Alfonso J. Herruzo

High frequency of altered HLA class I phenotypes in invasive breast carcinomas

We studied 105 tumor samples obtained from patients diagnosed as having breast carcinomas for HLA class I and II (DR) antigen expression, using a panel of mAbs defining HLA-monomorphic, locus-specific and allele-specific determinants. Peripheral blood lymphocytes from patients were also typed for HLA alleles. The results indicated total HLA class I losses in 55 patients (52.3%), HLA-A locus losses in four patients (3.8%), HLA-B locus losses in eight patients (7.6%), and A, B, locus losses in 10 patients (9.5%). The remaining 28 patients whose tissues reacted positively with monomorphic- and locus-specific mAbs were tested for HLA allelic losses using several anti-HLA mAbs defining A2, A3, A9, B8, B12, etc. Of these 28 patients, 16 (57%) showed one or more losses of HLA reactivity. These results indicated that in 88.5% of patients we detected a particular HLA-altered tumor phenotype. The downregulation of HLA class I antigens in breast carcinomas may thus be more frequent than previously reported, and patients without HLA class I downregulation may be the exception rather than the rule. It cannot be ruled out that HLA alterations are present in some of the 12 patients with an apparently normal HLA phenotype, as some HLA alleles could not be studied because of the lack of appropriate mAbs. These HLA alterations could represent an important step associated with tumor invasion, conferring to the tumor cells the ability to escape from T-lymphocyte recognition.

Mononuclear cell subpopulations in human follicular fluid from stimulated cycles.

ABSTRACT: The study of lymphocyte subsets from human follicular fluid (FF) provides an opportunity to evaluate immunological features of the ovary. We investigated the mononuclear cell subsets in FF and peripheral blood obtained at the time of laparoscopy from ten in vitro fertilization (IVF) patients. Midcycle nonpregnant peripheral blood was used as the control. A marked increase in the proportion of monocytes (CD14+) was observed in FF. Although FF was enriched with CD8+ lymphocytes, a decrease in the proportion of CD4+ lymphocytes was observed. “Memory” T cells in FF, identified by the CD4+ CD45R− phenotype, predominated over “naive” T cells (CD4+ CD45R+) at a ratio of 2:1, which differs from the ratio yielded by control blood samples (1:1). The percentage of activated T cells (CD3+ HLA‐DR+ cell) increased significantly in FF. When lymphocyte subsets were studied in the peripheral blood of IVF patients, changes similar to but less significant than those in FF were found. These data support the concept that lymphocytes play an important role in ovarian physiology.

Amnioinfusion in term labor with low amniotic fluid due to rupture of membranes: a new indication.

OBJECTIVE The null hypothesis was that the use of intrapartum amnioinfusion to induce term labor because of premature rupture of membranes when labor was complicated by low amniotic fluid volume due to vaginal loss would not improve fetal heart rate patterns, decrease the incidence of operative delivery, or improve neonatal acid-base status. STUDY DESIGN 200 term pregnancies with low amniotic fluid due to vaginal loss were randomly chosen to receive intrapartum amnioinfusion or standard obstetric care without amnioinfusion. Fetal heart rate pattern, method of delivery and neonatal acid-base status were compared with Students t test, chi-squared analysis, Mann-Whitney U- or Fishers exact test. RESULTS When amnioinfusion was used, the fetuses had lower rates of variable (74 vs. 91%, P<0.01) or late (26 vs. 58%, P<0.001) decelerations. Spontaneous deliveries were more frequent (77 vs. 59%, P<0.01) and cesarean sections less frequent (3 vs. 10%, P<0.05). Mean umbilical arterial (7.24+/-0.07 vs. 7.21+/-0.08, P<0.01) and venous (7.31+/-0.06 vs. 7.28+/-0.08, P<0.01) pH were significantly higher in newborns with amnioinfusion, and babies in this group had lower rates of neonatal acidemia of arterial (22 vs. 36%, P<0.005) or venous (13 vs. 26%, P<0.005) origin. CONCLUSIONS Amnioinfusion improved fetal heart rate pattern, lowered the incidence of operative delivery, and improved neonatal acid-base status in term labor complicated by low amniotic fluid due to vaginal loss.

