Evaluation of Deep Thermal Rehabilitation System Using Resonant Cavity Applicator During Knee Experiments.

This paper evaluates experiments on the knee using a new heating rehabilitation system. For effective thermal rehabilitation of osteoarthritis, it is necessary to heat the deep tissue inside the knee joint. Our new rehabilitation system is based on the re-entrant type resonant cavity applicator which was developed for deep hyperthermia treatment in our previous studies. Our experimental results using agar phantoms showed our heating system is able to heat the deep tissue inside the knee without physically contacting the surface skin. In this study, we developed a prototype applicator and experimented on a healthy human subject's knee under clinical conditions. To evaluate heating performance, we conducted heating experiments with our resonant cavity applicator and a conventional microwave diathermy system and compared the results. The experimental results of temperature increase distributions inside the human body were estimated by ultrasound imaging techniques. The estimated results from our knee experiments show that our heating system is able to heat knee tissue more deeply than microwave diathermy systems can and thus would be effective for deep thermal rehabilitation applications in clinics.

Intrauterine methylmercury intoxication. Consequence of the inherent brain lesions and cognitive dysfunction in maturity.

We studied the effects of intrauterine neurotoxicity by methylmercury (MeHg) on the postnatal developing and adult stages of rats. We used offspring delivered from dams that had been given 1 mg/kg/day methylmercury chloride for 5 pregestational days and throughout pregnancy. Histopathological examination of the brains of a proportion of the offspring on postnatal days 1 (P1) and P3 revealed degenerative neurons in the brain stem and the limbic system, including the hippocampus and the amygdala. At P7 and P14, degenerative neurons were indiscernible, but reactive astrocytosis remained in the brain stem. At P70 and P180, the brains seemed to have developed well. However, in behavioral analyses performed at 6 months of age, MeHg-exposed rats showed a significant learning disability in the passive avoidance response compared with controls, but no differences in water maze performance. Furthermore, morphometric analysis of the amygdala and hippocampus revealed significantly fewer neurons in both areas in the MeHg-exposed rats. Thus, chronic intrauterine exposure to low-dose MeHg induces a decrease in neuron population in the limbic system, and the offspring have impaired higher brain function.

Distinct pattern of neuronal degeneration in the fetal rat brain induced by consecutive transplacental administration of methylmercury.

The transplacental neurotoxicity of methylmercury (MeHg) on the fetal rat brain was studied. Adult female rats were administered 1, 2 or 3 mg/kg/day methylmercury chloride (MMC) orally for either 5 or 12 days, and were then mated. They were subsequently administered MMC in the same manner until the end of gestation. On embryonic day 22, a proportion of the fetal brains were histologically examined. Neuronal degeneration of varying degree was detected consistently in the brain stem, cingulate cortex, thalamus and cerebral basal area, including the hypothalamus. The distribution pattern of neuronal damage was different from those in rats treated with MeHg in the postnatal or adult stages. This finding suggests that pathomechanisms in MeHg intoxication operate distinctively in the fetal brain. The offspring derived from dams treated with 1 mg/kg/day MMC for 5 pregestational days and throughout pregnancy survived with inherent brain lesions. This experimental model could be a useful tool for research on the neurotoxicity of MeHg in the human fetal brain.

Process of repair in the neuroepithelium of developing rat brain during neurogenesis: chronological and quantitative observation of DNA-replicating cells.

