrophin (MShCG) was markedly elevated at 4.19 MoM. Amniocentesis revealed a normal 46,XX karyotype. Fetal growth restriction has been associated with elevated MShCG and placental aneuploidy with CPM for chromosomes 2, 7, 9 and 16. The present case of CPM for chromosome 14 was also associated with fetal growth restriction and elevated second trimester MShCG, suggesting a common link. Further studies need to be done to determine if indeed elevation of second trimester MShCG is associated with increased risk of CPM. The present case again demonstrates the need to perform placental karyotype in unexplained fetal growth restriction. Copyright © 2001 John Wiley & Sons, Ltd.     

Pulmonary stenosis and reactive right ventricular hypertrophy in the recipient fetus as a consequence of twin-to-twin transfusion

The present study describes an association between adverse outcome in the twin-to-twin transfusion syndrome (TTTS) and pulmonary stenosis or reactive right ventricular hypertrophy. Six discordant monozygotic twin pregnancies with TTTS are described. Ventricular hypertrophy and atrioventricular valvular regurgitation occurred in all the recipient twins with pulmonary valvular stenosis in three cases and infundibular stenosis in one case. The recipient twin in one pair and both twins in another pregnancy died as a consequence of immaturity but the remaining twins all survived. Surgical intervention was required in one baby for valvular pulmonary stenosis. Our observations suggest that elevated blood pressure in the transfusion recipient may play an important role in pathogenesis. We hypothesise that both pulmonary stenosis and right chamber hypertrophy are secondary to hemodynamic changes. Although we have found valvular pulmonary stenosis in three recipients and infundibular stenosis in only one, this (obstruction to outflow) could be due to right chamber hypertrophy. Copyright © 2001 John Wiley & Sons, Ltd.     

Resourcefulization approaches to pollution control of chromate residues in China

Over 2 million tons of chromate residues as hazardous wastes have been accumulated from chromate production processes during the past more than 30 years in China. Some serious pollution problems have been caused due to no appropriate technology and management. Approaches are reviewed to pollution control of chromate residues by utilizing them as secondary resources in this paper. In addition to legislation for pollution control, chromate residues can be used as raw materials to produce a great diversity of useful industrial products. Strategies are also recommanded for the resourcefulization of chromate residues.