Optimum Angle of Force Production Temporarily Changes Due to Growth in Male Adolescence.

The peak increase in lean mass in adolescents is delayed from peak height velocity (PHV), and muscle flexibility temporarily decreases as bones grow. If the decrease in muscle flexibility is caused by muscle elongation, the relationship between the exerted torque and the joint angle could change in adolescents. The purpose of this study was to investigate the change in the optimum angle of force production due to growth. Eighty-eight healthy boys were recruited for this study. Isokinetic knee extension muscle strength of the dominant leg was recorded. The outcome variable was the knee flexion angle when maximal knee extension torque was produced (optimum angle). The age at which PHV occurred was estimated from subjects' height history. We calculated the difference between the age at measurement and the expected age of PHV (growth age). A regression analysis was performed with the optimal angle of force exertion as the dependent variable and the growth age as the independent variable. Then, a polynomial formula with the lowest p-value was obtained. A significant cubic regression was obtained between optimum angle and growth age. The results suggest that the optimum angle of force production temporarily changes in male adolescence.

Noggin and basic FGF were implicated in forebrain fate and caudal fate, respectively, of the neural tube-like structures emerging in mouse ES cell culture.

We developed neural tube-like structures accompanying neural crest-like cells by treating embryonic stem (ES) cells with retinoic acid. The structures contained pseudostratified Nestin+Vimentin+ neuroepithelial cells surrounded by Masson staining+ basement membrane. betaIIItubulin+Synaptophysin+ mature neurons and glial fibrillary acidic protein (GFAP)+ glial cells dispersed outside of the membrane. Addition of Noggin to the culture induced prominent proliferation of the neuroepithelial cells, leading to epithelial hyperstratification of the structures. mRNAs of transcription factors essential for forebrain development such as Emx1/2 and Pax6 were specifically expressed and Islet1+Lim1/2- motoneurons appeared by the addition of Noggin. In contrast, basic fibroblast growth factor (bFGF) promoted enlargement of central lumen and elongation of the structures. mRNAs of caudal markers, Gbx2, Cdx2 and Hoxb4/9 were expressed and Lim1/2+ spinal motoneurons appeared by the addition of bFGF. Addition of BMP-4 similarly brought about mild enlargement of central lumen of the structures. Interestingly, the addition of BMP-4 induced Slug+ neural crest-like cells surrounding the tube-like structures. mRNAs of Snail and dHand, other markers for neural crest cells, were also expressed by the addition of BMP-4. These results suggest that Noggin lead the neural-tube like structures to forebrain fate, whereas bFGF was involved in the caudalization. BMP-4 was implicated in emergence of the neural crest-like cells. Differentiation of ES cells by the present methods may mimic neurulation and subsequent neural development of early embryos, and elucidates the opposite effects of Noggin and bFGF for the neural tube development.

The persistence of an open anterior fontanel in a 4-year-old girl.

CASE REPORT: A 3-year-old girl was transferred to our hospital with a history of persistent open anterior fontanel. The patient was conscious and had no neurological deficits. Upon arrival, the patient appeared normal for her age and had no defects or anomalies other than the aforementioned lesion. The initial skull X-ray and CT were significant for a 20-mm open anterior fontanel. All other findings were normal. OUTCOME: After a follow-up period of 1.5 years, the anterior fontanel was still open, with a slight decrease in size to 15 mm. Delayed closure of the anterior fontanel without intracranial hypertension is associated with various disorders. The pathogenesis of the current patient's condition is unclear. Due to the patient's normal appearance and stable neurological status, we will follow her conservatively for any changes in condition.

Anatomical and functional recovery by embryonic stem cell-derived neural tissue of a mouse model of brain damage.

We have treated undifferentiated mouse embryonic stem (ES) cells with all-trans retinoic acid (RA) to induce differentiation in vitro into neuron-like cells with good cell viability for use as a graft. Furthermore, we asked whether the RA-induced neuron-like cells restored neurological dysfunction. To this end, the cells were transplanted into right hemiplegia model of mice, developed by a cryogenic injury of motor cortex. Motor function of the recipients was gradually improved, whereas little improvement was observed in control mice. The lesion showed clustering of mature and almost mature neuron-like cells in mice transplanted with the RA-treated cells. The grafted cells had synaptic vesicles. This finding may suggest their maturation and synaptic connection in the recipient brain. Even though further study is necessary to elucidate molecular and cellular mechanisms responsible for the functional recovery, we consider that the ES cells may have advantage for use as a donor source in various neurological disorders including motor dysfunction.

Transplantation of motoneuron-enriched neural cells derived from mouse embryonic stem cells improves motor function of hemiplegic mice.

