Sibling cases of a degenerative neurological disease associated with hypocupraemia and hypobetalipoproteinaemia

We describe two siblings, a boy and his younger sister, with degenerative neurological disturbances, hypocupraemia and hypobetalipoproteinaemia. The neurological features in both cases were developmental delay, dysarthria, hyperkinetics with an attention deficit, dysdiadochokinesis, night blindness, myoclonic jerks and convulsions. Their serum cooper levels did not increase despite administration of copper sulphate both orally or intravenously. The copper contents of the cultured fibroblasts in the patients were 1.5-fold that of controls.Although neurological disorders associated with abnormal copper metabolism and inherited in an X-linked manner have been previously reported, this is the first report of a neurodegenerative disease concurrent with abnormal copper metabolism and hypobetalipoproteinaemia.     

Behavior of new type of rock wool (HT wool) in lungs after exposure by nasal inhalation in rats

Objectives Previous types of rock wool has been recently replaced with high-temperature wool (HT wool). HT wool is characterized by a chemical composition with a higher concentration of Al₂O₃ and a lower concentration of SiO₂, lower biopersistence, and a higher melting point than previous types of rock wool. To evaluate the safety of HT wool, an asbestos substitute, we examined the biopersistence of HT wool in the lungs, based on changes in fiber count according to the length and fiber size (length and width), by performing a nose-only inhalation exposure study in rats. Methods Male Fischer 344 rats were exposed to fibers at the target exposure concentration of 30 mg/m³ continuously for 3 hours daily for 5 consecutive days. Rats were sacrificed shortly after exposure, and 1, 2, and 4 weeks after exposure, and their lung tissues were incinerated at a low temperature. Then, fiber counts and sizes in the lungs were analyzed using a phase contrast microscope. Results The fiber count in the lungs 4 weeks after exposure significantly decreased from the baseline value (shortly after exposure). The half-life of fibers calculated from the approximation curve was 34 days for all fibers and 11 days for fibers longer than 20 μm. Conclusions Both the length and width significantly decreased 4 weeks after exposure, probably because fibers were ingested by alveolar macrophages, discharged to outside of the body by mucociliary movement, or lysed by body fluid. In future studies, it is necessary to examine the long-term persistence of fibers in the lungs.     

Sleep disturbance in patients with developmental disability

Many patients with developmental disabilities exhibit various types of sleep disturbance. However, we have no idea of a specific approach to relieve the symptoms on sleep disturbance, although recent basic neuroscience has provided many novel findings on the neuronal mechanisms of the sleep-wakefulness cycle. In this brief review, a flip-flop circuit was introduced to explain neuronal mechanisms of the abrupt change between sleep and wakefulness. The rate of atonia during non-REM sleep was also introduced, as this index may useful for assessing the cholinoaminergic balance of the central nervous system. Sleep hygiene was also based on basic sleep-wakefulness mechanisms. To maintain sleep hygiene is a fundamental approach caring for patients with sleep disturbance, and specific approaches such as medication and treatment of sleep disordered breathing should also be based on the basic mechanisms of the sleep-wakefulness cycle. It was emphasized that effective intervention should only occur after the careful assessment of neuronal background of each patient.     

Clinicopathologic features of villoglandular papillary adenocarcinoma of the uterine cervix

