HLA-DQB1 and HLA-DPB1 genotypes in severe preeclampsia.

OBJECTIVE: To clarify whether there are susceptible HLA-DQB1 or HLA-DPB1 alleles in women with preeclampsia. METHODS: The frequency of HLA-DQB1 and HLA-DPB1 alleles was analyzed in 47 women with previous severe preeclampsia and compared with that in 85 normal fertile women. The types of HLA-DQB1 and HLA-DPB1 alleles were assessed using a polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The frequency of HLA-DQB1*04 allele in previously preeclamptic women was 21.3% (20 of 94 loci) and in the controls was 11.2% (19 of 170 loci). Thus, the HLA-DQB1*04 allele frequency was significantly higher in preeclamptic women compared with controls (P <.05 by chi(2) test, OR 2.15, 95% confidence interval 1.08, 4.27). The frequency of other HLA-DQB1 alleles and all HLA-DPB1 alleles was not significantly different between groups. The incidence of homozygosity of HLA-DQB1 or HLA-DPB1 alleles in preeclamptic women was not significantly different compared with that of normal fertile women. CONCLUSION: These data suggest that women who have the HLA-DQB1*04 allele might be susceptible to preeclampsia.

Possible susceptibility of the HLA-DPB1*0402 and HLA-DPB1*04 alleles to unexplained recurrent abortion: analysis by means of polymerase chain reaction-restricted fragment length polymorphism method.

PROBLEM: To clarify whether HLA-DP antigens are associated with patient population of unexplained recurrent abortion. METHOD OF STUDY: The frequency of HLA-DPB1 alleles in patients with unexplained recurrent abortion, and the compatibility of HLA-DPB1 alleles between patient couples, were studied using a polymerase chain reaction (PCR)-restricted fragment length polymorphism (RFLP) method. Thirty patients who had a history of unexplained primary recurrent abortion, and their husbands, were typed for HLA-DPB1 genotype. Two hundred and ninety-nine base pair fragments from the second exon of HLA-DPB1 genes were selectively amplified using the PCR-primers. After amplification, the DNAs were digested with restriction endonucleases, and subjected to electrophoresis in a 12% polyacrilamide gel to determine HLA-DPB1 genotype. RESULTS: The frequency of HLA-DPB1*0402 and DPB1*04 alleles in the patient group (n = 30) was significantly increased, as compared to that in the normal fertile women (n = 30). The frequency of HLA-DPB1*04 allele in the patient group was significantly increased, as compared to that in the general population (n = 112). No significant compatibility of HLA-DPB1 alleles could be observed between patient couples and normal fertile couples. CONCLUSION: These findings suggest a possible new class II association with patient population of unexplained recurrent abortion.

Studies on the HLA-DRB1 genotypes in Japanese women with severe pre-eclampsia positive and negative for anticardiolipin antibody using a polymerase chain reaction-restriction fragment length polymorphism method.

The human leukocyte antigen (HLA)-DR genotype was determined in 54 Japanese women with severe pre-eclampsia in order to elucidate the relationship between HLA-DR antigen systems and pre-eclampsia. The patients were divided into two groups according to positivity for the anticardiolipin antibody (ACA), i.e. one patient group negative for ACA (n = 41) and the other patient group positive for ACA (n = 13). The frequency of each HLA-DRB1 allele in both groups was compared with that in 81 normally fertile Japanese women who had not experienced pre-eclampsia. The genotypes of HLA-DR antigens were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The frequency of DRB1*04 and DRB1*0403 in the patient group positive for the ACA was significantly higher compared with that in the group of normal fertile women (P< 0.05). The frequency of each HLA-DRB1 allele was not significantly different between patient group with pre-eclampsia negative for ACA and group of normal fertile women. These results suggest a difference in the immunogenetic background between the patient groups with severe pre-eclampsia positive and negative for the ACA.

Trizygotic pregnancy consisting of two fetuses and a complete hydatidiform mole with dispermic androgenesis.

A triplet pregnancy in a 23-year-old woman was terminated at 15 weeks of gestation because of her severe hypertension, lung edema, and secondary hyperthyroidism. The pregnancy consisted of a hydatidiform mole with a 46,XY karyotype and two fetuses each with 46,XX and a 46,XY karyotype. To determine the zygosity and genetic origin of the mole and fetuses, PCR- and computer-assisted genotyping were performed at 27 CA-repeat marker loci that were distributed evenly over the genome. As a result, genotypes of the three pregnancy products were distinct from each other, indicating that the triplets were trizygotic. The mole lacked any maternal alleles but inherited both of the paternal alleles and/or one paternal allele in duplicate. This, along with the XY sex chromosome constitution, indicated that the mole resulted from dispermic androgenesis. The mother developed a persistent trophoblastic tumor thereafter.

Human leukocyte antigen class II genotype in patients with recurrent fetal miscarriage who are positive for anticardiolipin antibody.

