Gene frequencies of the HPA-1 and HPA-2 platelet antigen alleles among the Amerindians.

BACKGROUND AND OBJECTIVES: Platelet-specific alloantigens are important in neonatal alloimmune thrombocytopenia, posttransfusion purpura, refractoriness to platelet transfusions, and population genetics. Data are scarce on allele frequencies in ethnic groups other than whites and Asians. MATERIALS AND METHODS: Using allele-specific restriction enzyme analysis, we studied the distribution of HPA-1 and HPA-2 alleles in six Brazilian Amazon tribes of Amerindians, belonging to five different language stocks. We compared these with the values obtained for blacks and whites. RESULTS: Only the HPA-1a allele was found among 132 Amerindian chromosomes, compared with a gene frequency of HPA-1b of 0.115 and 0.113, respectively, among blacks and whites. The frequency of HPA-2b among the Amerindians (0.042) is lower than that obtained for blacks and whites (0.148 and 0.100, respectively), and the lowest thus far observed in a population of Asian origin. CONCLUSION: Differences in DNA polymorphisms in Amerindian populations have not only anthropological and genetic interest, but also practical applications when they involve coding regions that may change the functional or immunologic features of the protein.

Segregation analysis of microcephaly.

Microcephaly is a heterogeneous disorder with genetic and environmental causes. However, there is little information on what proportion of cases are caused by inherited susceptibility, or the mode of inheritance in familial cases. To address these questions, we have performed classical and complex segregation analyses for microcephaly on 2 sets of family data collected from genetic counseling clinics in Vancouver and Jerusalem. These samples consisted of 143 affected individuals in 127 families ascertained from Vancouver, and 101 affected individuals in 59 families ascertained from Jerusalem. The results of the segregation analyses for the Vancouver sample indicated that approximately half of all microcephaly cases were due to highly penetrant recessive mutant alleles, with the remainder being sporadic. Although a recessive model allowing for the occurrence of sporadic cases fit the data from Vancouver best, a dominant model could not be statistically rejected. The classical segregation analysis on the Jerusalem sample suggested that both a dominant model with 29% of the cases being sporadic and a purely recessive model provided adequate fit to the data. Although the complex segregation analysis of this sample indicated that a dominant model provided a more parsimonious explanation for the observed familial variation, a recessive model was only marginally rejected. It should be noted that in the Jerusalem sample, families tended to be ascertained in the genetic counseling clinic only after the birth of a second affected child. This could be a potential bias which could inflate the segregation ratio, thus giving the impression of dominant inheritance. Our analyses, while confirming the complex nature of the cause of microcephaly, indicate that it may be necessary to await the results of genetic linkage analysis before a definitive mode of inheritance can be determined.

Effects of ovarian hormone treatment on Ca(2+)-induced contractions and Ca(2+)-antagonism in the depolarized rat myometrium.

The effects of estrogen (E), progesterone (P) and estrogen plus progesterone (E+P) treatment on Ca-induced contraction in the KCL-depolarized uterine muscle, and the influences on the Ca2+ antagonism induced by reserpine and verapamil "in vitro" were studied. Uterine muscles from rats in estrus were taken as controls. Uteri from spayed untreated rats showed the same sensitivity to Ca2+ as those from estrus rats, but castration decreased maximal contractile tension to Ca2+ and Ca2+ threshold. P treatment failed to modified the effects of castration on the responses to Ca2+. E or E+P treatments decreased the sensitivity to Ca2+ but only E+P increased slope values and maximal contractile tension. E and E+P increased the potency of verapamil Ca2+ antagonism but none of the treatments modified reserpine direct inhibitory effects. The results obtained suggest that alterations on uterine contractility by hormone treatment are the result of complex interactions between both genomic effects on the contractile process as well as non-genomic direct actions of the hormones on Ca2+ membrane permeability.

Prenatal diagnosis of Charcot-Marie-Tooth disease type 1A (CMT1A) using molecular genetic techniques.

Charcot-Marie-Tooth disease type 1A (CMT1A) is a frequent hereditary motor and sensory neuropathy of the peripheral nerves. In most cases, the disease is associated with a 1.5 Mb tandem duplication at 17p11.2. A 42-year-old pregnant women requested prenatal diagnosis because of her age and since both her husband and two children were severely affected with CMT1. The CMT1A duplication was demonstrated in the father's, the two children's, and the fetus's DNA using different molecular genetic methods. Although cytogenetical analysis showed a normal female karyotype in the fetus, the parents decided to terminate the pregnancy because of the genetic risk associated with the CMT1A duplication.

