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We report the case of the third patient with Tsukahara-Azuno-Kaiji syndrome. It is characterized by brachydactyly A1, dwarfism, microcephaly, scoliosis, intellectual disability, ptosis, and hearing loss. The first patient was reported in 1989, and the second in 2010. The present patient had many features in common with the previous 2 patients, with a few minor differences. Although this combination of symptoms is very characteristic, the clinicians should know about this syndrome to diagnose it. The syndrome in this patient appeared sporadically, and chromosome G-banding revealed a normal female karyotype of 46XX. However, further genetic research could not be performed. Steady accumulation of information will enable us to discover the true clinical and genetic nature of the disease and to make the diagnosis more easily.

Objective Deep brain stimulation (DBS) of the bilateral subthalamic nucleus (STN) is a standard surgical treatment option in patients with advanced Parkinson's disease. Adverse effects on cognitive function have been reported, impacting the quality of life of patients and caregivers. We aimed to investigate a quantitative predictive preexisting cognitive factor for predicting postoperative cognitive changes. Methods Thirty-five patients underwent STN-DBS. A battery of neuropsychological tests were used to examine executive function, processing speed, and visuospatial function both preoperatively and 1 year postoperatively. A multiple logistic regression analysis was performed to investigate the relationships between preoperative factors and cognitive outcomes. The predictive value of the preoperative factors for global cognitive decline during long-term follow-up were evaluated. Results The patients exhibited significant changes in processing speed and visuospatial function after surgery. Using reliable change index values, lower preoperative scores on the Similarities and Object Assembly subtests of the Wechsler Adult Intelligence Scale III were associated with decreases in visuospatial function at 1 year after DBS. The odds ratios were 10.2 for Similarities and 9.53 for Object Assembly. The proportion of Mini Mental State Examination–maintained patients with low scores on the Similarities subtest was significantly lower than that of patients with high scores at 3 and 5 years. No factors were found to be related to decreases in processing speed. Conclusions Preoperative evaluation of the Similarities and Object Assembly subtests may be useful to identify patients who are at a greater risk of experiencing decreases in visuospatial functioning after STN-DBS. Furthermore, a low score on the Similarities subtest may predict future global cognitive deterioration.

Chronic intractable neuropathic pain after central or peripheral nervous system injury remains refractory to therapeutic intervention. Using microarray and RT-qPCR methods, we found that Noggin mRNA is downregulated in the lumbar enlargement 2 weeks after chronic constriction injury (CCI) in rats. Eight-week-old female Sprague Dawley rats were used for the CCI model. Two weeks after CCI, rats underwent a laminectomy at L5 under halothane anesthesia, and a silicone tube connected to an osmotic minipump was inserted intrathecally for 14 days. Rats were administered Noggin ranging from 10 ng/ml to 10 μg/ml. Phosphate buffered saline (PBS) was used as a control. The time course of mechanical allodynia was assessed for 5 weeks using von Frey filaments. An ANOVA showed that rats administered Noggin at 2 μg/ml had significantly less mechanical allodynia compared with controls. We next compared the effect of intrathecal administration (14 days) of Noggin (2 μg/ml), bone morphogenetic protein 4 (BMP4; 2 μg/ml), or BMP4 (μg/ml) + Noggin (μg/ml) with controls. Only Noggin administration significantly reduced mechanical allodynia in the CCI model. Fluorescence immunohistochemistry indicated that Noggin administration decreased astrocyte accumulation in the dorsal horn compared with PBS after administration for one week. BMP4-driven conversion of oligodendrocyte progenitor cells (OPCs) to type 2 astrocytes is inhibited by Noggin Hampton et al. (2007) . We speculated that Noggin administration inhibits the conversion of OPCs to astrocytes, and decreases glial fibrillar acidic protein expression. This histological condition could decrease neuropathic pain., Highlights • Noggin mRNA is significantly down-regulated two weeks after CCI in rats. • The mechanical allodynia was decreased in Noggin administration at seven days. • Noggin administration influenced GFAP expression and reduced mechanical allodynia.

