Measurement of bone mineral density of lumbar spine and whole body in low-birth-weight infants: comparison of two methods.

In the present study, we compared lumbar spinal and whole-body bone mineral density (BMD) measurements to determine which is more suitable for evaluating the bone mineral status of low-birth-weight (LBW) infants. Lumbar spinal and whole-body BMD were assessed simultaneously in a prospective series including 152 Japanese LBW infants (birth weight 453-2400 g, gestational age 24-38 weeks) from the age of 40 weeks post-conception to 2 years of age. Lumbar spinal BMD at 40 weeks post-conception was significantly correlated with birth weight (r = 0.74; P < 0.0001), but wholebody BMD was not correlated with birth weight. No correlation was found between lumbar spinal and whole-body BMD at 40 weeks post-conception. However, after 40 weeks post-conception, a significant correlation was found between lumbar spinal and whole-body BMD (r = 0.65; P < 0.0001). For infants with a body weight of 4 kg or less at the time of measurement, no correlation was found between lumbar spinal and whole-body BMD. However, for infants with a body weight above 4 kg, a significant correlation was found between lumbar spinal and whole-body BMD (r = 0.65; P < 0.0001). Thus, lumbar spinal BMD is more suitable than whole-body BMD for evaluation of the bone mineral status of LBW in early infancy. Therefore, lumbar spinal BMD should be used for serial evaluation of changes in the bone mineral status of LBW infants.

Bone mineral density of the lumbar spine in very-low-birth-weight infants: a longitudinal study.

UNLABELLED: To examine osteopenia in very low birth weight (VLBW) infants we used repeated dual-energy X-ray absorptiometry in a prospective study of lumbar spinal bone mineral density (BMD) in Japanese VLBW infants (birthweight 426-1498 g; n = 61, group 1) aged 40 weeks postconception to 3 years of age. Control subjects were Japanese infants with birthweight 1500-1999 g (group 2), 2000-2499 g (group 3), or more than 2500 g (group 4). BMD in group 1 during the early period after birth was very low, increased rapidly for 1 year, and then gradually increased until 3 years of age (r = 0.931, P < 0. 0001). BMD at the age of 40 weeks postconception was 0.085 +/- 0.026, 0.132 +/- 0.039, 0.178 +/- 0.042, and 0.196 +/- 0.046 g/cm(2) in groups 1, 2, 3, and 4, respectively (P < 0.0001). However, at 1 and 2 years of age no differences were observed among the groups in BMD. CONCLUSION: This study shows that lumbar spinal BMD in VLBW infants can normalize by the age of 2 years.

Novel mutations, including the second most common in Japan, in the beta-hexosaminidase alpha subunit gene, and a simple screening of Japanese patients with Tay-Sachs disease.

Two novel mutations of the beta-hexosaminidase alpha subunit gene were identified in Japanese patients with the infantile form of Tay-Sachs disease. One mutation was a one-base deletion at nt613C, which generated a stop codon at two codons downstream, in three unrelated patients. The other mutation was a one-base substitution of G-to-A at IVS 5, +1, which caused a splicing abnormality, in one patient. A missense mutation of R170W, which has already been reported in other ethnic groups, was also newly identified in one patient. In 1993, the most common mutation (IVS 5, -1G-->T) in Japanese patients with Tay-Sachs disease was reported as the major mutation in Japan accounting for 80% of 56 mutant alleles from 28 unrelated patients. The deletion of nt613C was the second most common mutation, accounting for 5% of the mutant alleles. The previously reported mutation IVS 5, -1G-->T and the nt613C deletion found in this study together accounted for 85% of the mutations causing Tay-Sachs disease among Japanese. Since these two mutations were located in or close to exon 6 and since they abolish Fok I (IVS 5, -1G-->T) and Sfa NI (nt613C deletion) restriction sites, respectively, they were screened rapidly by single polymerase chain reaction followed by digestion with these enzymes.

Two mutations remote from an exon/intron junction in the beta-hexosaminidase beta-subunit gene affect 3'-splice site selection and cause Sandhoff disease.

