EFFECT OF RBD MUTATIONS IN SPIKE GLYCOPROTEIN OF SARS-COV-2 ON NEUTRALIZING IGG AFFINITY.

Certain mutant strains of SARS-CoV-2 are known to spread widely among humans, including the receptor binding domain (RBD) mutant, Y453F, from farmed minks, and the RBD mutant, N501Y, a mutation common to three major SARS-CoV-2 subvariants (B.1.1.7, B.1.351, and B.1.1.248) and omicron type SARS-CoV-2 BQ.1.1 and XBB.1.16 subvariants. We investigated the characteristics of the RBD mutants, Y453F and N501Y, using three-dimensional structural analysis. We also investigated the effect of Y453F, N501Y or the mutants of RBD of omicron type SARS-CoV-2 BQ.1.1 and XBB.1.16 subvariants on neutralizing antibodies in serum derived from individuals including children (aged 5-11 years) inoculated with mRNA based COVID-19 vaccine (BNT162b2: Pfizer/BioNTech) or COVID-19-positive patients or children (aged 5-11 years) after vaccination with BNT162b2. Our results suggest that SARS-CoV-2 subspecies with the RBD mutations Y453F or N501Y partially escaped detection by 4 neutralizing monoclonal antibodies and 21 neutralizing antibodies in serums derived from COVID-19-positive patients. The significantly low antibody titer of children against Omicron type SARS-CoV-2 BQ.1.1 subvariant and XBB.1.16 subvariant in Japan. Infection with SARS-CoV-2 subspecies that causes serious symptoms in humans may spread globally. In particular, since the antibody titer against the omicron type is low in children (aged 5-11 years) who have been vaccinated with conventional vaccines, therefore it is important for children to receive vaccines specific for the omicron type.

POTENTIAL LIFE PROGNOSTIC MARKER FOR MESENCHYMAL TUMOR RESEMBLING UTERINE LEIOMYOSARCOMA.

Benign uterine leiomyoma (U.LMA) and malignant uterine leiomyosarcoma (U.LMS), both uterine mesenchymal tumors, are distinguished by the number of cells exhibiting mitotic activity. However, uterine mesenchymal tumors contain tumor cells with various cell morphologies; therefore, making a diagnosis, including differentiating between benign and malignant tumors, is difficult. For example, cotyledonoid dissecting leiomyoma (CDL) or uterine smooth muscle tumors of uncertain malignant potential (STUMPs) are a group of uterine mesenchymal tumors for which a differential diagnosis is challenging. To date, a standardized classification system for uterine mesenchymal tumors has not yet been established. Furthermore, definitive preoperative imaging techniques or hematological examinations for the potential inclusion of CDL or STUMP in the differential diagnosis have not been defined. Several clinical studies have reported that there is no correlation between biomarker expression and mitotic rate or tumor recurrence. The immunohistochemical biomarkers reported so far cannot effectively help determine the malignant potential of CDL or STUMPs in patients who wish to become pregnant in the future. The establishment of gene expression profiles or detection of pathogenic variants by using next-generation molecular techniques can facilitate disease prediction, diagnosis, treatment, and prognosis. We examined the oncological properties of STUMP in adults using molecular pathological techniques on tissue excised from patients with uterine mesenchymal tumor. In a clinical study conducted by our medical team, the results of gene expression profiling indicated factors that may be associated with malignancy of uterine mesenchymal tumors. We herein describe the problems in diagnosing uterine mesenchymal tumors along with the results of the latest clinical studies. It is expected that the establishment of a diagnostic method targeting the characteristics of mesenchymal tumor cells will lead to the treatment of malignant tumors with a low risk of recurrence and metastasis.

Phase III randomised controlled trial of neoadjuvant chemotherapy plus radical surgery vs radical surgery alone for stages IB2, IIA2, and IIB cervical cancer: a Japan Clinical Oncology Group trial (JCOG 0102).

