Yoshiro Tsuji

Prevalence of serum and salivary antibodies to HTLV-1 in Sjögren's syndrome

There is accumulating evidence that human T-lymphotropic virus-1 (HTLV-1) infection contributes to the development of various inflammatory disorders. To elucidate the relation between the infection and Sjögrens syndrome, seroepidemiological and virological studies were conducted on patients with this syndrome in Nagasaki Prefecture, Japan, an area heavily endemic for HTLV-1. The HTLV-1 seroprevalence rate among the patients with Sjögrens syndrome (17/74, 23%) was significantly higher than that among blood donors (916/27,284, 3%), whereas the difference between patients with systemic lupus erythematosus and blood donors was insignificant. Moreover, among Sjögrens syndrome patients the seroprevalence was high irrespective of age, unlike that among blood donors, which rose with age. Titres of serum antibodies in the HTLV-1 seropositive patients with Sjögrens syndrome were similar to those among patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and significantly higher than those among healthy carriers. IgM class antibodies were commonly detected in the serum of patients with Sjögrens syndrome. However, unlike that in HAM/TSP patients, the viral load in peripheral-blood mononuclear cells was not necessarily high in the seropositive Sjögren syndrome group. Salivary IgA antibodies to HTLV-1 were common among seropositive patients with Sjögrens syndrome (5/7), which might be due to increased viral activity in the salivary glands. These antibodies were barely detectable in HAM/TSP patients (prevalence 1/10) or in healthy carriers (0/11). The findings strongly suggest that HTLV-1 is involved in the pathogenesis of the disease in a subset of patients with Sjögrens syndrome in endemic areas.

Primary prevention of HTLV-I in Japan

The ATL prevention program (AAP) in the Nagasaki Prefecture since 1987 consists of screening of pregnant women and asking the seropositives to refrain from breast-feeding. We screened approximately 90% of gravidas in the Prefecture and > 90% of the seropositive women agreed not to breast-feed. The maternal transmission rate dropped from approximately 20% to approximately 3%. PCR of cord bloods showed that 2.5% were PCR-positive. However, among formula-fed children, none of the cord-positives seroconverted, and none of the seropositives tested had been cord-positive. Breast-feeding for less than six months decreased the transmission rate significantly, but may have a higher transmission rate than the formula feeding.

A Case of Neonatal McCune‐Albright Syndrome with Cushing Syndrome and Hyperthyroidism

ABSTRACT. We describe a female newborn infant with McCune‐Albright syndrome. In addition to the cutaneous pigmentation, she had apparent manifestations of hyperthyroidism and Cushing syndrome since birth. X‐ray examinations showed many scattered lucencies in multiple bones. Endocrinological findings were as follows: serum T4 276 nmol/l; free T4 125 pmol/l; TSH <1 mU/l; serum cortisol >2210 nmol/l; plasma ACTH < 10 pg/ml; urinary free cortisol 865 nmol/day; estradiol 0.36 nmol/l. Regardless of treatment with antithyroid drugs and an inhibitor of 3β‐hydroxysteroid dehydrogenase, the patient died of cardiac failure at the age of 4 months. Autopsy findings included a follicle cyst in the right ovary and multinodular hyperplasia in the thyroid and both adrenals. To our knowledge such a severe neonatal form of McCune‐Albright syndrome has not been described in the literature.

Rarity of PIT1 involvement in children from Russia with combined pituitary hormone deficiency

To ascertain the molecular background of combined pituitary hormone deficiency, screening for mutations in the pituitary-specific transcription factor (Pit-1/GHF-1) gene (PIT1) was performed on a cohort of 15 children from Russia with combined growth hormone (GH)/prolactin (Prl)/thyroid-stimulating hormone (TSH) deficiency. The group of patients, suspected of PIT1 mutations, consisted of four familial cases (seven patients) and eight sporadic cases. All had complete GH deficiency and complete or partial Prl and TSH deficiency. Direct sequencing of all six exons of PIT1 and its promoter region showed a C to T transition mutation at codon 14 of exon 1 in a 3 8/12-year-old girl. This novel PIT1 mutation results in a proline to leucine substitution (P14L). The patient was heterozygous for mutant and normal alleles. The heterozygous P14L mutation was also present in her mother as well as in her maternal aunt and grandmother, all of whom were phenotypically normal. There was no mutation in the fathers DNA, suggesting the need for reevaluation of genomic imprinting. In other children of our series, no mutation in PIT1 or in its promotor region was identified. This is the first report on the analysis of PIT1 and its promoter region in Russian children with GH/Prl/TSH deficiency. However, as the involvement of PIT1 mutation is rare in Russia, the other negative cases need to be analyzed for another candidate gene responsible for combined GH/Pr/TSH deficiency.