This longitudinal study investigated the effects of various lifestyle-related factors - including sleep duration, shift work, and actual days taken off work - on new-onset metabolic syndrome (MetS).A total of 39,182 male employees (mean age 42.4 ± 9.8 years) of a local government organization in Japan were followed up for a maximum of seven years, between 1999 and 2006. Multivariate analysis (Cox proportional hazard method) identified seven high-risk lifestyle factors that were significantly associated with new-onset MetS or a range of metabolic factors (obesity, hypertension, hyperglycemia, dyslipidemia): (1) short sleep duration (5 h/day), (2) shift work, (3) insufficient number of days off work, (4) always eating until satiety, (5) not trying to take every opportunity to walk, (6) alcohol intake ≥60 g/day, and (7) smoking. In addition, a higher number of these high-risk lifestyle factors significantly promoted the onset of MetS. The hazard ratio for MetS associated with 0-1 high-risk lifestyle parameters per subject at the baseline was set at 1.00. Hazard ratios associated with the following numbers of high-risk lifestyle parameters were: 1.22 (95% CI 1.15-1.29) for 2-3 of these parameters; and 1.43 (1.33-1.54) for 4-7.An increase in the number of high-risk lifestyle factors - such as short sleep duration, shift work, and an insufficient number of days off work - increased the risk of MetS onset. Comprehensive strategies to improve a range of lifestyle factors for workers, such as sleep duration and days off work, could reduce the risk of MetS onset.

Management of chronic thromboembolic pulmonary hypertension (CTEPH) has recently improved because of advances in pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA), and disease-targeted medications. However, patients with inoperable CTEPH or persistent pulmonary hypertension (PH) after these interventions continue to exhibit impaired exercise capacity and limited quality of life (QOL).Eight patients with inoperable or residual CTEPH (mean age, 64±12 years; WHO functional class II/III, 6/2; mean pulmonary artery pressure, 47±13 mmHg) in stable condition and receiving disease-targeted medications participated in a 12-week home-based pulmonary rehabilitation program (muscle strength training, respiratory exercises, and walking) with supervised hospital sessions from March 2012 to January 2014. Efficacy parameters were prospectively evaluated at baseline and at completion of the 12-week program.After completion of the pulmonary rehabilitation program, the 6-minute walking distance (6MWD) (33.3±25.1 m), St. George׳s Respiratory Questionnaire activity score, quadriceps force, and 7-day physical activity level were significantly improved compared with baseline. All subjects completed the rehabilitation program. Although one patient experienced presyncope during the in-hospital exercise sessions, no other severe adverse events or complications of pulmonary rehabilitation were observed.These findings suggest that home-based pulmonary rehabilitation with closely supervised sessions may safely improve exercise capacity, leg muscle strength, general activity in daily life and health-related QOL in CTEPH patients.

Purpose The purpose of this study was to investigate computed tomography (CT) and clinical features relating to calcifications within the parotid gland of patients with Sjogren's syndrome (SS). Methods Data from 30 patients with SS who had been examined by CT were extracted from our radiological information database accumulated from 2001 to 2011, and their CT images were reread carefully. Of these patients, 14 (all female; age range 20–95years; mean age 61.4years) with calcifications within the parotid gland were retrospectively investigated with CT findings. The relationship between calcification occurrence and clinical symptoms including parotid swelling and/or saliva colic was investigated. The degree of destruction of the parotid gland on CT images was also evaluated. Results All calcifications of 14 patients were located within the parotid gland, not in the parotid duct. CT images of all calcifications showed small and regular round shapes. Multiple occurrences of calcifications were recognized in 10 patients, and a solitary occurrence was seen in 4 patients. Seven patients had bilateral calcifications. There was little relationship between the occurrence of calcifications and clinical symptoms, and the severity of destruction of the parotid gland. Conclusion The presented CT and clinical features would be peculiar to SS because too many patients lacked the typical features of sialoliths within the parotid gland.