BACKGROUND: A phase III trial was conducted to determine whether neoadjuvant chemotherapy (NACT) before radical surgery (RS) improves overall survival. METHODS: Patients with stage IB2, IIA2, or IIB squamous cell carcinoma of the uterine cervix were randomly assigned to receive either BOMP (bleomycin 7 mg days 1-5, vincristine 0.7 mg m(-2) day 5, mitomycin 7 mg m(-2) day 5, cisplatin 14 mg m(-2) days 1-5, every 3 weeks for 2 to 4 cycles) plus RS (NACT group) or RS alone (RS group). Patients with pathological high-risk factors received postoperative radiotherapy (RT). The primary end point was overall survival. RESULTS: A total of 134 patients were randomly assigned to treatment. This study was prematurely terminated at the first planned interim analysis because overall survival in the NACT group was inferior to that in the RS group. Patients who received postoperative RT were significantly lower in the NACT group (58%) than in the RS group (80%; P=0.015). The 5-year overall survival was 70.0% in the NACT group and 74.4% in the RS group (P=0.85). CONCLUSION: Neoadjuvant chemotherapy with BOMP regimen before RS did not improve overall survival, but reduced the number of patients who received postoperative RT.

The course of pregnancy and childbirth in three mothers with recessive dystrophic epidermolysis bullosa.

BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is an autosomal recessive skin disease caused by mutations in the type VII collagen gene (COL7A1), resulting in detachment of the entire epidermis due to loss or hypoplasticity of the anchoring fibrils that normally secure the basement membrane to the underlying dermis. Trauma-induced blistering is often complicated by chronic erosions and scarring. From that perspective, pregnancy in RDEB might be considered an indication for elective caesarean section in a bid to minimize perineal blistering. To date, only four cases of pregnancy and delivery in patients with RDEB have been reported. CASES: We report three more women, each with RDEB-generalized other (RDEB-GO), all of whom had successful vaginal deliveries without major cutaneous or mucosal complications. One woman also had a second child, by vaginal delivery, indicating a lack of vaginal stenosis after the first birth. CONCLUSIONS: These cases show that RDEB-GO is not an absolute primary indication for elective caesarean section and that, perhaps surprisingly, genital/perineal blistering and scarring are not inevitable consequences of childbirth. Moreover, breastfeeding is also feasible in women with RDEB-GO.

Efficacy of neoadjuvant chemotherapy followed by radical hysterectomy in locally advanced non-squamous carcinoma of the uterine cervix: a retrospective multicenter study of Tohoku Gynecologic Cancer Unit.

OBJECTIVE: Radical hysterectomy (RH) is a standard treatment for locally advanced non-squamous cell carcinoma (N-SCC) of the uterine cervix, but there have been no reports on whether neoadjuvant chemotherapy (NAC) followed by radical hysterectomy could improve the outcome of patients with this disease. MATERIALS AND METHODS: This multicenter retrospective study enrolled 77 patients with Stage IB2 to IIB N-SCC of the uterine cervix. Of these, 27 patients were treated with NAC prior to radical hysterectomy (NAC group) and 50 with RH alone (RH group). The two-year recurrence-free survival (RFS) rate, progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Clinical parameters such as clinical stage, histological type, and postoperative treatment were also examined between the groups. RESULTS: While the two-year RFS rates were 81.5% and 70.0% in NAC and RH groups, respectively (p = 0.27) and the median PFS was 51 months and 35 months in NAC and RH groups, respectively (p = 0.35), the median OS was 58 months and 48 months in NAC and RH groups, respectively, which was significant (p = 0.0014). The median OS of patients with mucinous adenocarcinoma in NAC group was significantly higher than that in RH group: 58 months versus 37 months (p = 0.03). CONCLUSION: NAC prior to RH may offer the prognostic advantage of patients with locally advanced N-SCC of the uterine cervix, especially mucinous adenocarcinoma.