Luteal cytoplasmic estradiol and progesterone receptors in human endometrium: in vitro fertilization and normal cycles

Luteal cytoplasmic estradiol (E2) and progesterone (P) receptor levels were measured from the 22nd to the 25th days of the menstrual cycle in endometrial samples obtained from seven patients in an in vitro fertilization (IVF) program who received no embryo replacement after ovarian stimulation with clomiphene citrate/human menopausal gonadotropin/human chorionic gonadotropin, and from seven normally menstruating women. Serum levels of E2, P, follicle-stimulating hormone, luteinizing hormone, and prolactin (PRL) were measured in blood samples collected at the time of biopsy. The E2 (P

Influence of obstetric and perinatal care on perinatal mortality

OBJECTIVE Cases of perinatal death attributed to suboptimal perinatal care between 1979 and 1992 inclusive at a large, tertiary care center are reviewed. STUDY DESIGN The study compared two periods: 1979-1985 and 1986-1992. The perinatal morbidity-mortality committee analyzed patient records for the mothers and neonates, delivery room records, the results of fetal autopsy, and histological sections of the placenta. RESULTS In the first period, 21.5% of the deaths were found to have received suboptimal care; this figure declined 13.5% in the second period (P < 0.05). During the second period, antenatal, intranatal and postnatal care improved, as shown by the lower suboptimal care rate for antepartum (15.8% versus 9.8%; P < 0.05), intrapartum (49.2% versus 22.1%; P < 0.001) and postpartum death (19.9% versus 8.1%; P < 0.001). During both periods, fetal death during pregnancy made up the largest proportion of deaths attributed to suboptimal care, with 44 cases (43.1%) during 1979-1985, and 36 cases (64.3%) during 1986-1992 (P < 0.01). Of these cases, fetuses with intrauterine growth retardation were the most frequent recipients of suboptimal care (20 cases (45.5%) during the first period; 18 cases (50%) during the second period). CONCLUSION Despite better prenatal care, the highest suboptimal care rate was due to suboptimal care during pregnancy, when some high risk situations were overlooked by the obstetrician.

Follicular fluid α-fetoprotein, carcinoembryonic antigen, and CA-125 levels in relation to in vitro fertilization and gonadotropin and steroid hormone concentrations

OBJECTIVE To investigate the possible role of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and CA-125 in the ovarian follicle. DESIGN alpha-Fetoprotein, CEA, and CA-125 were measured in human follicular fluid (FF) and correlated to IVF outcome and gonadotropin and gonadal steroid hormones. SETTING The In Vitro Fertilization Program at Virgen de las Nieves Hospital, Granada, Spain. PATIENTS Thirty-six FF from 12 infertile women with irreparable tubal damage who underwent treatment for ovarian stimulation with clomiphene citrate, hMG, and hCG. INTERVENTIONS Laparoscopic follicular aspiration followed 48 hours later by ET. MAIN OUTCOME MEASURE Serum and FF AFP, CEA, and CA-125 levels. RESULTS alpha-Fetoprotein, CEA, and CA-125 were detected in all samples of serum and FF. There were no significant differences between the serum and FF levels. Follicular fluid AFP, CEA, and CA-125 of fertilized oocytes were similar to those in the unfertilized oocytes group. There were no significant correlations between the FF AFP, CEA, and CA 125 levels and gonadotropin and gonadal steroid hormone levels. CONCLUSIONS alpha-Fetoprotein, CEA, and CA-125 are present in FF after ovarian stimulation, but the mean intrafollicular levels do not differ significantly regardless of the outcome of oocyte IVF.

Immunosuppressive properties of human follicular fluid

Human preovulatory follicular fluids (FF) obtained in the course of stimulated cycles were analyzed for their possible immunologic functions. Different concentrations of FF (20%, 2%, 1%) inhibited the mitogenic response of normal human lymphocytes to concanavalin A (Con A). Lymphocytes were assessed for immunosuppressor activity after preincubation with FF. Lymphocyte mitogenic response to Con A was only suppressed by cells preincubated with FF at concentrations of 2% and 1% for at least 48 hours. No evidence of suppressor cell induction was seen following incubation of lymphocytes with 20% FF, nor was any significant relationship between FF immunosuppressor activity and the outcome of in vitro fertilization observed. We conclude that some factor(s) in FF may be capable of directly inhibiting lymphocyte response and inducing immunosuppressor cell activity in vitro.

Androgen producing luteinized granulosa cell tumor

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Lack of Expression of HLA Antigens on Immature Germ Cells From Ejaculates With Antisperm Antibodies

PROBLEM: The lack of expression of HLA antigen on immature germ cells from ejaculates with antisperm antibodies has been reported.

CD8+ lymphocyte subsets in human follicular fluid

In conclusion, we have shown that cells of the CD8 + CD11b + phenotype, characteristic of antigen-unspecific cytotoxic and suppressor cells, are the principal CD8 + subset detected in human FF