Object Clinical use of autologous induced pluripotent stem cells (iPSCs) could circumvent immune rejection and bioethical issues associated with embryonic stem cells. Spinal cord injury (SCI) is a devastating trauma with long-lasting disability, and current therapeutic approaches are not satisfactory. In the present study, the authors used the neural stem sphere (NSS) method to differentiate iPSCs into astrocytes, which were evaluated after their transplantation into injured rat spinal cords. Methods Induced pluripotent stem cell–derived astrocytes were differentiated using the NSS method and injected 3 and 7 days after spinal contusion–based SCI. Control rats were injected with DMEM in the same manner. Locomotor recovery was assessed for 8 weeks, and sensory and locomotion tests were evaluated at 8 weeks. Immunohistological parameters were then assessed. Results Transplant recipients lived for 8 weeks without tumor formation. Transplanted cells stretched their processes along the longitudinal axis, but they did not merge with the processes of host GFAP-positive astrocytes. Locomotion was assessed in 3 ways, but none of the tests detected statistically significant improvements compared with DMEM-treated control rats after 8 weeks. Rather, iPSC transplantation caused even greater sensitivity to mechanical stimulus than DMEM treatment. Conclusions Astrocytes can be generated by serum treatment of NSS-generated cells derived from iPSCs. However, transplantation of such cells is poorly suited for repairing SCI.

Objective The objective of this longitudinal epidemiological study was to investigate the association of risk factors for cardiovascular illness with sleep duration and shift work. Methods This study used data obtained at medical checkups conducted in 1999 and 2006 for the employees of a local government organization in Japan (covering 21,693 male employees and 2109 female employees). The medical checkup data included (1) body measurements, (2) blood test parameters, and (3) replies to a self-administered questionnaire (inquiring about sleep duration, with or without shift work, etc.). On the basis of these data, we conducted multiple logistic regression analyses to study the association between the risk of new-onset obesity, hypertension, hyperglycemia, hypertriglyceridemia, and hypo-high density lipoprotein (HDL) cholesterolemia and shift work as well as sleep duration. Results Among the male subjects who were engaged in shift work, the relative risk of new-onset obesity for those with a sleep duration of less than 5 h was 1.30 (95% CI, 1.14–1.49) higher than for those with sleep duration of 5–7 h. Furthermore, analysis using both engagement in shift work and sleep duration as dependent variables showed that the relative risks of new-onset obesity for those with a sleep duration of less than 5 h were 1.20 (95% CI, 1.09–1.32) for men and 1.7 (95% CI, 1.11–2.87) for women. Conclusions Short sleep duration is associated with onset of obesity.

Summary OBJECTIVE The high-affinity growth hormone (GH)-binding protein corresponds to the extracellular domain of GH receptor. The direct role of sex steroids in pubertal bone growth may be an increased GH receptor-coupled GH action. We examine the GH-binding protein (GHBP) activity before and after the suppression of female sex steroids and the relation of GHBP to pubertal growth. PATIENTS We studied six girls with central idiopathic sexual precocity without any prior gonadal suppression therapy. DESIGN We measured GHBP activity before and 12, 24 and 48 weeks after the treatment with s.c. injection of a GnRH agonist (leuprolide acetate) every 4 weeks. MEASUREMENT GHBP activity was measured by immunoprecipitation using anti-GH receptor monoclonal antibody. RESULTS The treatment caused a decrease in the LH and FSH responses to GnRH test and plasma oestradiol, which resulted in decreased urinary GH excretion, plasma IGF-I levels, height velocity and bone age maturation. GHBP activity before the start of the treatment was normal (75 ± 27% relative to adult pooled serum, mean ± SD), and it was increased above adult level (122 ± 29% at 48 weeks, P < 0.01) by the suppression of the pituitary-gonadal axis. There were significant negative correlations between GHBP and oestradiol (r=-0.452, n = 24, P < 0.05) and between GHBP and urine GH excretion (r = −0.462, n = 24, P < 0.05). CONCLUSIONS The high-affinity GHBP is increased by the withdrawal of female sex steroid. The clinical significance of this finding may be interference with the binding of GH to its receptor resulting in a reduced IGF-I level and decreased height velocity. The mechanism warrants further study.

