Urine Desmosine as a Novel Biomarker for Bronchopulmonary Dysplasia and Postprematurity Respiratory Disease in Extremely Preterm or Low Birth Weight Infants.

OBJECTIVE: This study aimed to evaluate whether elevated urine desmosine levels at 3 weeks of age were associated with severe radiological findings, bronchopulmonary dysplasia (BPD), and post-prematurity respiratory disease (PRD) in extremely preterm (EP) or extremely low birth weight (ELBW) infants. STUDY DESIGN: This study recruited 37 EP (22-27 completed weeks) or ELBW (<1,000 g) infants. Urine was collected between 21 and 28 postnatal days, and desmosine was measured using an enzyme-linked immunosorbent assay kit; the urine creatinine level was also measured. Bubbly/cystic lungs were characterized by emphysematous chest X-rays on postnatal day 28. Furthermore, provision of supplemental oxygen or positive-pressure respiratory support at 40 weeks' postmenstrual age defined BPD, and increased medical utilization at 18 months of corrected age defined PRD. The desmosine/creatinine threshold was determined by receiver operating characteristic analysis. The adjusted risk and 95% confidence interval (CI) for elevated urine desmosine/creatinine levels were estimated by logistic regression analysis. RESULTS: Elevated urine desmosine/creatinine levels higher than the threshold were significantly associated with bubbly/cystic lungs (8/13 [61.5%] vs. 2/24 [8.3%], p = 0.001), BPD (10/13 [76.9%] vs. 8/24 [33.3%], p = 0.02), and PRD (6/13 [46.2%] vs. 2/24 [8.3%], p = 0.01). After adjusting for gestational age, birth weight, and sex, the urine desmosine/creatinine levels were significantly higher in those who were highly at risk of bubbly/cystic lungs (odds ratio [OR], 13.2; 95% CI, 1.67-105) and PRD (OR, 13.8; 95% CI, 1.31-144). CONCLUSION: Elevated urine desmosine/creatinine levels on the third postnatal week were associated with bubbly/cystic lungs on day 28 and PRD at 18 months of corrected age in EP or ELBW infants. KEY POINTS: · Urine desmosine was prospectively measured in 3-week-old EP/ELBW infants.. · Elevated urine desmosine levels were associated with emphysematous radiological findings on day 28, PRD at 18 months of corrected age.. · Urine desmosine may be a promising biomarker indicating lung damage in EP/ELBW infants..

Intrauterine Ureaplasma is associated with small airway obstruction in extremely preterm infants.

BACKGROUND: The long-term follow-up of lung function (LF) in extremely preterm (EP) infants with bronchopulmonary dysplasia (BPD) has shown a worldwide increase in small airway obstructions (SAO). OBJECTIVES: We investigated the relationships between intrauterine Ureplasma infection in EP infants and bubbly/cystic lung, BPD, and SAO at school age. METHODS: Placental pathology, placental Ureaplasma DNA (pU-DNA), and cord blood immunoglobulin M (IgM) (C-IgM) were investigated in 360 EP infants born from 1981 to 2004. Maternal amniotic inflammatory response (M-AIR) scores and hemosiderin deposition (HD) were estimated in the chorioamnion. The study subjects were divided into groups based on their M-AIR scores. Their LF at school age was compared with those of 33 healthy siblings. FINDINGS: pU-DNA and C-IgM were significantly related to SAO at school age (p < 0.012). M-AIR score 3 and pU-DNA >1000 units had an odds ratio (OR) of 35 (95% confidence interval: 10-172) and 18 (5.6-67) for bubbly/cystic lung, and 11 (3.1 - 43) and 31 (4.5-349) for severe BPD, and 5.3 (2.1-11) and 12 (2.4-74) for SAO, respectively. The ORs of surfactant treatment, BPD grade III, O2 at 40 weeks, HD, and C-IgM >30 mg/dl for SAO were 0.21 (0.075-0.58), 5.3 (2.1-15), 2.5 (1.4-4.6), 3.6 (1.5-9.1) and 2.5 (1.0-5.2). 84% (90/107) SAO infants showed no or mild BPD in infancy, and 61% of infants had no severe CAM. CONCLUSION: Our long-term cohort study of LF in EP infants revealed that intrauterine Ureaplasma was associated with bubbly/cystic lung, severe BPD, and SAO at school age.

Longitudinal impairment of lung function in school-age children with extremely low birth weights.