Randomized phase II study comparing docetaxel plus cisplatin, docetaxel plus carboplatin, and paclitaxel plus carboplatin in patients with advanced or recurrent endometrial carcinoma: a Japanese Gynecologic Oncology Group study (JGOG2041).

BACKGROUND: The purpose of this study is to assess the efficacy and safety of treatment with taxane plus platinum in combination therapies for advanced or recurrent endometrial carcinoma. PATIENTS AND METHODS: Patients with measurable disease derived from histologically confirmed stage III/IV or recurrent endometrial carcinoma were randomly assigned to receive docetaxel plus cisplatin (DP), docetaxel plus carboplatin (DC), or paclitaxel plus carboplatin (TC) every 3 weeks until disease progression or adverse events prohibited further therapy. Among these regimens, the study evaluated the tumor response rate as the primary end point as well as toxicity. RESULTS: Ninety patients were enrolled. Of them, 88 were eligible and consequently 29, 29, and 30 patients were randomly assigned to DP, DC, and TC, respectively. Tumor response rates were 51.7%, 48.3%, and 60.0% in DP, DC, and TC, respectively (P = 0.65). The following toxic effects were observed: grade 3/4 neutropenia in 83.3%, 90.0%, and 76.6%; febrile neutropenia in 10.0%, 6.7%, and 3.3%; grade 3/4 thrombocytopenia in 6.7%, 10.0%, and 10.0%; grade 3/4 diarrhea in 13.3%, 3.3%, and 0%, respectively; and grade 3 neurotoxicity in 10.0% of TC. These toxicity profiles were not significantly different. CONCLUSION: The taxane plus platinum combination therapies could be candidates in further phase III trials for endometrial carcinoma.

Paternal height has an impact on birth weight of their offspring in a Japanese population: the Japan Environment and Children's Study.

This study examines the relationship between paternal height or body mass index (BMI) and birth weight of their offspring in a Japanese general population. The sample included 33,448 pregnant Japanese women and used fixed data, including maternal, paternal and infant characteristics, from the Japan Environment and Children's Study (JECS), an ongoing nationwide birth cohort study. Relationships between paternal height or BMI and infant birth weight [i.e., small for gestational age (SGA) and large for gestational age (LGA)] were examined using a multinomial logistic regression model. Since fetal programming may be a sex-specific process, male and female infants were analyzed separately. Multivariate analysis showed that the higher the paternal height, the higher the odds of LGA and the lower the odds of SGA in both male and female infants. The effects of paternal BMI on the odds of both SGA and LGA in male infants were similar to those of paternal height; however, paternal height had a stronger impact than BMI on the odds of male LGA. In addition, paternal BMI showed no association with the odds of SGA and only a weak association with the odds of LGA in female infants. This cohort study showed that paternal height was associated with birth weight of their offspring and had stronger effects than paternal BMI, suggesting that the impact of paternal height on infant birth weight could be explained by genetic factors. The sex-dependent effect of paternal BMI on infant birth weight may be due to epigenetic effects.

Vesicouterine ligament contains abundant autonomic nerve ganglion cells: the distribution in histology concerning nerve-sparing radical hysterectomy.

The aim of this study is to describe the histologic architecture of the tissues corresponding to the surgically developed connective tissue bundle commonly referred to as the posterior leaf of the vesico-uterine ligament (VUL), and to examine distribution of ganglion cells. Serial macroscopic slices, each 15-20 mm in thickness, were made from eight specimens (obtained from six female elderly cadavers). In these macroslices, the location of the deep uterine vein was used to identify the deep leaf of the VUL. The specimens were trimmed and semi-serial histologic sections in thickness were prepared at 1 mm intervals. Vesical veins and the associated nerve elements were enclosed by fascia and formed a common pedicle. The base of the pedicle contained the deep uterine vein trunk. The fascia encircling the pedicle varied in thickness and connective intensity between specimens. This vesical neurovascular bundle contained abundant ganglion cells. On average, 48.0% of the ganglion cells along the vesical tributaries of the deep uterine vein were located on the medial or vaginal side of the veins, 19.2% were located between veins, 13.0% on the lateral side of the veins, and 19.8% on the dorsal side. The interindividual variability was greatest on the dorsal side of vesical veins and ranged 11-202 cells. We conclude that in order to achieve maximal preservation of the ganglion cells during the surgical dissection of the posterior leaf of the VUL, care must be taken when the medial or vesical aspect of the ligament is separated. The standard nerve-sparing radical hysterectomy should be modified to reflect differences in the distribution of ganglion cells and in connective intensity between ganglions and veins.