Background: Cardiocirculatory effects of hemodynamically significant patent ductus arteriosus (hsPDA) have not been systematically studied in extremely low-birth-weight (ELBW) infants with respiratory distress syndrome (RDS). The objective of the present study was to evaluate the effects of hsPDA on the left ventricular output (LVO) and organ blood flows in ELBW infants with RDS. Methods: Extremely low-birth-weight infants (birth-weight

The axon reflex induced by intracutaneous application of capsaicin to the forearm of human subjects and the back of anesthetized rats pretreated with intravenous injection of Evans blue was investigated using sequential subtraction thermography. In the human experiment, thermograms showed an immediate and general temperature decrease after capsaicin injection. Four min after application, several spotty areas with a temperature increase ('hot spots') appeared within and outside of the flare caused by capsaicin-induced axon reflex. A vascular murmur was observed on ultrasonic Doppler flowscopy at the hot spots. In the rat experiment, two hot spots appeared, one cranial to and one caudal to the site of injection, within different dermatomes. Hot spots appeared in rats with the pretreatment of intravenous hexamethonium and surgical removal of the bilateral lumbar paravertebral sympathetic trunks. Postmortem examination of the rats revealed that these hot spots coincided with perforating blood vessels. It was suggested that hot spots in the axon reflex identified by subtraction thermograms are induced by a passive dilatation of perforating vessels which supply blood to the flare.

The implications of Bovine serum albumin (BSA) in cow's milk proteins in the pathogenesis of insulin-dependent diabetes mellitus (IDDM) have been suggested, but is controversial even in Caucasians, and have been addressed in limited studies in other ethnic groups. We studied the prevalence of antibodies to BSA (BSAAb) in sera from Japanese children with IDDM, and compared it to those in children with other diseases including non insulin-dependent diabetes mellitus (NIDDM), autoimmune thyroid disease (AITD) and congenital hypothyroidism (cretinism) by using enzymelinked immunosorbent assay (ELISA). Significant levels of BSAAb were detected in sera from non-diabetic normal children, and higher levels in younger (1-3 years of age) than in older children (4-9 years of age). Only 2 of 20 (10%) recent-onset IDDM patients of age ≥ 4 years were assessed to have high titers of BSAAb compared to normal controls, and none of 8 sera from those of age

アポクリン癌の細胞学的特徴を明確にするため, アポクリン癌9例と対照としてアポクリン化生の目立つ良性症例15例の穿刺細胞標本を用い, 細胞集塊の形態や個々の細胞所見について検索を行い, 以下の結果を得た.1. アポクリン癌は好酸性穎粒状の広い細胞質を有する良性化生細胞に類似した細胞からなるものの, 良性例と比べて多少なりとも細胞の散在性や重積性を示す傾向にあった.2. アポクリン癌にみられる細胞集塊は, 細胞境界が不鮮明なことが多く, しばしば泡沫状の細胞質を伴っていた.3. アポクリン癌では通常, 核の腫大や大小不同が目立っており, また大型の核小体が高頻度に出現した.このような細胞像の特徴を判定に活かすことにより, 穿刺細胞診におけるアポクリン癌の診断がより的確になるものと思われる.

Besides stimulating angiogenesis or cell survival, basic fibroblast growth factor (bFGF) has the potential for protecting neurons in the injured spinal cord.To investigate the effects of a sustained-release system of bFGF from gelatin hydrogel (GH) in a rat spinal cord contusion model.Adult female Sprague-Dawley rats were subjected to a spinal cord contusion injury at the T10 vertebral level using an IH impactor (200 kdyn). One week after contusion, GH containing bFGF (20 µg) was injected into the lesion epicenter (bFGF - GH group). The GH-only group was designated as the control. Locomotor recovery was assessed over 9 weeks by Basso, Beattie, Bresnahan rating scale, along with inclined plane and Rota-rod testing. Sensory abnormalities in the hind paws of all the rats were evaluated at 5, 7, and 9 weeks.There were no significant differences in any of the motor assessments at any time point between the bFGF - GH group and the control GH group. The control GH group showed significantly more mechanical allodynia than did the group prior to injury. In contrast, the bFGF - GH group showed no statistically significant changes of mechanical withdrawal thresholds compared with pre-injury.Our findings suggest that bFGF-incorporated GH could have therapeutic potential for alleviating mechanical allodynia following spinal cord injury.