OBJECTIVES: The objectives of this study are to analyze the clinicopathologic features of villoglandular papillary adenocarcinoma (VGPA) of the uterine cervix and to discuss the management thereof. We examined 13 patients with VGPA. METHODS: Clinical profiles, including patient age, clinical stage, surgical procedure, and outcome, were recorded. Pathologically, macroscopic features, polypoid tumor size, horizontal spread and depth of endophytic tumor, nuclear atypicality, mitotic count, lymph capillary space invasion, and lymph node metastasis were investigated. RESULTS: The median age of 13 patients was 45 years, with 10 and 3 patients staged Ib and IIb, respectively. All the patients underwent hysterectomy and pelvic lymphadenectomy and are alive without recurrence. Macroscopically, the tumor showed a polypoid pattern in 8 patients and a flat pattern in the remaining 5 patients. Polypoid tumor size ranged between 4 x 2 and 20 x 15 mm. Horizontal spread and depth of endophytic tumor ranged between 8 and 30 mm and between 3 and 11 mm, respectively. The tumor in all the 13 patients except 1 showed moderate nuclear atypicality. The mean mitotic count was 43/10 high-power fields. Lymph capillary space invasion was present in 4 patients, 1 of whom also had bulky lymph node metastases. CONCLUSIONS: VGPA has been reported to rarely involve lymph capillary space invasion or lymph node metastasis, leading some surgeons to conduct less radical surgeries such as conization. Nevertheless, we encountered patients with these pathologic risk factors. Much caution should be exercised in managing patients with VGPA.     

Three-dimensional probabilistic anatomical cranio-cerebral correlation via the international 10-20 system oriented for transcranial functional brain mapping

The recent advent of multichannel near-infrared spectroscopy (NIRS) has expanded its technical potential for human brain mapping. However, NIRS measurement has a technical drawback in that it measures cortical activities from the head surface without anatomical information of the object to be measured. This problem is also found in transcranial magnetic stimulation (TMS) that transcranially activates or inactivates the cortical surface. To overcome this drawback, we examined cranio-cerebral correlation using magnetic resonance imaging (MRI) via the guidance of the international 10-20 system for electrode placement, which had originally been developed for electroencephalography. We projected the 10-20 standard cranial positions over the cerebral cortical surface. After examining the cranio-cerebral correspondence for 17 healthy adults, we normalized the 10-20 cortical projection points of the subjects to the standard Montreal Neurological Institute (MNI) and Talairach stereotactic coordinates and obtained their probabilistic distributions. We also expressed the anatomical structures for the 10-20 cortical projection points probabilistically. Next, we examined the distance between the cortical surface and the head surface along the scalp and created a cortical surface depth map. We found that the locations of 10-20 cortical projection points in the standard MNI or Talairach space could be estimated with an average standard deviation of 8 mm. This study provided an initial step toward establishing a three-dimensional probabilistic anatomical platform that enables intra- and intermodal comparisons of NIRS and TMS brain imaging data.     

Cytokines modulate cilomilast response in lung fibroblasts

Fibroblasts, as a major source of extracellular interstitial connective tissue matrix, play an important role in wound healing and the development of fibrosis. The phosphodiesterase (PDE) 4 inhibitor cilomilast inhibits fibroblast chemotaxis and fibroblast-mediated gel contraction. Using the Boyden blindwell chamber chemotaxis assay and the type I collagen gel contraction model, this study investigated whether specific cytokines modulate cilomilast's inhibitory effect through regulation of endogenous PGE(2) production. Human recombinant IL-1beta stimulated PGE(2) production and shifted the cilomilast concentration-dependence curve to the left in both assay systems, indicating increased sensitivity to cilomilast. In contrast, human recombinant IL-4 inhibited PGE(2) production and shifted the cilomilast concentration-dependence curve to the right in both systems. In summary, the inhibitory effect of cilomilast on fibroblast migration and collagen gel contraction is modulated by IL-1beta and IL-4 through regulation of PGE(2) production.     

Cortical activation in area 3b related to finger movement: an MEG study

To evaluate cortical activation reflecting sensory feedback after finger movement, we recorded movement-related cerebral fields (MRCFs) following voluntary finger movement and somatosensory evoked fields for mixed (median) and pure cutaneous (radial) nerve stimulations (mSEFs and rSEFs) in six normal subjects. Equivalent current dipoles for movement-evoked field 1 (MEF1) in MRCFs and the component (70m) obtained in mSEFs, not clearly in rSEFs, were similarly distributed in each subject. They were located in area 3b, but both mean locations were significantly (p < 0.01) medial to N20m in mSEFs. MEF1 and 70m reflect similar cortical activities related to finger movement and have the same neuronal generator in area 3b, which is different from that of N20m.