Low response rate of second-line chemotherapy for recurrent or refractory clear cell carcinoma of the ovary: a retrospective Japan Clear Cell Carcinoma Study.

Clear cell carcinoma (CCC) of the ovary has been recognized to show resistance to anticancer agents in the first-line chemotherapy. Our aim was to evaluate the effect of second-line chemotherapy in a retrospective study. A total of 75 patients diagnosed with CCC and treated between 1992 and 2002 in collaborating hospitals were reviewed. Criteria for the patients' enrollment were 1) diagnosis of pure-type CCC at the initial operation, 2) treatment after one systemic postoperative chemotherapy, 3) measurable recurrent or refractory tumor, 4) at least two cycles of second-line chemotherapy and assessable for the response, and 5) adequate clinical information. Regimens of first-line chemotherapy were conventional platinum-based therapy in 33 cases, paclitaxel plus platinum in 24 cases, irinotecan plus platinum in 9 cases, and irinotecan plus mitomycin C in 7 cases. Treatment-free periods were more than 6 months in 24 cases (group A) and less than 6 months in 51 cases (group B). In group A, response was observed in two cases (8%): one with conventional platinum therapy and another with irinotecan plus platinum. In group B, three cases (6%) responded: two with platinum plus etoposide and one case with irinotecan plus platinum. Median overall survival was 16 months in group A and 7 months in group B (P = 0.04). These findings suggest recurrent or resistant CCC is extremely chemoresistant, and there is only small benefit of long treatment-free period in CCC patients. Another strategy including molecular-targeting therapy is warranted for the treatment of recurrent or refractory CCC.

Expression of CD44 in normal human versus tumor endometrial tissues: possible implication of reduced expression of CD44 in lymph-vascular space involvement of cancer cells.

Alternatively spliced variants of the CD44 molecule have been found to be associated with invasive and metastatic potential of cancer cells and poor prognosis in several types of carcinoma. We have examined expression of CD44 in normal and cancerous tissues of the endometrium as well as in cell lines established from patients with endometrial cancers by the combination of reverse transcription-polymerase chain reaction and Southern blot hybridization and by cell surface staining with antibodies to CD44. Of eight cancer cell lines tested, two lines, HOOUA and HEC50B, both of which are possibly potential candidates for metastasis, expressed a very small amount of mRNA for CD44. Variant forms of CD44 were expressed in 9 of 11 (81.8%) normal endometria, whereas 8 of 47 (17.0%) endometrial carcinomas showed expression of the variants. Hyperplasia samples displayed the variant expression in 42.9% of specimens (the value was between those of the normal and cancerous cells) and none of 3 in Müllerian mixed tumors. There was a significant difference in frequencies of CD44 variant expression between normal and cancerous tissues. Furthermore, lymph-vascular space involvement of cancer cells was observed to be statistically significant in the CD44-negative group as opposed to the positive group. Reverse transcription-polymerase chain reaction and Southern blot hybridization clearly demonstrated that normal endometrial tissues express the standard CD44 form as well as the variant form. Immunohistochemical examination of normal endometrium revealed that intense staining was seen on the gland cells at the basement membrane side, and less intense staining was seen between the gland cells. These results suggest that CD44 could play important roles in the function of normal endometrium and that reduced CD44 expression might be related to the metastasis of endometrial cancer cells through lymph-vascular space.

