A Subset of Patients With Recurrent Spontaneous Abortion Is Deficient in Transforming Growth Factor β-2-Producing “Suppressor Cells” in Uterine Tissue Near the Placental Attachment Site

PROBLEM : To determine if patients with unexplained recurrent miscarriage have a deficiency of decidual immunosuppressor cells that produce transforming growth factor β type 2, as has been found in mice with abortion due to rejection and/or trophoblast failure. METHODS : Decidual biopsy specimens were taken as near to the placental attachment site as possible under ultrasound guidance from first trimester legal termination (control) patients with recurrent miscarriage and non-viable pregnancy, and from patients with sporadic missed abortion. The tissue was tested for TGFβ-2⁺ suppressor cells by in situ hybridization, immunohistochemistry, and analysis of supernatants. RESULTS : TGFβ-2-related suppressor molecules similar but not identical to those identified in pregnant mice were released by decidual lymphoid cells. Fifty percent of 14 recurrent miscarriage patients showed a lack of suppressor cells and 59% were subnormal in comparison to 20 controls and 5 sporadic miscarriage patients, where 80–85% of the patients had detectable suppressor cells. CONCLUSIONS : Suppressor cell deficiency is compatible with a role for rejection and/or trophoblast failure in some patients with recurrent miscarriage. Presence of suppressor cells in most patients with missed abortion (4/5) is compatible with an alternative cause of fetal death, similar to findings reported in genetic fetal death mice.     

Basic Amino Acids Predominate in the Sequential Autoantigenic Determinants of the Small Nuclear 70K Ribonucleoprotein

Autoantibodies binding the 70K nRNP polypeptide are commonly found in the serum of patients with systemic lupus erythematosus. IgG antibodies binding overlapping octapeptides of 70K nRNP have been evaluated in 10 patients with anti-nRNP precipitins, seven patients with other autoimmune serology, and four normal human sera. Neither normal controls nor patients without an anti-nRNP precipitin significantly bind any of the 70K nRNP octapeptides. Sera containing an anti-nRNP precipitin strongly bind various combinations of eleven different regions of the 70K nRNP protein. One antigenic region is consistently the most reactive in nine often nRNP precipitin positive sera tested. This sequence, KDKDRDRKRRSSRSR, is highly charged and has a similar pattern of alternating basic amino acids also present in seven of the other purported humoral autoimmune epitopes of the 70K nRNP polypeptide. The closely related DRKR and ERKR are important components of two of these epitopes. All regions of the 70K peptide bound by human anti-nRNP precipitin positive sera are very rich in the basic amino acids., especially lysine (chi-square = 23.03, odds ratio = 13.3, P <0.000001).     

The Effect of the Nitrite Ion on Intact Human Erythrocytes

The mode of action of the nitrite ion on intact human erythrocytes has beeninvestigated under varying experimental conditions. Nitrite appeared to actdirectly to cause methemoglobin formation and GSH depletion. Evidencewas presented to show that such depletion does not occur in the presence ofa normal and active pentose phosphate pathway, and to suggest that methemoglobin formation buffers the erythrocyte against nitrite-induced oxidationof GSH.

Both in the presence and absence of glucose, nitrite in high concentrationwas found to cause increased rates of oxidative destruction of hemoglobinwith Heinz body formation, and of loss of osmotic integrity. It was suggestedthat nitrite acts by "simple" oxidation of the -SH groups of globin and othererythrocytic components, and possibly by causing deamination of cellularproteins.

The results were discussed, with reference to the significance of cellularprotective mechanisms under evolutionary or environmental conditions whichinvolve intermittent exposure to high concentrations of the nitrite ion.

Submitted on February 6, 1962 Accepted on July 3, 1962     

Diabetic retinopathy in pregnancy

Summary. The records of 23 insulin-dependent diabetics who had serial ophthalmological examinations during pregnancy and afterwards were reviewed. Fourteen pregnancies occurred in 10 patients with no retinopathy; 30% of these patients had obstetric complications. The mean birthweight was 3.5 kg. Ophthalmological status was unchanged in this group. In eight patients with background retinopathy during 10 pregnancies the obstetric complication rate was 70% and mean birth-weight 3.3 kg. During pregnancy there was no evidence of progression of retinopathy. One patient developed proliferative retinopathy 4 years later. Five patients had proliferative retinopathy. The mean age (32 years) and duration of diabetes at index pregnancy (18 years) was greater than for the other groups. All patients developed pre-eclampsia and mean birthweight was 2.8 kg. Four of these patients required argon laser photocoagulation in association with pregnancy for progressive retinopathy; one died subsequently from end-stage diabetic nephropathy; the other four have maintained their pre-pregnancy visual acuity from 4 to 10 years.     

Is centralized hospital care necessary for all insulin-dependent pregnant diabetics?

Summary. A retrospective population study in Northern Ireland examined the benefits of centralized care in insulin-dependent diabetic pregnancies. In the 5 years 1979–1983, there were 139 250 deliveries in Northern Ireland and of these 221 pregnancies occurred in 187 insulin-dependent diabetic patients; 100 were managed entirely in peripheral maternity units, 61 were referred from a peripheral unit to the Royal Maternity Hospital, Belfast and 60 were managed entirely in this central referral hospital. The patients referred from the periphery had the worst past obstetric history with a combined perinatal mortality rate of 200 per 1000. During the study period the perinatal mortality rate was 107 for the referred pregnancies, 33 for those managed entirely in the peripheral units and 18 for those managed at the Royal Maternity Hospital. If those pregnancies terminated for fetal abnormality, and deaths beyond the perinatal period are included, the figures for total fetal loss were 15.5%, 5.5% and 7.1% respectively. Overall the major congenital malformation rate was 7.5%, and for the respective groups 6.5%, 3.0% and 13.0%. For the general population during the same period the perinatal mortality rate was 1.4% and the major congenital malformation rate was 2.5%. Thus it is suggested that only peripheral hospitals which can offer combined antenatal/endocrine care and with a neonatal intensive care unit should undertake the management of the pregnant diabetic.