Estimating the risk of a fetal autosomal trisomy at mid-trimester using maternal serum alpha-fetoprotein and age: a retrospective study of 142 pregnancies.

Risks appropriate for mid-trimester prenatal screening for autosomal trisomies have been estimated from a combination of maternal age and maternal serum (MS) alpha-fetoprotein (AFP) levels at 16-20 weeks gestation. Published data on the frequency of Down's syndrome births relative to maternal age were modified to include the additional age-related frequency of trisomy 18 and trisomy 13 cases to provide an overall risk for an autosomal trisomy at mid-trimester. MSAFP results from a retrospective study of 142 affected (114 trisomy 21, 19 trisomy 18, and 9 trisomy 13) and 113,000 unaffected pregnancies were converted to multiples of the appropriate gestational median (MOM). The AFP levels in the autosomal trisomy pregnancies were found to be significantly reduced at 0.72 MOM of the unaffected pregnancies. Risks (likelihood ratios) were derived from the overlapping log Gaussian distributions for affected and unaffected pregnancies and combined with maternal age risks to give the overall odds of an affected pregnancy. A mid-trimester cut-off risk of 1:280 gave an estimated 37 per cent detection rate for autosomal trisomies in the west of Scotland population for a follow-up (false-positive) rate of 6.6 per cent. These figures compare with a 30 per cent detection and 6.7 per cent false-positive rate if age 35 years and over is used as the sole criterion for selection of at-risk pregnancies.

Screening for Down's syndrome in older women based on maternal serum alpha-fetoprotein levels and age: preliminary results.

We report the results of screening for Down's syndrome (DS) in older women using published rate schedules based on maternal serum alpha-fetoprotein (MSAFP) and age. Five hundred and seventeen patients aged 35 years and older, who were referred for a mid-trimester genetic amniocentesis, were first tested for MSAFP and then underwent an amniocentesis. Individual risks for DS, combining MSAFP and age, were derived using three different published rate schedules. Theoretical selection for amniocentesis was made using the cut-off level of the average collective risk for a 35-year-old woman (1:380 at live birth or 1:270 at amniocentesis). Six affected pregnancies (five with DS and one with trisomy 18), which were diagnosed prenatally, were all found to be at a higher risk than the specified cut-off. These cases would have been diagnosed in any event, using any of the published rate schedules. According to these rate schedules, between 39 and 45 per cent of the patients would be in the lower risk group and therefore would have been counselled not to undergo amniocentesis. Further studies should be conducted in order to reach conclusive screening policies for DS in older women.

Reserpine non-selectively inhibits rat uterus contraction in vitro.

1. Reserpine produced a direct in vitro non-selective inhibitory effect on smooth muscle contraction of endometrium-free rat uterus. 2. Reserpine uptake into uterine muscle and its antagonistic effect on contraction had a similar time course. 3. Reserpine had a relaxing effect similar to that of trifluoperazine and different from that of verapamil or papaverine, and also failed to exert any inhibitory effect on 45Ca uptake rate. 4. Both reserpine and trifluoperazine but not verapamil inhibited the acetylcholine-induced contraction when present during the Ca-release from intracellular stores. 5. It is hypothesized that reserpine exerts its inhibitory action intracellularly on the activation of smooth muscle contraction by sarcoplasmic Ca2+.

Specific opiate effects on dextran-induced inflammation in rats.

The effects of opiates were investigated in two models of acute inflammation in rats. Morphine (0.1-10 mg/kg, i.p.) inhibited by 50% the paw edema induced by interdigital injection of 1% dextran solution. Low but not high doses of naltrexone produced a similar degree of inhibition. Naltrexone (10 mg/kg, i.p.) completely prevented morphine antiedema effect. Local anesthesia of the hindleg with lidocaine neither modified dextran-induced paw edema nor morphine inhibitory effects. Morphine (10 mg/kg, i.p.) enhanced by 50% skin vascular permeability induced by intradermically injected 1% dextran solution. Again, naltrexone prevented morphine effects. The obtained results suggest a specific modulatory role of opiates in the acute inflammatory responses of the rat.