OBJECTIVES: To assess lung function and long-term respiratory outcomes in extremely low birth weight (ELBW) survivors. WORKING HYPOTHESIS: ELBW, especially with respiratory complications in the neonatal period, affects lung function at a later age. STUDY DESIGN: Longitudinal retrospective study. PATIENT-SUBJECT SELECTION: Lung function was evaluated in 89 ELBW survivors (at ages 8 and 12) with or without a history of bronchopulmonary dysplasia (BPD) or a bubbly/cystic lung appearance in the neonatal period. METHODOLOGY: FVC, FEV1 , FEF50 , and FEF75 were measured using spirometry. Two-way repeated-measures ANOVA was used to compare lung function and deterioration time course from 8 to 12 years of age. RESULTS: Lung function variables were significantly and positively correlated between 8 and 12 years: %FVC (R2 = 0.558), %FEV1 (R2 = 0.539), %FEF50 (R2 = 0.412), and %FEF75 (R2 = 0.429). Lung function values were lower than Japanese reference values, especially in children with a history of severe BPD or a bubbly/cystic appearance. %FEV1 and FEV1 /FVC ratio worsened from 8 to 12 years of age: 83.0 ± 17.0% versus 76.6 ± 17.8% (mean difference, 95%CI: -6.43, -9.10 to -3.75) and 84.0 ± 10.1% versus 78.2 ± 13.4% (mean difference, 95%CI: -5.82, -8.56 to -3.08), regardless of whether or not there was a history of neonatal respiratory disease. CONCLUSIONS: In ELBW survivors, the obstructive pattern of lung function impairment deteriorated from 8 to 12 years of age, independent of the presence of severe BPD or bubbly/cystic appearance in the neonatal period.

Risk factors associated with a decreased estimated glomerular filtration rate based on cystatin C levels in school-age children with extremely low birthweight.

AIM: A single centre retrospective cohort study was designed to investigate the estimated glomerular filtration rate (eGFR) in school-age children born with extremely low birthweight (ELBW) and to determine risk factors predictive of decreased eGFR. METHODS: We compared eGFR based on cystatin C (CysC-eGFR) between school-age children born with ELBW (ELBW group, n = 48; median gestational age: 26.9 weeks; median birthweight: 792 g) and children born at term (control group, n = 48). The ELBW group was then further divided into a decreased CysC-eGFR subgroup (eGFR <90 mL/min per 1.73 m2 , n = 20) and a normal CysC-eGFR subgroup (n = 28), and perinatal background factors were compared. RESULTS: The ELBW group showed a significantly lower CysC-eGFR compared with the control group (P < 0.001). Comparison between the decreased and normal CysC-eGFR subgroups in the ELBW group showed that children with lower birthweight, shorter gestational age, lower 5-min Apgar score, longer length of mechanical ventilation, lower weight gain in the first 11 weeks, chronic lung disease, and postnatal corticosteroid administration had significantly decreased CysC-eGFR. Multivariate logistic regression showed that a lower 5-min Apgar score was the only independent risk factor for decreased CysC-eGFR. CONCLUSIONS: CysC-eGFR might already be decreased at school age in children born with ELBW. Renal assessment in regular follow-up examinations is recommended.

Safety of Bifidobacterium breve (BBG-01) in preterm infants.

BACKGROUND: Since 1982, viable cells of Bifidobacterium breve (BBG-01) have been used in pediatric patients for clinical conditions such as intractable infantile diarrhea, preterm status, and pediatric surgery. Although the efficacy of BBG-01 has been widely reported, adverse events related to the use of BBG-01 have been reported in very few cases. METHODS: In order to trace adverse events seen by 109 doctors in 88 medical institutions where BBG-01 was used, a questionnaire survey of the number of occurrences and details of each case was conducted. RESULTS: Eighty-six clinicians (70 institutions) responded to the questionnaire (response rate, 78.9%). Number of respondents according to department of diagnosis (no. BBG-01-treated infants) was as follows: pediatrics, 29 respondents (10 938 patients); premature and newborn medicine, 26 (10 677 patients); obstetrics and gynecology, 1 (1212 patients) and pediatric surgery, 22 (169 patients). More than 90% of the total BBG-01-treated patients (23 092 patients) were in the departments of premature and newborn medicine and pediatrics, and BBG-01 had been used mainly in preterm infants and children with intractable diarrhea. Adverse events occurred in two extremely premature infants with functional ileus due to starch aggregates as vehicle, and in two surgical neonates with bacteremia caused by B. breve genetically identical to BBG-01, and no serious adverse events with poor outcome were reported. CONCLUSION: Adverse events related to the use of BBG-01 have an extremely low incidence and are mild in severity, thus ensuring the superior safety of this preparation.