Transferrin facilitates the formation of DNA double-strand breaks via transferrin receptor 1: the possible involvement of transferrin in carcinogenesis of high-grade serous ovarian cancer.

Fallopian tubal epithelium is a candidate for the origin of high-grade serous ovarian cancer. Transferrin-containing follicular fluid and/or retrograde menstrual blood are possible risk factors for carcinogenesis. Accumulation of DNA double-strand breaks (DNA-DSBs) in the fallopian tubal epithelium is considered to play an important role in the development of cancer. However, the mechanisms by which DNA-DSBs accumulate have not yet been fully elucidated. The hydroxyl radical, which is produced in a Fenton reaction catalyzed by an iron ion, serves as a potent DNA-DSB-inducing molecule, raising the potential of an iron ion transporter of transferrin in the formation of DNA-DSBs. We studied the potential involvement of transferrin in DNA damage and the development of ovarian cancer. Treatment with transferrin facilitated the formation of histone 2AX phosphorylated at Serine 139 (γH2AX), which is known as a DNA-DSB marker, in human fallopian tube secretory epithelial cells and A2780 ovarian cancer cells. Knockdown of transferrin receptor 1 (TfR1), but not transferrin receptor 2, suppressed the transferrin uptake and consequent formation of γH2AX. As hydroxyl radicals in reactive oxygen species (ROS) are involved in DNA-DSBs, the formation of ROS was determined. Treatment with TfR1-specific small interference RNAs significantly diminished transferrin-induced formation of ROS. Moreover, TfR1-dependent uptake of transferrin was revealed to augment the formation of DNA-DSBs in the presence of hydrogen peroxide, which served as a substrate for the Fenton reaction. An ex vivo study with murine fallopian tubes further demonstrated that transferrin treatment introduced DNA-DSBs in the fallopian tubal epithelium. Collectively, these data suggested that the transferrin-TfR1 axis accounts for the induction of DNA-DSBs that potentially lead to DNA damage/genome instability. These findings also suggested that exposure to transferrin initiates and promotes the development of ovarian cancer by aiding the accumulation of DNA-DSBs in the fallopian tubal epithelium.

Ceramide limits phosphatidylinositol-3-kinase C2ß-controlled cell motility in ovarian cancer: potential of ceramide as a metastasis-suppressor lipid.

Targeting cell motility, which is required for dissemination and metastasis, has therapeutic potential for ovarian cancer metastasis, and regulatory mechanisms of cell motility need to be uncovered for developing novel therapeutics. Invasive ovarian cancer cells spontaneously formed protrusions, such as lamellipodia, which are required for generating locomotive force in cell motility. Short interfering RNA screening identified class II phosphatidylinositol 3-kinase C2ß (PI3KC2ß) as the predominant isoform of PI3K involved in lamellipodia formation of ovarian cancer cells. The bioactive sphingolipid ceramide has emerged as an antitumorigenic lipid, and treatment with short-chain C6-ceramide decreased the number of ovarian cancer cells with PI3KC2ß-driven lamellipodia. Pharmacological analysis demonstrated that long-chain ceramide regenerated from C6-ceramide through the salvage/recycling pathway, at least in part, mediated the action of C6-ceramide. Mechanistically, ceramide was revealed to interact with the PIK-catalytic domain of PI3KC2ß and affect its compartmentalization, thereby suppressing PI3KC2ß activation and its driven cell motility. Ceramide treatment also suppressed cell motility promoted by epithelial growth factor, which is a prometastatic factor. To examine the role of ceramide in ovarian cancer metastasis, ceramide liposomes were employed and confirmed to suppress cell motility in vitro. Ceramide liposomes had an inhibitory effect on peritoneal metastasis in a murine xenograft model of human ovarian cancer. Metastasis of PI3KC2ß knocked-down cells was insensitive to treatment with ceramide liposomes, suggesting specific involvement of ceramide interaction with PI3KC2ß in metastasis suppression. Our study identified ceramide as a bioactive lipid that limits PI3KC2ß-governed cell motility, and ceramide is proposed to serve as a metastasis-suppressor lipid in ovarian cancer. These findings could be translated into developing ceramide-based therapy for metastatic diseases.