Specific opiate effects on dextran-induced inflammation in rats.

The effects of opiates were investigated in two models of acute inflammation in rats. Morphine (0.1-10 mg/kg, i.p.) inhibited by 50

the paw edema induced by interdigital injection of 1

dextran solution. Low but not high doses of naltrexone produced a similar degree of inhibition. Naltrexone (10 mg/kg, i.p.) completely prevented morphine antiedema effect. Local anesthesia of the hindleg with lidocaine neither modified dextran-induced paw edema nor morphine inhibitory effects. Morphine (10 mg/kg, i.p.) enhanced by 50

skin vascular permeability induced by intradermically injected 1

dextran solution. Again, naltrexone prevented morphine effects. The obtained results suggest a specific modulatory role of opiates in the acute inflammatory responses of the rat.

Specific opiate effects on dextran-induced inflammation in rats.

The effects of opiates were investigated in two models of acute inflammation in rats. Morphine (0.1-10 mg/kg, i.p.) inhibited by 50

the paw edema induced by interdigital injection of 1

dextran solution. Low but not high doses of naltrexone produced a similar degree of inhibition. Naltrexone (10 mg/kg, i.p.) completely prevented morphine antiedema effect. Local anesthesia of the hindleg with lidocaine neither modified dextran-induced paw edema nor morphine inhibitory effects. Morphine (10 mg/kg, i.p.) enhanced by 50

skin vascular permeability induced by intradermically injected 1

dextran solution. Again, naltrexone prevented morphine effects. The obtained results suggest a specific modulatory role of opiates in the acute inflammatory responses of the rat.

Amniotic fluid findings in women with high levels of chlamydial antibody.

A study was undertaken to examine possible transplacental passage of Chlamydia trachomatis from pregnant women who were seropositive for chlamydia, but with no cervical C. trachomatis infection. Forty asymptomatic pregnant women, scheduled for diagnostic amniocentesis at 15-19 weeks of gestation, were tested for the presence of high serum IgA and IgG chlamydial specific antibodies and for cervical chlamydia infection. Five (12.5%) had both high serum IgA and IgG antibody levels and 10 (25%) had high serum IgG antibody levels. Overall, 15 (37.5%) had high serum chlamydia specific antibody levels (all were free of cervical chlamydial infection). The evaluation of the amniotic fluid specimens of these 15 seropositive pregnant women, who were free of cervical chlamydial infection, proved negative for direct C. trachomatis antigen detection and for chlamydial IgA and IgG specific antibodies. These negative results could be attributed to the lack of transplacental passage of C. trachomatis or to the antimicrobial activity of amniotic fluid against C. trachomatis, which has been previously described. The discrepancy between maternal infection and maternal serum antibody levels may suggest that the serologic test does not predict the presence of an antigen in the cervix.

Amniotic fluid alpha-fetoprotein, gamma-glutamyltranspeptidase, and autosomal trisomies.

Alpha-fetoprotein (AFP) concentration and gamma-glutamyltranspeptidase (GGT) activity have been analysed in amniotic fluid from a series of 65 pregnancies with autosomal trisomies. AFP values were reduced on average to 60 per cent of normal in cases of trisomy 21, but were not significantly different from normal in cases of trisomies 18 and 13. GGT activities were uniformly lower (44 per cent of normal) for all types of autosomal trisomy. A review of the literature indicates that over 85 per cent of Down's pregnancies but only 39 per cent of trisomy 18 and 13 pregnancies have amniotic fluid AFP levels below the normal median value, while the corresponding figures for GGT are 91 per cent for Down's syndrome and 96 per cent for trisomies 18 and 13.

Prenatal diagnosis of the pterygium syndrome.

We report two second trimester pregnancy terminations in the same woman following intrauterine ultrasonic findings of hydrops fetalis, polyhydramnios, lack of fetal movements, and short, fixed malformed limbs. One fetus also showed a cystic mass at the back of the head. Radiographic and anatomic studies of the fetuses demonstrated multiple pterygia, flexion contracture of multiple joints, abnormal facial appearance, cleft palate, pulmonary hypoplasia, and gracile bones. The cystic mass of the back of the head was found to be a cystic hygroma. These findings are consistent with the lethal variant of multiple pterygium syndrome. Early prenatal diagnosis of this condition is possible using ultrasonography.