OBJECTIVE: To elucidate the relationship between human leukocyte antigen (HLA) class II genotypes and patients with recurrent fetal miscarriage who are positive for anticardiolipin antibody. DESIGN: Prospective clinical study. SETTING: Institutional practice at the outpatient clinic for infertility, Niigata University Medical Hospital. PATIENT(S): Patients with recurrent fetal miscarriage who were positive for anticardiolipin antibody and normal fertile women. INTERVENTION(S): Genomic DNA was extracted from peripheral mononuclear cells. MAIN OUTCOME MEASURE(S): Human leukocyte antigen class II genotype was determined using a polymerase chain reaction restriction fragment length polymorphism method. RESULT(S): The frequencies of DRB1*0403 and DRB1*0410 were significantly higher in the patient group than in the control group. The frequency of DRB1*04 also was significantly higher in the patient group. As for HLA-DQ genotype, the frequency of HLA-DQB1*0501 was significantly lower in the patient group. CONCLUSION: Human leukocyte antigen systems appear to be involved in the genesis of antiphospholipid syndrome.

HLA antigens in patients with severe preeclampsia.

The distribution of human leucocyte antigens (HLA) was analyzed in 35 patients with severe preeclampsia and compared with that in the general population in the Niigata district of Japan. The frequency of patients with HLA CW7 was significantly higher than that of the general population of this area (p < 0.05, Chi-square test). The frequency of those with HLA-DR6 (DR6, DR13 and DR14) was also significantly greater compared with the general population (P < 0.05, Chi-square test), while that of those with DR4 was significantly lower (P < 0.05, Chi-square test). The compatibility of HLA antigens in spouses was also analyzed in 20 patient couples and 26 normal fertile couples, and there was no significant difference. Thus it is suggested that HLA antigen systems might be involved in the genesis of preeclampsia.

A case of mosaic tetrasomy 12p (Pallister-Killian Syndrome) diagnosed prenatally: comparison of chromosome analyses of various cells obtained from the patient.

A pregnant woman was referred to our hospital at the 29th week of gestation with the symptom of polyhydramnios; diaphragmatic herniation of the fetus was suspected. Fetal chromosome anlaysis was performed using fibroblasts obtained by aminocentesis, and mosaicism of 46,XX and isochromosome of 12p were diagnosed. Out of 50 karyotyped cells, 19 (38.0%) showed the tetrasomy of the isochromosome of 12p. The mother vaginally delivered a baby girl who died just after delivery. The analysis of cord blood lymphocytes revealed only 0.5% incidence of tetrasomy of 12p. The incidence of tetrasomy was 8.0% for the placental chorionic villi, 48.0% for the fibroblasts obtained from the umbilical cord, and 70.0% for the skin fibroblasts. Thus, the diagnosis of Pallister-Killian Syndrome (PKS) is confirmed by mosaicism of i(12p), that is, the affected patients exhibit tissue-specific mosaicism, with the abnormal karyotype expression in limited lymphocytes, but marked in fibroblasts.

Treatment for patients with recurrent abortion with positive antiphospholipid antibodies using a traditional Chinese herbal medicine.

Twelve patients with recurrent abortion who had shown positive antiphospholipid antibodies were treated through the administration of a Japanese modified traditional Chinese herbal medicine Sairei-To (Chan ling-Tang) The patients had experienced a total of 27 spontaneous abortions in their previous pregnancies and had no other pregnancy history except for one patient. The patients were treated with 9.0 g of Sairei-To per day before their next pregnancy. The positive value of antiphospholipid antibodies returned to negative in 9 patients out of 12 patients through the treatment. Out of 12 patients, in 10 patients, their new pregnancy continued uneventfully and delivered an offspring (Success rate: 83.3%). Thus, the current treatment was considered to be an effective therapy for patients with recurrent abortion who were found to be positive for antiphospholipid antibodies.

[Clinical evaluation of granisetron injection against nausea and vomiting induced by anticancer drugs including cisplatin].

The antiemetic effect and safety of granisetron injection on nausea and vomiting induced by anticancer drugs were studied in the patients treated with anticancer drugs including 50 mg/m2 or more of cisplatin (CDDP). Granisetron is already on the market, and drip infusion of granisetron at 40 micrograms/kg has been used widely in clinical practice. In this clinical investigation, a simpler administration method of its slow (30 to 60 seconds) intravenous injection at 40 micrograms/kg just before CDDP administration was used. The clinical efficacy, safety and usefulness against nausea and vomiting were investigated in 22 patients, and the study medication was assessed as "remarkably effective" or "effective" in 16 patients (72.7%). Neither adverse experience nor abnormal laboratory test value was reported. In the usefulness rating, the study medication was assessed as "extremely useful" or "useful" in 16 out of 22 patients (72.7%). The above results have shown that the slow intravenous injection of granisetron has an excellent antiemetic effect on nausea and vomiting induced by anticancer drugs including CDDP and a high degree of safety.