Four unrelated Japanese patients with infantile Sandhoff disease (beta-hexosaminidase beta-subunit deficiency) have been studied for the molecular basis of their severe phenotype. Two patients had complex base substitutions; one patient was homoallelic for a triple mutation (P417L, K121R, and S255R) and the other was a compound heterozygote of a double (P417L and K121R) mutation and the triple mutation. K121R is known to be a functional polymorphism, while P417L (exon 11, +8 C-->T) generates predominantly an abnormally spliced mRNA at base +112 of exon 11 and has been described in two patients with a juvenile form of the disease. The mild phenotype is attributed to the presence of a small amount of normally spliced mRNA. S255R is a novel mutation without prior description in the literature. An expression study of the normally spliced cDNA with the double and the triple mutations gave about 70% and 30% of normal activity, respectively. This finding suggests that S255R further reduces the catalytic activity of the already below-threshold amount of normally spliced mRNA and accounts for the more severe phenotype in our patients. In the other two patients, a novel disease-causing base transition was found within intron 10, away from the intron/exon junction (-17 a-->g). This mutation caused abnormal 3' splicing at position -37 of intron 10, and no normally spliced product was detectable upon RT-PCR analysis. We noted an unusually low splice site score (61.8) for the exon 10/intron 11 junction and suspected that this might be partially responsible for the aberrant splicing in these mutations. To test this hypothesis, we constructed four chimeric cDNAs all with an additional intron 10 inserted and evaluated their splicing efficiency. They, respectively, had the normal sequence, P417L (exon 11, +8 C-->T), the intronic mutation (-17 a-->g), and the intronic mutation with an artificially engineered intron 10/exon 11 junction of a higher splice site score (85.1). Of the total transcripts, 67% and 32% were correctly spliced in the normal chimeric construct and P417L, respectively, while no normally spliced product was generated either in the chimeric construct with -17 a-->g or in that with a high splice site score. The sequence around the adenosine -17 residue upstream of the normal acceptor splice site in this report, UGCAAU (-21 to -16), matches the consensus branchpoint sequence YNYRAY (Y, pyrimidine; R, purine; N, any base) reported in the literature. The mutation in this study is most likely to abolish lariat formation because the artificial site of the high splice site score did not improve splicing efficiency.

[Double negative adult T-cell leukemia with hemophagocytic syndrome].

A 79-year-old woman was admitted with general fatigue, jaundice and hepatosplenomegaly. Perpheral blood examination showed 8.0 g/dl Hb, 15 x 10(3)/microliter platelet and 10,490/microliter leukocytes with 86% abnormal lymphocytes. Immunophenotypic analysis of abnormal lymphocytes demonstrated CD2(+), CD3(+/-), CD4(-), and CD8(-). Serum antibody for HTLV-1 was positive. In addition, the monoclonal integration of HTLV-1 proviral DNA into the genome of leukemic cells was demonstrated on Southern blot hybridization. Bone marrow revealed ATL cell in vasion with myelofibrosis and hemophagocytic cell proliferation. Therefore, adult T-cell leukemia with hemophagocytic syndrome was diagnosed. She was treated with methyl prednisolone pulse therapy and gammaglobulin. But she died of hepatic failure 14 days after hospitalization. On autopsy, EB virus LMP-1 was detected in ATL cells in bone marrow. ATL with hemophagocytosis is relatively rare. The association of both pathological states was discussed.

[A case of prostatic adenocarcinoma with pulmonary metastases--diagnosis by transbronchial lung biopsy and immunohistochemistry].

Metastatic pulmonary adenocarcinoma was found in a 79-year-old man, who had symptoms of general malaise and poor appetite. An extensive work-up including a transurethral resection of the prostate, failed to establish the primary site of the malignancy. By administering chlormadinone acetate for prostatic hypertrophy, the pulmonary metastases improved dramatically. The tumor cells in the lung, which had previously been obtained by transbronchial lung biopsy, stained positive for prostatic acid phosphatase and prostatic specific antigen. These data suggested that prostatic carcinoma had metastasized to the lung. The prostatic carcinoma was finally confirmed at autopsy.