SAMD9 mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7.

Adrenal hypoplasia is a rare, life-threatening congenital disorder. Here we define a new form of syndromic adrenal hypoplasia, which we propose to term MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) syndrome. By exome sequencing and follow-up studies, we identified 11 patients with adrenal hypoplasia and common extra-adrenal features harboring mutations in SAMD9. Expression of the wild-type SAMD9 protein, a facilitator of endosome fusion, caused mild growth restriction in cultured cells, whereas expression of mutants caused profound growth inhibition. Patient-derived fibroblasts had restricted growth, decreased plasma membrane EGFR expression, increased size of early endosomes, and intracellular accumulation of giant vesicles carrying a late endosome marker. Of interest, two patients developed myelodysplasitc syndrome (MDS) that was accompanied by loss of the chromosome 7 carrying the SAMD9 mutation. Considering the potent growth-restricting activity of the SAMD9 mutants, the loss of chromosome 7 presumably occurred as an adaptation to the growth-restricting condition.

Major neonatal surgery: psychosocial consequence of the patient and mothers.

PURPOSE: Our previous studies of long-term QOL after major neonatal surgery revealed an unexpectedly high incidence of mental retardation as well as emotional and psychosocial problems, and the patients' QOL correlated with maternal QOL and post-traumatic stress disorder (PTSD). The main purpose of this study was to clarify the risk factors affecting long-standing maternal PTSD. MATERIALS AND METHODS: Sixty-eight patients, aged between 6 and 17years, and their mothers were enrolled in this study. The underlying diseases included congenital diaphragmatic hernia in 21, anorectal anomalies in 25 and esophageal atresia in 22. Psychoanalysts carried out intelligence tests, the Child Behavior Checklist and QOL evaluation in the patients. QOL was evaluated with WHOQOL26 and PTSD with IES-R questionnaires in their mothers. The mothers were divided into two groups; low- and high-risk groups according to PTSD score. RESULTS: Patient QOL scores correlated positively with maternal QOL (p<0.05) and negatively with maternal PTSD scores (p<0.05). There were significant differences in total number of hospital admissions (p<0.05), feeling of economic burden (p<0.05), and satisfaction with husband's help (p<0.01) between the two groups. CONCLUSION: Risk factors for maternal PTSD include repeated hospitalization, a feeling of economic burden, and lack of satisfaction with husband's help.

Perinatal factors associated with long-term respiratory sequelae in extremely low birthweight infants.

OBJECTIVE: To assess lung function at 8 years old in extremely low birthweight (ELBW) survivors and to identify perinatal determinants associated with impaired lung function. DESIGN: Retrospective cohort study. SETTING: Level III neonatal intensive care unit. PATIENTS: ELBW survivors born in 1990-2004 with available spirometry at 8 years old were studied. Children were excluded if they had a Wechsler Intelligence Scale for Children Third Edition full IQ <70. MAIN OUTCOME MEASURES: Multivariate logistic regression analysis was used to identify perinatal determinants associated with airway obstruction (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <80%) at school age and the predictive power of potential determinants. Potential risk factors and predictors assessed in this study were gestational age, birth weight, small for gestational age, sex, chorioamnionitis, premature rupture of membranes, antenatal steroids, surfactant administration, respiratory distress syndrome, postnatal steroids, severe bronchopulmonary dysplasia and bubbly/cystic appearances of the lungs by X-ray during the neonatal period. RESULTS: Of 656 ELBW survivors, 301 (45.9%) had attended a school-age follow-up at 8 years old. A total of 201 eligible children completed the lung function test. Bubbly/cystic appearance of the lungs (OR 4.84, 95% CI 1.26 to 18.70) was associated with a low FEV1/FVC ratio. Children with bubbly/cystic appearance had characteristics of immaturity and intrauterine inflammation. CONCLUSIONS: Within a cohort of ELBW infants, a bubbly/cystic appearance of the lungs in the neonatal period was the strongest determinant of a low FEV1/FVC ratio at school age.

Psychosocial and cognitive consequences of major neonatal surgery.