The neuroepithelium (NE) of the cerebrum of the developing brain has been reported to 'regenerate' within a certain period after being injured. To clarify the process of repair of the NE during neurogenesis, we chronologically examined the number of cells in the neocortex, and the rate of DNA-replicating cells and the mitotic figure ratio in the NE of rats after injury. The injury was induced by transplacental administration of ethylnitrosourea (ENU), which is cytotoxic immediately after administration, to the pregnant rats on embryonic day 16. The number of living and pyknotic cells in a 220-micron width of the neocortex was evaluated in each of three groups, such as NE, subventricular zone (SVZ) + intermediate zone (IMZ) + subplate (SP), and cortical plate (CP). The 5-bromo-2-deoxyuridine (BrdU)-labeling index and the mitotic index were examined 4, 8, 16, 24, 36, and 48 h after ENU administration. Up to 16 h after ENU administration, the number of living cells per 220 microns width in the NE and SVZ + IMZ + SP decreased, but increased in CP. From 16 to 24 h, the living cell number per 220 microns width in the NE and CP was unchanged, but increased in the SVZ + IMZ + SP. From 24 to 36 h, the living cell number per 220 microns width increased in all the groups, NE, SVZ + IMZ + SP and CP. From 36 to 48 h, the living cell number per 220 microns width in the NE was unchanged, but increased in the SVZ + IMZ + SP and CP. The BrdU-labeling index reached its nadir at 8 h, but markedly increased by 16 h, and then decreased to the control level by 36 h. No mitotic figures were observed at 16 h after administration, but a significant increase in mitotic index was noted at 24 h, and after which it decreased to almost the control value by 36 h. These findings indicate: (i) that temporary arrest of neuroepithelial cell cycle occurs in the G1-phase from 4 to 8 h after ENU administration, (ii) that the cell synchronizes in the S-phase at 16 h, (iii) that a proportion of neuroepithelial cells of rat fetal neocortex at the neurogenesis stage return to neuroepithelial cell proliferation stage, to repair the NE, and (iv) that regulation of the cell kinetics of neuroepithelial cells depends on the number of cells in a certain width of NE during regeneration.

Selective involvement of large motor neurons in the spinal cord of rats treated with methylmercury.

Mercury is thought to be a possible epidemiological factor for the pathogenesis of motor neuron disease, since it has been reported that metallic, inorganic and organic mercury causes a syndrome clinically resembling amyotrophic lateral sclerosis. We administered 10 mg/kg/day methylmercury chloride to adult rats for 10 consecutive days. The hind-limbs became flaccid and atrophic, and 14 out of the 34 rats had died by the 18th day after methylmercury treatment began. Light microscopical examination of the large motor neurons in the spinal anterior horn revealed cytoplasmic vacuolation and loss of Nissl substance on the 14th day, and neuronophagia appeared on the 16th day. On the 18th day, the loss of large motor neurons was almost complete, whereas small to medium-sized neurons were preserved. Silver acetate autometallography to detect mercury revealed the selective accumulation of mercury in the large motor neurons. These findings suggest that although a high dose is required, organic mercury can cause the definite loss of large spinal motor neurons in rats.

Traumatic spinal cord injury: a neuropathological study on the longitudinal spreading of the lesions.

Eight patients died after traumatic spinal cord injuries. At autopsy, neuropathological examination revealed longitudinal spreading of cord lesions in two of these patients. One developed progressive paralysis 43 h after fracture of the fifth cervical (C5) vertebra and died 38 days after injury. Necrotic lesions extended upward to the medulla oblongata and downward to the C7 cord segment. Pencil-shaped necrosis (C7-T4) and marginal spongiosis (C7-T2) were also found. A second patient died 5 months after C5 subluxation with tetraplegia. His spinal cord was severely compressed at C4/5 and pencil-shaped necrosis, which had become partially cystic, extended upward to C3 and downward to T1; marginal spongiosis was also found in C4-C5. In both cases, complete necrosis without cell reaction was found in several cord segments, including the initially impacted segment. These findings suggest that intra- and extramedullary circulatory impairment occurred not only at the initial impact level, but also in the adjacent levels. Increased intramedullary pressure, resulting from this circulatory disturbance, in combination with a narrowed spinal canal, may induce the upward and downward spreading of the lesion.

Histologic changes in the disc after cervical spine trauma: evidence of disc absorption.