OBJECTIVES The aim of study was to determine the associations of work hours and actual availability of weekly rest days with the onset of lifestyle-related diseases such as obesity, hypertension, hypertriglyceridemia, low levels of high-density lipoprotein (HDL) cholesterol and hyperglycemia. METHODS For this longitudinal study, we used data from checkups conducted in 1999 and 2006 for 30,194 men who worked for a local public institution in Japan. We calculated the cumulative incidence rates of onset of obesity, hypertension, hyperglycemia, hypertriglyceridemia and low HDL cholesterol over this 7-year period and performed a χ2 test to determine the association between the above diseases and work conditions (work hours and actual availability of weekly rest days) at the time of the baseline survey. We then performed multiple logistic regression analysis of the diseases that showed significant associations. RESULTS The adjusted odds ratio for the onset of hypertriglyceridemia in subjects who worked ≥9 hours was high (1.11 [95% CI: 1.02-1.22], p=0.02) in comparison with those who worked

The direct role of sex steroids in pubertal bone growth may be an increased growth hormone (GH) receptor-coupled GH action. We previously reported that suppression of sex steroids by a gonadotropin-releasing hormone (GnRH) agonist (leuprolide acetate) increases the activity of serum growth hormone-binding protein (GHBP), identical to the extracellular domain of GH receptor, in central idiopathic precocious puberty (CIPP). Since insulin-like growth factor (IGF) -binding protein 3 (IGFBP-3) is a GH-dependent IGF binding protein, we measured IGFBP-3 and GHBP before and after treatment with the GnRH agonist in eight children with CIPP. IGFBP-3 and GHBP were measured by radioimmunoassay and immunoprecipitation.The treatment suppressed gonadal function. The initial IGFBP-3 level was high. After the treatment, IGFBP-3 remained at this level despite a reduction in GH secretion. There was a significant positive correlation between IGFBP-3 level and GHBP activity (r=0.63, p

Objective To assess the acute cardiovascular response to aquatic exercise in patients with osteoarthritis. Design Blood pressure (BP) and heart rate (HR) were measured in 13 female patients with osteoarthritis (63.3 +/- 8.4 yrs) during aquatic walking for 40 mins. A double product (DP) value was calculated by multiplying systolic BP by HR to evaluate the workload of the heart. Results BP and DP increased transiently with a decrease in HR after water immersion. Aquatic walking induced increases in BP, DP, and HR. Furthermore, BP and DP increased sharply with an increase in HR on leaving the water. The mean maximum increases in systolic BP and DP during each process were 23.5 +/- 18.2 mm Hg and 2931.1 +/- 2758.5 mm Hg/min when entering the water, 36.5 +/- 16.5 mm Hg and 4557.2 +/- 3435.1 mm Hg/min during aquatic walking, and 38.5 +/- 18.9 mm Hg and 5132.3 +/- 3228.8 mm Hg/min on leaving the water. Conclusions Water immersion, aquatic walking, and the process of leaving the water induced marked increases in BP in patients with osteoarthritis.

Study design Our original performance test for evaluating the severity of cervical myelopathy, the triangle step test (TST), was introduced along with an assessment of its validity. Objective The TST was designed to evaluate the lower extremity motor function objectively and quantitatively. This study aimed to assess the validity of the test by analyzing the relation to the other analytic methods. Summary of background data Several rating scales and performance tests have been proposed to evaluate the severity of cervical myelopathy. Simple walking test is useful; however, the test is limited for the patients who can walk safely. Methods Each subject sitting on a chair was instructed to step on marks at each apex of a triangular board and the number of steps in 10 seconds was counted for each foot. The subjects were 270 cervical myelopathy patients who had visited our hospital since 2002. As a control group, 60 healthy adults also underwent this test. All subjects were simultaneously evaluated by the Nurick score, the Japan Orthopedic Association score and the finger grip and release test. An assessment of the effect of surgery was analyzed for 94 patients who underwent surgical treatments. Results The mean of the lower count for each subject (TST score) in the control group was 25.4 +/- 3.7 steps, which was superior to 18.4 +/- 5.2 steps for myelopathy patients. TST score significantly correlated to the other analytic measures for cervical myelopathy. Regarding the effect of surgery, a performance of 16.7 +/- 4.5 steps before surgery improved to 21.2 +/- 4.9 steps at follow-up. Patients who could step more than 20 times before surgery, showed greater neurologic recovery. Conclusion TST score correlated with other analytic methods for cervical myelopathy. This test is very useful to quantitatively evaluate lower extremity function and its improvement following surgical intervention.