Complete androgen insensitivity in a 47,XXY patient with uniparental disomy for the X chromosome.

We describe a unique patient with complete androgen insensitivity syndrome and a 47,XXY karyotype. Androgen receptor assay using cultured pubic skin fibroblasts showed no androgen-binding capacity. Sequence analysis of the androgen receptor gene demonstrated two nonsense mutations, one in exon D and one in exon E. Microsatellite marker analysis showed that the patient is homozygous for all five Xq loci examined. The results suggest that the long-arms of the two X chromosomes are identical, i.e., uniparental isodisomy at least for Xq, and carry the same mutations in the androgen receptor gene. This explains how complete androgen insensitivity syndrome occurred in this 47,XXY individual.

Menstrual cycle dependent expression of CD44 in normal human endometrium.

CD44 is a cell surface glycoprotein known to be a hyaluronate receptor, which functions in lymphocyte homing and cancer metastasis. We have previously shown that CD44 molecules are expressed in normal endometrial tissue. In this study we immunohistochemically examined expression of CD44 glycoproteins in normal human endometrial tissue to gain insight into roles of CD44 molecules. No expression of the CD44 standard form was observed with 11 endometria in the proliferative phase. On the contrary, 13 of 19 secretory phase endometria were stained intensely by anti-CD44 standard form anti-body; all CD44-positive cases were in the mid and late secretory phases. Among the 13 CD44-positive endometria, four also were positive for the CD44 variant with exon v6. CD44 molecules were present at all but the luminal cell surfaces. These results indicate that expression of CD44 depends on menstrual cycle, suggesting that CD44 molecules might be involved in implantation of fertilized ovum in endometrium.

Growth pattern of twins of different chorionicity evaluated by sonographic biometry.

OBJECTIVE: To determine differences between growth patterns of monochorionic and dichorionic twins, and of concordant and discordant twins of both chorionicities. METHODS: We studied 70 cases of concordant twins (24 monochorionic, 46 dichorionic) and 45 cases of discordant twins (25 monochorionic, 20 dichorionic). In each case, growth was measured longitudinally by ultrasound biometry and the growth pattern was depicted. RESULTS: There were no differences in incremental growth between concordant monochorionic and dichorionic twins. The growth curve of concordant twins of both chorionicities was almost the same as that of a singleton until 34 weeks' gestation. However, in the discordant twins, the growth of the larger twin matched the growth curve of a singleton or concordant twin, but the growth of the smaller twin gradually decreased to the range of growth restriction. The growth curves for monochorionic discordant twins appeared to be representative of two groups, one of which had onset of discordancy before 24 weeks. CONCLUSION: It is clinically important to determine chorionicity early in twin pregnancies, to calculate the percentage of discordancy between the fetuses, and to examine longitudinal fetal growth curves in each chorionicity.

SRY mutation and tumor formation on the gonads of XP pure gonadal dysgenesis patients.

We report three patients with XY pure gonadal dysgenesis. Two of these patients developed gonadoblastoma and associated dysgerminoma. Molecular analyses were undertaken to investigate the relationship between the formation of these tumors and Y chromosome aberrations. Deletion analyses were performed by polymerase chain reaction (PCR) amplification of Y chromosome-specific DNA sequences (PABY, SRY, DYS250, DYS254, and DYZ1). A cryptic deletion of the short arm of the Y chromosome that included the PABY, SRY, DYS250, and DYS254 loci was observed in one of the patients (22-years-old) with an associated tumor. In the other two patients who did not demonstrate such a deletion, the sequence of the SRY open reading frame was determined by the dideoxynucleotide method. Two nucleotide substitutions followed by a seven nucleotide deletion were observed in the 3' end of HMG (high mobility group)-box in the other patient (15-years-old) with an associated tumor. The patient (22-years-old) without an associated tumor did not have the cryptic deletion or mutation of SRY. A Y chromosome specific sequence (DYZ1) was demonstrated by PCR amplification of microdissected tumor tissues from these two patients. These results suggest that SRY may play a role in the formation of gonadal tumors, especially dysgerminoma.