We examined the histologic changes in the disc in two cases of traumatic cervical disc herniation and compared it with previous histologic studies done in degenerative disc herniations. Differences in the absorption of herniated cartilage endplate and annulus fibrosus are also discussed. The herniated disc material was surrounded by fibrovascular tissue. Vessels in this fibrovascular tissue were seen to continue into the annulus fibrosus but not into the endplate. Scattered cartilage fragments and macrophages in the fibrovascular tissue were localized around the margin of the disc. The herniation produced a visible defect in the injured intervertebral disc. On serial sections, the amount of herniated annulus fibrosus appeared to be smaller than the defect produced in the annulus fibrosus of the injured disc. However, the herniated endplate seemed to be the same size as the defect produced in the endplate of the injured disc. Fibrovascular tissue formation, vessel infiltration into annulus fibrosus, and the presence of peripheral macrophages suggest marginal absorption. The cartilage fragments are probably remnants of disc tissue produced during the process of absorption. These findings are similar to that seen in degenerated herniated discs and suggest an absorptive process. Absorption of the annulus is more significant than absorption of the endplate.

Cervical spondylotic myelopathy. Clinicopathologic study on the progression pattern and thin myelinated fibers of the lesions of seven patients examined during complete autopsy.

STUDY DESIGN: This study was designed to reveal the progression pattern and essential histological findings of the lesions in the spinal cord affected by cervical spondylotic myelopathy. OBJECTIVES: The purpose of this study was to gain new information about symptom progression and recovery in cervical spondylotic myelopathy. SUMMARY OF BACKGROUND DATA: The characteristics of the distribution and the progression pattern of the lesions and whether demyelination and remyelination processes actually occur in cervical spondylotic myelopathy remain unclear. METHODS: Tissues from seven patients with cervical spondylotic myelopathy were taken during autopsy and examined macroscopically and microscopically. An ultrastructural examination of spinal cord from two patients was also performed. RESULTS: The anterior horn and intermediate zone of the gray matter in the compressed segments showed atrophy in all the cases and in one, atrophy was limited to these areas. Atrophy and myelin pallor in the lateral and posterior funiculi were observed in six patients, and the lateral funiculi of two were severely affected. Many thin myelinated fibers and denuded axons were demonstrated ultrastructurally in the damaged white matter of two patients. CONCLUSIONS: There appears to be a common pattern of lesion progression in cervical spondylotic myelopathy: atrophy and neuronal loss in the anterior horn and intermediate zone develop first, followed by degeneration of the lateral and posterior funiculi. Eventually, marked atrophy develops throughout the entire gray matter and severe degeneration occurs in the lateral funiculus. Furthermore, the existence of thin myelinated fibers in the white matter suggests focal demyelinating and remyelinating processes occur in cervical spondylotic myelopathy.

Corticobasal degeneration with neither argyrophilic inclusions nor tau abnormalities: a new subgroup?

In corticobasal degeneration (CBD), cerebral cortical neuronal loss with achromasia and degeneration of the subcortical nuclei, particularly the substantia nigra, are common. Recent studies have suggested that the occurrence of argyrophilic nigral inclusions, resembling the neurofibrillary tangles found in progressive supranuclear palsy, and widespread tau abnormalities may be features of CBD. We studied brain tissues from two patients in whom CBD was suspected clinically. From the distribution of their cortical and subcortical lesions, the patients were diagnosed as having CBD. However, Gallyas/tau-positive neuronal and glial structures were not found, which suggests there may be a subgroup of CBD with neither argyrophilic inclusions nor tau abnormalities.

A newly discovered age-related synaptic change in the human locus ceruleus: morphometric and ultrastructural studies.