Maternal Transmisson of HTLV-1 Other than through Breast Milk: Discrepancy between the Polymerase Chain Reaction Positivity of Cord Blood Samples for HTLV-1 and the Subsequent Seropositivity of Individuals

We used a nested polymerase chain reaction (PCR) to diagnose HTLV‐1 carriers. The DNA isolated from the nuclear extract obtained from frozen whole blood was found appropriate for PCR study both qualitatively and quantitatively. The use of freshly frozen whole blood made the field work much easier, and the use of a nuclear extraction procedure allowed DNA isolation in just 4 microcentrifuge tubes. We could not attain sufficient sensitivity to detect a single molecule with single‐step PCR, but nested PCR was confirmed to detect a single molecule/reaction. All samples of the seropositive group including 94 blood donors, 66 mothers, and 13 children were positive in the nested PCR, while none of the seronegative group, including 198 blood donors and 285 children, was positive. Although 18/717 (2.5%) cord blood samples obtained from babies born to carrier mothers were PCR‐positive, none of 5 formula‐fed children tested who had been PCR‐positive in the cord blood gave evidence of infection later on. Furthermore, all of 4 seropositive infected children who were formula‐fed had been PCR‐negative in their cord blood. The results are not consistent with intrauterine infection, but suggest the presence of a perinatal or postnatal infection route other than through breast milk.

Cytogenetic evidence for partially committed myeloid progenitor cell origin of chronic myelomonocytic leukaemia and juvenile chronic myeloid leukaemia: both granuloctye-macrophage precursors and erythroid precursors carry identical marker chromosome

Summary. We used a micromethod for cytogenetic analysis from single haematopoietic colonies to study two adults with chronic myelomonocytic leukaemia (CMML) and a boy with juvenile chronic myeloid leukaemia (JCML) carrying distinct chromosome abnormalities, 7q—, der(21), and trisomy 21. We wanted to know if both granulocyte‐macrophage (GM) and erythroid precursors are involved in the abnormal clone. In all three patients, their chromosome abnormality was seen in almost all metaphases obtained from GM‐colonies and erythroid bursts. Peripheral blood leucocytes stimulated with phytohaemagglutinin exhibited only normal karyotypes. Clones of B‐cell produced by Epstein‐Barr virus had only normal karyotypes in the CMML patients. These findings indicate that CMML and JCML are clonal haemopathies that originate in a partially committed myeloid progenitor cell.

Quantitative EEG Analyses and Surgical Outcome After Corpus Callosotomy

Summary: Purpose: To clarify the relation between quantitative electroencephalogram (EEG) findings and outcome following corpus callosotomy (CC).

HTLV-I proviral DNA in umbilical cord blood of babies born to carrier mothers

Human T-lymphotropic virus type I (HTLV-I) in cord blood raises the possibility of intrauterine transmission as an alternative pathway to transmission via breast milk. However, none of 7 children with HTLV-I proviral DNA positive cord blood had seroconverted by 24-48 months. Contamination of cord blood by maternal blood was precluded on the basis of viral load and IgA concentration. Thus cord blood proviral DNA is not a hallmark of intrauterine infection. Moreover, none of the cord blood samples of 9 formula-fed children later confirmed to be infected was positive for HTLV-I, indicating that intrauterine infection is not a likely candidate as an alternative pathway.

Orbital Tumor in Acute Myeloid Leukemia Associated with Karyotype 46,XX,t(8;21)(q22;q22): A Case Report

Orbital tumor formation in acute myeloid leukemia (AML) is rare as an initial symptom. Furthermore, orbital granulocytic sarcoma (myeloid sarcoma) in pediatric patients is uncommon. We describe a 5-year-old Japanese girl with a left orbital mass as an initial symptom of AML, the mass revealed by computed tomography. Periperal blood and bone marrow pictures and a chromosomal analysis disclosing 46,XX,t(8;21)(q22;q22) showed AML (M2 according to the French-American-British classification). She was treated with antileukemic chemotherapy systemically. Three weeks after the initiation of chemotherapy, the orbital tumor regressed markedly. AML as an initial symptom of the orbital mass should be fully considered in a differential diagnosis, even in the absence of typical leukemic symptoms, and chromosomal analysis and immunophenotypical analysis may explain the pathogenesis of the extramedullary leukemic tumor.

Incidence and Causes of Intracranial Hemorrhage in Infancy: A Prospective Surveillance Study after Vitamin K Prophylaxis

In order to evaluate the effect of vitamin K prophylaxis on the incidence of intracranial hemorrhage (ICH) in infants aged from 1 week to 12 months, a prospective surveillance study, from 1974 to 1988, was performed on the well-defined population of Nagasaki Prefecture, Japan. The incidence of ICH in infancy markedly decreased, from 34.3/100,000 to 10.1/100,000 live births, with the oral administration of vitamin K2 at both birth and 1 week, or with additional supplementation at 1 month of age. The diminished incidence was attributed to the decreased occurrence of acute ICH due to late hemorrhagic disease (LHD), a late onset form of vitamin K deficiency, and chronic subdural hematoma. On comparing the possible etiological factors, and clinical and laboratory findings between these 2 groups, it became apparent that chronic subdural hematoma shared some etiological factors (such as breast-feeding, liver dysfunction and no supplementation of vitamin K) with LHD. Furthermore, chronic subdural hematoma developed in some patients who had previously had acute ICH due to LHD. These findings suggest that coagulopathy due to vitamin K deficiency, including LHD, is causally related in the majority of, if not all, cases of chronic subdural hematoma without any history of trauma or central nervous system infections.