PURPOSE: To evaluate the long-term quality of life (QOL) of patients who had undergone major neonatal surgery, the psychosocial and cognitive consequences of neonatal surgical stress were assessed when the patients reached school age. MATERIALS AND METHODS: Seventy-two patients who had undergone major neonatal surgery were enrolled in this study. Their primary diseases were anorectal malformation (ARM) in 27 cases, esophageal atresia (EA) in 23, and congenital diaphragmatic hernia (CDH) in 22. Intelligence tests using Wechsler Intelligence Scale for Children III (WISC-III) or a developmental test and the Child Behavior Checklist were conducted through questionnaires and interviews with clinical psychologists. RESULTS: Mental retardation (MR) was apparent in 25% of EA, 20% of ARM, and 18% of CDH, significantly higher than the 2% to 3% commonly found in the general population. The clinical range (CR) of the Child Behavior Checklist was seen in 35% of EA, 59% of ARM, and 38% of CDH, which is also significantly higher than the 25% typically seen in the general population. No significant differences in MR and CR were seen among the primary diseases. The most important factors influencing MR and CR remain to be identified. CONCLUSIONS: To ensure true quality of life after neonatal surgical stress, pediatric surgeons must consider not only physical assessments but also cognitive, emotional, and psychosocial assessments.

Meconium-related ileus in extremely low-birthweight neonates: etiological considerations from histology and radiology.

BACKGROUND: A nationwide survey on neonatal surgery conducted by the Japanese Society of Pediatric Surgeons has demonstrated that the mortality of neonatal intestinal perforation has risen over the past 15 years. The incidence of intestinal perforation in extremely low-birthweight (ELBW) neonates has been increasing as more ELBW neonates survive and as the live-birth rate of ELBW has increased. In contrast to necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP), the pathogenesis of meconium-related ileus, defined as functional bowel obstruction characterized by delayed meconium excretion and microcolon, remains unclarified. METHODS: The histology of 13 ELBW neonates with intestinal perforation secondary to meconium-related ileus was reviewed, and the radiology of 33 cases of meconium-related ileus diagnosed on contrast enema was reviewed. Specimens obtained from 16 ELBW neonates without gastrointestinal disease served as age-matched controls for histological assessment. RESULTS: The size of the ganglion cell nucleus in meconium-related ileus and in control subjects was 47.3 ± 22.0 µm(2) and 37.8 ± 11.6 µm(2), respectively, which was not significantly different. In all cases of meconium-related ileus, contrast enema demonstrated a microcolon or small-sized colon, with a gradual caliber change in the ileum and filling defects due to meconium in the ileum or colon, showing not-identical locations of caliber changes and filling defects. CONCLUSION: Morphological immaturity of ganglia was not suggested to be the pathogenesis of meconium-related ileus. Impaction of inspissated meconium is not the cause of obstruction, but the result of excessive water absorption in the hypoperistaltic bowel before birth, although the underlying mechanism responsible for the fetal hypoperistalsis remains unclear.

Biphasic Aire expression in early embryos and in medullary thymic epithelial cells before end-stage terminal differentiation.

The roles of autoimmune regulator (Aire)-expressing medullary thymic epithelial cells (mTECs) in the organization of the thymic microenvironment for establishing self-tolerance are enigmatic. We sought to monitor the production and maintenance of Aire-expressing mTECs by a fate-mapping strategy in which bacterial artificial chromosome transgenic (Tg) mice expressing Cre recombinase under the control of the Aire regulatory element were crossed with a GFP reporter strain. We found that, in addition to its well recognized expression within mature mTECs, Aire was expressed in the early embryo before emergence of the three germ cell layers. This observation may help to explain the development of ectodermal dystrophy often seen in patients with AIRE deficiency. With the use of one Tg line in which Cre recombinase expression was confined to mTECs, we found that Aire(+)CD80(high) mTECs further progressed to an Aire(-)CD80(intermediate) stage, suggesting that Aire expression is not constitutive from after its induction until cell death but instead is down-regulated at the beginning of terminal differentiation. We also demonstrated that many mTECs of Aire-expressing lineage are in close contact with thymic dendritic cells. This close proximity may contribute to transfer of tissue-restricted self-antigens expressed by mTECs to professional antigen-presenting cells.

Focal intestinal perforation in extremely-low-birth-weight neonates: etiological consideration from histological findings.