Embryonic stem (ES) cells are expected to be a potential donor source for neural transplantation. We have obtained motoneuron-enriched neural progenitor cells by culturing mouse ES cells with retinoic acid (RA). The cells also expressed mRNA of a neurotrophic factor, neurotrophin-3 (NT-3). The left motor cortex area of mice was damaged by cryogenic brain injury, and the neural cells were transplanted underneath the injured motor cortex, neighboring to the paraventricular region. We found that the cells expressing neuronal phenotypes not only remained close to the implantation site, but also exhibited substantial migration penetrating into the damaged lesion, in a seemingly directed manner up to cortical region. We found that some of the neural cells differentiated into Islet1-positive motoneurons. It seems likely that the ability of the ES cell-derived neural progenitor cells to respond in vivo to guidance cues and signals that can direct their migration and differentiation may contribute to functional recovery of the recipient mice. We found that an "island of the mature neuronal cells" of recipient origin emerged in the damaged motor cortex. This may be associated with the neuroprotective effects of the ES cell-derived neural cells. The ES cells differentiated into CD31+ vasculoendothelial cells with the RA treatment in vitro. Furthermore, the grafted cells may provide sufficient neurotrophic factors such as NT-3 for neuroprotection and regeneration. The grafted neural cells that migrated into residual cortex and differentiated into neurons had purposefully elongated axons that were stained with anti-neurofilament middle chain (NFM) antibody. Our study suggests that motoneurons can be induced from ES cells, and ES cells become virtually an unlimited source of cells for experimental and clinical neural cell transplantation.

[Unilateral exophthalmos caused by a prolactin producing ectopic pituitary adenoma: case report].

OBJECTIVE: We report a case of a patient with a prolactin (PRL) producing ectopic pituitary adenoma presenting a unilateral exophthalmos. CASE: This 70-year-old woman presented an ophthalmologist with progressive left-sided exophthalmos over the previous 2 months. Bone window CT scan revealed extensive bony destructions of the skull base including the clivus, sphenoid sinus and medial aspect of the middle cranial fossa. Gd-DTPA MRI revealed an abnormal enhancement lesion in the sphenoid sinus, but no abnormal enhancement was seen in the sella turcica. Since these findings suggested malignant tumors of the cranial base, several biopsies through the transnasal route were carried out to confirm the diagnosis. This procedure caused the complication of cerebrospinal fluid (CSF) leakage. Because the biopsy specimen revealed a PRL producing adenoma (serum PRL-level 645.7 ng/ml), the patient was admitted to our department. On admission neurological examination showed an exophthalmos with external ocular movement disorders and disturbance of visual acuity on the left side. She underwent transsphenoidal surgery to remove the tumor and to reconstruct the sphenoid sinus and the sellar floor. Surgical exploration revealed a yellowish and soft tumor underneath the normal mucous membrane in the sphenoid sinus. The sellar floor was destructed extensively, but the dura mater of the pituitary fossa was intact except for a small pin-hole which was thought to be produced during the several biopsy procedures. No surgical procedure was applied to the intrasellar region. The sphenoid sinus was packed with a piece of fascia and fat applied with the aid of fibrin glue to prevent CSF leakage. RESULT: The patient followed a satisfactory postoperative course. Her visual acuity disturbance and exophthalmos disappeared one year after surgery. Postoperative serum PRL level remained high (66.9 ng/ml), but, subsequently, was normalized (9.5 ng/ml) with a bromocriptine therapy (15 mg daily). CONCLUSION: As far as we are aware, this is the first case report of an ectopic pituitary adenoma causing unilateral exophthalmos. Although it is extremely rare, pituitary adenomas should be kept in mind in a differential diagnosis of exophthalmos.

[A case of traumatic chiasmal syndrome presenting with bitemporal upper quadrantanopsia].

A 22-year-old woman was involved in a motor vehicle accident and suffered a craniofacial injury. The patient was treated conservatively with a diagnosis of cerebral contusion in the frontal base confirmed with MR images. When the patient regained consciousness one week after the accident, she had a complete form of bitemporal upper quadrantanopia. A bone window level CT scan showed a linear fracture in the middle of the frontal base running longitudinally and extending posteriorly down to the sella turcica and clivus. Axial MR images parallel to the optic pathway revealed a T2 bright lesion in the anterior half of the optic chiasm. The patient recovered gradually and returned to her previous life-style six months later without complaining of diplopia, but her visual field defect was left unchanged. Traumatic chiasmal syndrome is rare and usually presents bitemporal hemianopsia. Very rarely, bitemporal quadrantanopsia has been reported. Given the anatomical structure that the neural fibers from the lower nasal part of the retina run posteriorly in the optic nerve and cross the anterior half of the optic chiasm to enter the contralateral optic tract, the lesion in the optic chiasm seen in the MR images seemed to be the causative lesion of bitemporal upper quadrantanopsia in our patient. The optic chiasm appeared to be injured by a laterally stretching force exerted in an antero-posterior direction when the medial basal fracture occurred.