Spinal cord evoked potentials elicited by direct stimulation of the spinal cord were monitored in 21 patients during thoracic or thoraco-abdominal aortic aneurysm surgery. Flexible catherer-type electrodes were used for both stimulating and recording. The basic pattern of the spinal cord evoked potential consisted of an initial spike and a subsequent polyphasic component. The earliest and most frequent alterations after cross-clamping of the aorta were changes in the configuration or amplitude of the polyphasic component. In 13 patients who exhibited no change except minor alterations of the polyphasic component during the initial test clamping for 15 or 20 min, subsequent graft replacements were safely performed without reimplantation of intercostal vessels. In 2 patients who had sudden cardiac arrests, the evoked potential completely disappeared. The polyphasic component disappeared first, followed by the initial spike. Another patient developed acute loss of the potential after the aneurysm was incised, presumably due to distal aortic hypoperfusion. In this case, prolonged distal hypotension resulted in flaccid paraplegia. Intraoperative monitoring of the spinal cord evoked potential is a useful method for the early detection of spinal cord ischemia during surgery requiring aortic occlusion.

In light of reports that the administration of fasudil, a Rho-kinase inhibitor, improved rats locomotor abilities following spinal cord injury, we hypothesized that combining fasudil with another type of therapy, such as stem cell transplantation, might further improve the level of locomotor recovery. Bone marrow stromal cells (BMSCs) are readily available for stem cell therapy. In the present study, we examined whether fasudil combined with BMSC transplantation would produce synergistic effects on recovery. Adult female Sprague-Dawley rats were subjected to spinal cord contusion injury at the T10 vertebral level using an IH impactor (200 Kdyn). Immediately after contusion, they were administrated fasudil intrathecally for 4 weeks. GFP rat-derived BMSCs (2.5x10(6)) were injected into the lesion site 14 days after contusion. Locomotor recovery was assessed for 9 weeks with BBB scoring. Sensory tests were conducted at 8 weeks. Biotinylated dextran amine (BDA) was injected into the sensory-motor cortex at 9 weeks. In addition to an untreated control group, the study also included a fasudil-only group and a BMSC-only group in order to compare the effects of combined therapy vs. single-agent therapy. Animals were perfused transcardially 11 weeks after contusion, and histological examinations were performed. The combined therapy group showed statistically better locomotor recovery than the untreated control group at 8 and 9 weeks after contusion. Neither of the two single-agent treatments improved open field locomotor function. Sensory tests showed no statistically significant difference by treatment. Histological and immunohistochemical studies provided some supporting evidence for better locomotor recovery following combined therapy. The average area of the cystic cavity was significantly smaller in the fasudil+BMSC group than in the control group. The number of 5-HT nerve fibers was significantly higher in the fasudil+BMSC group than in the control group on the rostral side of the lesion site. BDA-labeled fibers on the caudal side of the lesion epicenter were observed only in the fasudil+BMSC group. On the other hand, only small numbers of GFP-labeled grafted cells remained 9 weeks after transplantation, and these were mainly localized at the site of injection. Double immunofluorescence studies showed no evidence of differentiation of grafted BMSCs into glial cells or neurons. The Rho-kinase inhibitor fasudil combined with BMSC transplantation resulted in better locomotor recovery than occurred in the untreated control group. However, the data failed to demonstrate significant synergism from combined therapy compared with the levels of recovery following single-agent treatment.