In Japan, mortality due to intestinal perforation has been increasing for the last 15 years, as the survival rate of extremely-low-birth-weight neonates (ELBWs) has been increasing. In our NICU, although the incidence of necrotizing enterocolitis has been decreasing, that of focal intestinal perforation (FIP) has been increasing. To elucidate the pathogenesis of FIP, a histological study was performed. For the last 20 years, in our NICU, 11 ELBWs with FIP, including one with multiple perforations and impending rupture, underwent laparotomy and enterostomy. The intestinal wall around the perforation was resected for histological study. Histological studies revealed well-developed ganglion cells in all the cases. Although some lymphocytic infiltration and hemorrhage were observed, no apparent neutrophilic infiltration, or necrotic change was identified in any case. No evidence of microcirculatory impairment was identified. The intestinal musculature discontinued abruptly with thinning in three cases, and without thinning in the others. The histology of impending rupture showed an absence of the muscularis with preservation of the remaining components of the bowel wall. The findings that the punched-out perforations had the appearance of Hirschsprung's disease, FIP exclusively occurred in ELBWs, and that neither mechanical obstruction nor necrotic change could be identified as the cause of the perforation suggest that immature bowel movement and congenital muscle defects may be involved in the pathogenesis of FIP.

Neonatal myocardial infarction due to thrombotic occlusion.

Neonatal myocardial infarction is rare and its prognosis is poor. We describe the clinical course and autopsy findings of a newborn female with myocardial infarction. Her clinical course was rapidly progressive, becoming fatal before we could detect the cause. Autopsy demonstrated significant occlusion of the left coronary artery as well as evidence of new infarction, suggesting that the event occurred at birth. This case illustrates myocardial infarction as a possible cause of early neonatal death.

Identification of the motilin cells in duodenal epithelium of premature infants.

BACKGROUND: The aim of the present study was to examine the presence of motilin in the duodenal epithelial cells of premature infants of < 32 weeks gestation. METHODS: Specimens from 10 deceased infants (gestational age: 26.4 +/- 2.7 weeks and birthweight: 808 +/- 303 g) were examined as subjects. All infants died of severe cardiopulmonary disorder or intraventricular hemorrhage (grade IV). The average survival period was 3.1 +/- 1.9 days. Autopsies were performed and formalin-fixed duodenums were immunostained with rabbit antiserum to motilin by the labeled streptavidin-biotin (LSAB) method. An adult duodenum obtained by pancreatoduodenectomy was also examined for the presence of motilin as a positive control specimen. An absorption test using motilin peptide was performed to prove the specificity of the binding with rabbit antiserum to motilin. RESULTS: Motilin-containing cells were detected in the adult specimen, and the binding by rabbit antiserum to motilin was completely inhibited by excess amounts of motilin peptide, indicating that this binding was specific to motilin. All 10 infants had presence of motilin antigen in the epithelial cells of their duodenums. CONCLUSION: This preliminary study indicates that the immunohistological analysis is specific to detect motilin-containing cells, and certifies the presence of motilin in duodenal epithelial cells of premature infants of < 32 weeks gestation, including one at only 22 weeks gestation.

[VNCOP-B (etoposide, mitoxantrone, cyclophosphamide, vincristine, predonisolone, bleomycin) therapy in elderly patients with aggressive non-Hodgkin lymphoma--a study of efficacy and safety, final report].

We experienced the VNCOP-B (etoposide, mitoxantrone, cyclophosphamide, vincristine, predonisolone, bleomycin) combination regimen for the treatment of elderly patients with aggressive non-Hodgkin lymphoma (NHL) in a multicenter study by 6 collaborative institutions. Patients were previously untreated > or = 60 years of age and received prophylactic G-CSF. Twenty patients entered this trial, and all of them were evaluated for feasibility, toxicity, and efficacy. The complete remission rate was 75.0%, with a 100% overall response rate; overall survival (OS) rate at 3 years was 79.1% (median follow up 761.5 days), with a 60.7% progression-free 3-year survival (PFS) rate (median follow-up 600.0 days). Our trial was promising and well-tolerated. According to IPI, high/high-intermediate risk was associated with significantly worse OS and PFS than low/low-intermediate risk (2-year OS: 51.8% versus 100.0%, p=0.0118; 2-year PFS: 33.3% versus 80.0%, p=0.0125). Grade 3/4 infections occurred in 3 patients, but no patients experienced it with predonisolone reduced.