Enzyme-linked immunosorbent assay for IgG and IgM antibodies against human parvovirus B19: use of monoclonal antibodies and viral antigen propagated in vitro.

Enzyme-linked immunosorbent assay (ELISA) systems for serum IgG and IgM antibodies to human parvovirus B19 were established by utilizing anti-B19 monoclonal antibodies (mAbs) and human plasma B19 antigen. The specificities of IgG and IgM ELISA were confirmed by indirect immunofluorescence staining and Western blot immunoassay with panel sera. The series of serum specimens obtained from two B19-infected patients were examined with ELISA. The IgM antibody titers increased quickly after the onset of the symptoms and returned to a negative range after five months. The IgG antibody titers also increased just after the increasing of IgM titers and the elevated levels continued for more than a year. We also established the same ELISA systems by utilizing in vitro propagated B19 antigen and similar results were obtained.

A study by means of a new assay of the relationship between an outbreak of erythema infectiosum and non-immune hydrops fetalis caused by human parvovirus B19.

An enzyme-linked immunosorbent assay (ELISA), used to detect IgG and IgM antibody specific for human parvovirus B19, was established by use of human parvovirus B19 capsid protein VP-1 expressed in Escherichia coli. Paired samples of serum derived from 44 mothers and single samples derived from 24 babies having unexplained non-immune hydrops fetalis (NIHF), were tested by means of the assay. Five cases (11%) of NIHF were suspected of having been induced by intrauterine human parvovirus B19 infection because the samples of maternal serum were positive for parvovirus B19 IgM antibody. Four of the five cases arose during an outbreak of erythema infectiosum. According to our study and previous reports over 90% of NIHF caused by parvovirus B19 intrauterine infection have become clinically overt in the second trimester of pregnancy during a period ranging from 15 to 27 weeks of gestation.

Serologic study of human parvovirus B19 infection in pregnancy in Japan.

OBJECTIVES: To clarify the relationship between hydrops fetalis and parvovirus outbreaks in the community, seroprevalence of B19 antibody among women of childbearing age, and adverse effects of intrauterine B19 infection. METHODS: Sera were collected from 168 cases of hydrops fetalis which were diagnosed between 1987 and 1997 in Miyagi prefecture, Japan, from 232 healthy pregnant women in 1987 and 277 healthy pregnant women in 1997 in Miyagi, and from 48 women infected with B19 during pregnancy. The sera were examined for B19 IgG and IgM antibodies by enzyme-linked immunosorbent assay and for B19 DNA by polymerase chain reaction. The number of cases of erythema infectiosum in Miyagi had been monitored each month. RESULTS: Thirteen of the 168 cases of hydrops fetalis were found to be caused by intrauterine B19 infection and 12 of the 13 cases clustered in two periods of outbreaks of erythema infectiosum in the community. The positive rates of B19 IgG antibody between 1987 and 1997 were significantly different: 33% in 1987 and 46% in 1997. Nine of the 48 women infected during pregnancy showed adverse effects of the fetus: eight hydrops fetalis and one early abortion with positive B19 DNA. The fetal death rate (>12 weeks of gestation) among them was 15% (7/48), far higher than the calculated 1% among the general population. The nine mothers with adverse fetal outcomes had contact with the infectious source at the 16 weeks of gestation or earlier. CONCLUSIONS: These data clearly showed a relationship between hydrops fetalis and parvovirus outbreaks in the community, and it may be important to follow the seroprevalence for an extrapolated period time to predict occurrence of hydrops fetalis caused by B19. Also the data indicated that the gestational week infection occurred is the most important determinant of an adverse effect to the fetus as described previously.