Background Giant cell tumors of bone (GCTs), among the most common primary bone tumors, are characterized by the formation of abundant osteoclast-like multinucleated giant cells (MNCs). It is not yet clear about the origin of GCTs and which cells in the lesion are the true neoplastic component. Several recent reports suggested that MNCs are osteoclasts induced by stroma-like tumor cells expressing the ligand for receptor activator of NF-kB (RANKL), which is a membrane-bound osteoclast differentiation factor. This hypothesis suggests an osteoblast lineage origin of GCTs, although it has long been speculated about GCTs being of mesenchymal stem cell (MSC) origin. Methods We investigated the expression of osteoblastic differentiation markers in 10 human GCTs by reverse transcription-polymerase chain reaction and immunohistochemistry. We also performed osteoblastic and adipogenic differentiation assays using cultured cells derived from surgically resected lesions to estimate the stem cell-like properties. Results GCTs and derived stromal cells expressed many osteoblast lineage marker genes, such as collagen type I, bone sialoprotein, core binding factor a-1, and osteocalcin. Instead of stable expression of mRNA, osteocalcin was not detected among the proteins. The tumor-derived cultures showed osteoblastic but not adipogenic differentiation capability. These findings strongly suggest that GCTs are of osteoblast lineage origin. Conclusions Our results indicated that GCTs expressed many osteoblastic markers and showed properties of preosteoblast-like cells rather than those of MSCs. These observations may provide some insight into the mechanisms of disease progression and the origin of GCTs.

To learn the mechanism of low plasma insulin-like growth factor-I (IGF-I) despite high growth hormone (GH) secretion in patients with anorexia nervosa, we assessed human serum GH-binding protein (BP) (GH-BP), which has been shown to be identical to the extracellular domain of GH receptor, and therefore might reflect peripheral GH receptor expression (i.e. there is a significant linear correlation between GH-BP and IGF-I at less than 2.0 U/ml in healthy children). The serum GH-BP level was determined by gel filtration and confirmed by immunoassay using GH receptor monoclonal antibody. Furthermore, we analyzed serum IGF-binding proteins (IGFBPs) by the affinity cross-linking method to determine the GH-IGF-I axis in this condition. Measurement of GH-BP by the two assays gave identical results, suggesting that serum GH-BP corresponds to the extracellular domain of GH receptor. The low GH-BP and high IGFBP levels in patients with anorexia nervosa shown in this study, which were normalized by an improved nutritional state, would indicate resistance to GH as well as to IGFs in this condition, in which the former is in part compensated by high GH levels while the latter is not.

Avulsion of the lumbosacral nerve roots is rare. Since 1960, when, we believe, a case was reported for the first time, only thirty-five of these avulsions have been reported2,3,5,6, to our knowledge. In most patients, unilateral avulsion of the lumbosacral nerve roots is associated with a fracture of the pelvis and the lower limb. The diagnosis of a nerve-root avulsion is difficult to confirm. Radiographic evidence of a pseudomeningocele is the most reliable sign of such an avulsion, but a pseudomeningocele is not always present6. The role of magnetic resonance imaging and computed tomography myelograms in the diagnosis of nerve-root avulsions is unclear. We report the case of a patient who had a partial avulsion of the cauda equina associated with a lumbosacral fracture-dislocation that was diagnosed with magnetic resonance imaging and computed tomography myelograms. A nineteen-year-old man was first seen at the Funabashi-Municipal Medical Center in Chiba, Japan, after he had sustained a lumbosacral fracture-dislocation and fractures of the left second, third, and fourth lumbar transverse processes in a motor-vehicle accident (Figs. 1-A and 1-B). He was transported by ambulance and arrived at the hospital about thirty minutes after the accident. The initial neurological examination revealed flaccid paralysis and a complete sensory deficit from the second lumbar level (including the second lumbar nerve) caudally and the absence of reflexes in the knee and ankle of both lower limbs. He had no control of bladder and bowel function, and he had loss of sphincter tone. A computed tomography scan demonstrated a horizontal fracture at the base of the inferior articular process of the fifth lumbar lamina with a unilateral jumped-and-locked facet joint on the left between the fifth lumbar and first sacral vertebrae, with a resultant rotatory instability due to …