Surgical management of congenital cardiac defects in neonates and young infants born with extremely low weight.

Surgical treatment of cardiac defects in infants born with extremely low weight is sometimes required during the neonatal period. Optimal timing of these operations has yet to be clarified. With this in mind, we reviewed our experience of surgical treatment for 29 infants born with extremely low weight between 1994 and 2001. The main surgical procedures were ligation of a patent arterial duct in 26, a Brock procedure in 2, and ligation of an aorto-pulmonary window in 1 infant. The age at operation ranged from 5 to 57 days, with a median of 30 days, and weighed from 506 to 902 g, with a median of 710 g. There were no deaths. For the 2 infants undergoing the Brock procedure, the reduced systemic blood flow also necessitated closure of the arterial duct. For almost all the 26 infants with a patent arterial duct, indomethacin was given as the initial therapy, but the duct had not closed completely. Increased symptomatology just before the operation due to reduced systemic blood flow, such as decreased cerebral blood flow, decreased urine output, and intestinal ischemia, mandated the earlier surgical ligation (r = -0.576, p = 0.004). The youngest infant needed an infusion of catecholamines perioperatively to maintain stable hemodynamic conditions (r = 0.554, p = 0.003). In 4 infants, including the youngest 2, steroids were administered intravenously just after the ligation. Our results suggest that reduced systemic blood flow is the main indication of surgical repair in infants born with extremely low weight. Even for one in whom the supply of pulmonary blood is dependent on the arterial duct, early reconstruction of the pulmonary arterial pathways, using the Brock procedure, followed by ligation of the duct, is required. Acute adrenal insufficiency should not be overlooked just after the surgery, particularly in the youngest patients.

Hepatoblastoma in children of extremely low birth weight: a report from a single perinatal center.

BACKGROUND/PURPOSE: The incidence of hepatoblastoma (HB) in children of low birth weight is increasing. In the authors' institute, 5 infants of extremely low birth weight (ELBW) were found to have HB. The purpose of this study was to identify the characteristics of these infants to elucidate the pathogenesis of HB arising in ELBW infants. METHODS: Birth weight (BW) ranged from 554 to 750 g (mean, 654 g) and gestational age from 23 to 29 weeks (mean, 25.8 weeks). Medical records of the 5 patients were reviewed, and perinatal treatments were compared with those of ELBW infants without HB. RESULTS: One patient with intraabdominal hemorrhage had emergency operation, which was followed by early postoperative death. The parents of one child refused treatment because of associated severe anomalies. He died of the growing tumor 4 months after diagnosis. The remaining 3 patients had radical operation performed after intraarterial chemoembolization and systemic chemotherapy. One died of hepatic failure 7 months after operation. Two are alive 5 and 9 months after operation. The incidence of HB among ELBW infants was estimated to be about 0.5% in our institute. The mean durations of mechanical ventilation, oxygen inhalation, and hospitalization during the neonatal periods in cases of HB were significantly longer than those in BW matched control infants (P <.01). CONCLUSIONS: ELBW children have a high risk for HB. In follow-up of ELBW infants, serum alpha-fetoprotein or abdominal ultrasonography may be useful to detect early HB. The children with HB received perinatal treatments for a significantly longer time, which suggests that perinatal intensive and long-term medical treatments may be involved in the tumorigenesis in the highly sensitive immature liver.

Dendritic cells are decreased in blood and accumulated in granuloma in tuberculosis.

Immunity against tuberculosis consists of innate and adaptive immune responses. In this study, we investigated the dynamics of dendritic cells (DC), which are known to elicit a variety of immune responses, in patients with tuberculosis. CD11c(+) peripheral blood DC were decreased in patients with tuberculosis. Immunohistochemical analyses demonstrated that a number of fascin(+), CD11c(+), HLA-DR(+) DC were infiltrating the lymphocyte areas of the tuberculous granulomas (tubercles). Immunohistochemical analyses also demonstrated that interferon-gamma-producing Th1 cells were increased in the tubercles of the patients, indicating the presence of Th1 polarization at least in the context of inflammatory tissues. In vitro coculture of autologous naive T cells with CD11c(+) or CD11c(-) DC pretreated with Bacillus Calmette Guérin augmented the production of Th1 cells. These findings suggested that the trafficking of DC from the peripheral blood into the tubercles causes a dominant Th1 balance and thus plays an essential role in the immunity against tuberculosis.