18q Deletion Syndrome Presenting with Late-Onset Combined Immunodeficiency.

Patients with chromosome 18q deletion syndrome generally experience hypogammaglobulinemia. Herein, we describe two patients with chromosome 18q deletion syndrome who presented with late-onset combined immune deficiency (LOCID), which has not been previously reported. Patient 1 was a 29-year-old male with 18q deletion syndrome, who was being managed for severe motor and intellectual disabilities at the Yamabiko Medical Welfare Center for 26 years. Although the patient had few infections, he developed Pneumocystis pneumonia at the age of 28. Patient 2, a 48-year-old female with intellectual disability and congenital malformations, was referred to Tokyo Medical and Dental University Hospital with abnormal bilateral lung shadows detected on her chest radiography. Computed tomography showed multiple lymphadenopathies and pneumonia. A lymph node biopsy of the inguinal region revealed granulomatous lymphadenitis, and a chromosomal examination revealed 18q deletion. Array-based genomic hybridization analysis revealed deletion at 18q21.32-q22.3 for patient 1 and at 18q21.33-qter for patient 2. Immune status work-up of the two patients revealed panhypogammaglobulinemia, decreased number of memory B cells and naïve CD4+ and/or CD8+ cells, reduced response on the carboxyfluorescein diacetate succinimidyl ester T-cell division test, and low levels of T-cell receptor recombination excision circles and Ig κ-deleting recombination excision circles. Consequently, both patients were diagnosed with LOCID. Although patients with 18q deletion syndrome generally experience humoral immunodeficiency, the disease can be further complicated by cell-mediated immunodeficiency, causing combined immunodeficiency. Therefore, patients with 18q deletion syndrome should be regularly tested for cellular/humoral immunocompetence.

Effects of pure 2,4-dichlorophenoxyacetic acid on cultured rat embryos.

2,4-dichlorophenoxyacetic acid (2,4-D), a plant growth regulator, has been used worldwide as a herbicide. Previously we evaluated the prenatal developmental effects of 2,4-D by feeding it to pregnant rats and found that it is maternally toxic and embryolethal, and it induces urogenital malformations in rat fetuses. In the study presented here, we investigated the effects of pure 2,4-D on rat embryos in whole embryo culture. Rat embryos on day 9.5 of gestation were cultured for 48 h at several concentration levels with pure 2,4-D (50-500 microg/mL). 2,4-D caused a concentration-related increase in the incidence of each malformation. Significant decreases in the number of somites were observed at a concentration of 100 microg/mL or more. At the concentration of 100 microg/mL, there was normal yolk sac circulation. This result suggests that 2,4-D has a detrimental effect on somite development and directly damages developing embryos.

Effects of supplemental L-methionine on E-64 [trans-epoxysuccinyl-1-leucyl-amido (4-guanido) butane]-induced dysmorphology in rat embryos cultured in vitro.

E-64 [trans-epoxysuccinyl-1-leucyl-amido (4-guanido) butane] is teratogenic, inducing a spec-trum of malformations in vivo and producing similar effects in vitro. Numerous studies support the concept that E-64-induced malformations result from embryonic nutritionaldeficiency, without affecting the maternal nutritional status. This has provided a useful model with which to investigate the nutritional requirements of the early embryo, as well as the role of various nutrients in the etiology of congenital defects. In the current investigation, we examined effects of L-methionine on E-64-induced embryotoxicity in vitro. For these experiments, we cultured rat embryos 9.5 days postconception (p.c.) for 48 hours with E-64 and/or L-methionine. We found that the addition of L-methionine to E-64-exposed cultures reduced optic abnormality and increased embryo protein. These results suggest that embryopathy largely results from a deficiency of L-methionine although E-64 limits the supply of all amino acids to the embryo. Furthermore, although endocytosis and degradation of proteins by the visceral yolk sac (VYS) supply most amino acids to the embryo, free amino acids may be compensatory when this source is reduced. These results support those of previous investigations that suggest L-methionine is a limiting nutrient for embryonic development.

Postnatal survival of rat offspring prenatally exposed to pure 2,4-dichlorophenoxyacetic acid (2,4-D).

In previous report on prenatal developmental effects of pure 2,4-dichlorophenoxyacetic acid (2,4-D) in rat, we found that this chemical was maternally toxic, embryolethal, and that it induced urogenital malformations in the fetuses. In the present report, we investigated the postnatal survival of the offspring prenatally exposed to 2,4-D during organogenesis, to determine the participation of urogenital malformations on postnatal survival. We used doses of 70 mg, 110 mg and 150 mg, which were each found to induce significant urogenital malformations, when administered in different periods of organogenesis: GD 6 to 15, GD 6 to 10, and GD 11 to 15. We found that 2,4-D has a significant influence on progeny viability by increasing the postnatal death. The kidney and urinary tract malformations induced in the fetuses might be the cause of the increased rate of postnatal death. 2,4-D did not impair the postnatal growth of the unaffected offspring.