Using a new endotoxin-specific chromogneic limulus assay (Endoscopy test), endotoxin concentrations were measured in 93 specimens of cerebrospinal fluid (CSF) from 66 pediatric patients. Eighteen patients were diagnosed as having menigitios. Of these, 6 cases (group A) with gram-negative meningitis proven by culture had high CSF endotoxin concentrations of 115.3, (82-133) (median, range) pg/ml. Ten cases (group B) with gram-positive or aseptic meningitis had endotoxin concentrations of 2.15 (0.1-3.6) pg ml. Other 2 cases with bacterial meningitis (group C), in whom no pathogen was detected, had CSF endotoxin concentrations of more than 100 pg/ml. Four cases with encephalitis (group D) and 45 cases with non-meningitis or non- encephalitis (group E), had CSF endotoxin concentrations of less than 5 pg/ml. Despite a negative culture after antibiotic treatment in group A patients, endotoxin was cleared slowly from the CSF. A clearing of endotoxin from CSF was followed by alleviation of fever with a more gradual decline in CRP values. In 2 cases of group C, the negative bacterial culture appeared to be attributable to the previous treatment with antibiotics. However, these patients had high CSF endotoxin levels, indicating gram negative bacterial meningitis. In 17 CSF specimens from 5 patients of group A, in whom Haemophilus influenzae was detected on admission, an additional a latex agglutination test for the detection of H. influenzae polysaccharide antigen was performed. Only 3 specimens from 3 patients with CSF endotoxin concentrations of more than 80 pg/ml had a positive agglutination test. These results suggest that quantitation of endotoxin concentrations is useful for the diagnosis of gram-negative meningitis. And also, the clearance of endotoxin from CSF during treatment appears to be useful in determining the timing of when antibiotic should be stopped.

Inadequate blood sugar control in children with insulin-dependent diabetes mellitus (IDDM) sometimes results in low insulin-like growth factor-I (IGF-I) and sluggish height growth. High affinity growth hormone-binding protein (GHBP), which is identical to the extracellular domain of growth hormone (GH) receptor, is present in the human sera. We have determined GHBP activity in two cases of poorly controlled IDDM with low height velocity in relation to metabolic control in order to determine the mechanism of resistance to GH in this condition, as indicated by low levels of GH-dependent growth factor IGF-I in the face of high serum GH levels. GHBP activity was within the normal range in two cases of IDDM with slow height velocity, low IGF-I and high hemoglobin-A1. In both cases, improved blood sugar control normalized IGF-I to result in accelerated height velocity without a major change in GHBP levels. These results may indicate either normal peripheral GH receptor or normal free portion of serum GH, and may suggest that the major defect in slow growth in poorly controlled diabetes is due to the post GH receptor.

Prolonged juvenile hypothyroidism results in a permanent loss in height that is related to the duration of thyroxine deficiency before adequate thyroxine replacement treatment. A 13 year old girl with severe juvenile hypothyroidism was studied prospectively. She had an undetectable serum thyroxine concentration, a height SD score of -6.6 SD, and a bone age of 5.8 years. The enlarged pituitary gland involuted with thyroxine treatment to produce an empty sella. In addition to thyroxine the girl was treated with a gonadotrophin releasing hormone agonist to avoid the progression of puberty for 18 months and with growth hormone to achieve normal adult height.

We studied 17 short prepubertal children, aged 7.5 to 17.0 years (mean +/- SD: 11.7 +/- 2.4) more than 2.0 SD below the mean height for their age and of delayed bone age (M +/- SD: 8.1 +/- 2.3), to clarify their physiological GH secretory status. The mean concentration of GH (MCGH) was calculated and was compared with the subjects' GH responses to insulin and arginine tolerance tests (IATT) and plasma somatomedin-C (SM-C). The mean 24-h MCGH value was 3.2 +/- 1.3 ng/ml (range 1.6-5.5). The mean peak GH response to the IATT was 13.0 +/- 7.5 ng/ml (range 2.4-33.9). In addition to the two patients with abnormally low GH responses to the IATT, seven with normal responses showed low 24-h MCGH values, a small number of GH pulses and low mean GH amplitude. The mean plasma SM-C in all patients was 0.60 +/- 0.20 U/ml. This was significantly lower than that of age-matched children of normal height (p less than 0.001). The 24-h MCGH was significantly correlated with plasma SM-C levels (r = 0.51, p less than 0.05) and with that of the first three hours of sleep at night (r = 0.84, p less than 0.01). These results indicate that: 1) some short children with normal GH response to pharmacological tests secrete a low amount of GH physiologically and 2) blood sampling during the first three hours of sleep as well as 24-hour sampling is suitable in evaluating the physiological secretion of GH.