We have recently found that in the human locus ceruleus (LC) some pigmented neurons contain granules in their cytoplasm that are immunoreactive (IR) for 38-kDa synaptic vesicle-specific protein (SVP). These represent synaptic terminals enveloped in the somatic cytoplasm. In the present study we analyzed LC pigmented neurons morphometrically in 48 autopsied individuals, whose ages at death ranged from 5 to 94 years, and also examined LC pigmented neurons ultrastructurally in 4 of these individuals. The number and incidence of LC pigmented neurons containing SVP-IR intracytoplasmic granules became significantly higher with age. The mean somatic area of the neurons was significantly higher than that of neurons without SVP-IR intracytoplasmic granules. Ultrastructurally, the synaptic terminals, which contained many round or flattened clear vesicles and sometimes dense-cored vesicles, were found to be enveloped by the somatic cytoplasm of some pigmented neurons and occasionally formed synaptic contacts with the cytoplasm. These enveloped synaptic terminals showed no apparent degenerative features. Our results strongly suggest that the enveloping of synaptic terminals by the somatic cytoplasm of human LC pigmented neurons is a phenomenon associated with the aging brain, and that this phenomenon may be related to intrinsic adaptive mechanisms of the LC pigmented neurons to certain environmental changes associated with aging.

Histologic evidence of absorption of sequestration-type herniated disc.

STUDY DESIGN: The reactions to sequestrated disc fragments, which were removed surgically from 35 patients, were examined histologically. OBJECTIVES: To elucidate whether or not there is histologic evidence of absorption of sequestrated discs. SUMMARY OF BACKGROUND DATA: Spontaneous disappearance or diminution of lumbar herniated discs in the spinal canal has been recognized, and this could be a possible explanation for relief of symptoms without surgery. The mechanism of this phenomenon is unclear. METHODS: Sequestrated discs removed surgically from 35 patients were examined histologically. RESULTS: In 30 cases, neovascularization was observed at the periphery of the sequestrated discs. Many foamy cells (macrophages) were present in the vascularized areas. In addition, immunohistochemistry revealed that many spindle-shaped, fibroblast-like cells were positive for CD68, a marker of macrophages. No fibrous scar formation was observed in any region. CONCLUSION: These findings suggest that organization is not a main course for this type of herniated disc and that a kind of "absorption" process occurs predominantly in the healing stage.

Variability of brain lesions in rats administered methylmercury at various postnatal development phases.

The effect of methylmercury chloride (MMC) on the developing rat nervous system was studied by light microscopy. Rats on postnatal day 2 (P2), P15 and P60 were administered 10 mg/kg/day MMC orally for 10 days. In newborn (after P2) rats, there was no abnormal activity or body weight loss. Young (after P15) rats showed weight loss on the 9th day after starting MMC, and subsequently unsteadiness, gait disturbance and paroxysmal convulsions appeared. In adult rats, weight loss began on the 6th day after starting MMC, and the hind-limb crossing phenomenon was induced on the 13th day. Histopathologically, minimal damage was found in the hippocampus and brainstem in newborn rats. In young rats, widespread neuronal degeneration was observed in the cerebral neocortex, CA3 and CA4 regions of the hippocampus, neostriatum, red nucleus, and various brainstem nuclei. In adult rats, neuronal damage was most extensive in the cerebellum and spinal dorsal nerve roots. These findings indicate that neuronal vulnerability to MMC exposure differs depending on the postnatal developmental stage and the brain region in the rat.

A potential use of a 123I-labelled benzodiazepine receptor antagonist as a predictor of neuronal cell viability: comparisons with 14C-labelled 2-deoxyglucose autoradiography and histopathological examination.

In the treatment and therapy of patients suffering a stroke, it is very important to predict whether viable neurones, even those of poor function, remain intact in the lesions of the brain. To determine whether viable neurones of low functional activity are represented in in vivo neuroreceptor imaging, we undertook experiments in gerbils with cerebral infarction, in which we examined histological changes and the results of dual-tracer in vivo autoradiography of glucose utilization with 14C-labelled deoxyglucose and benzodiazepine receptor binding with 123I-labelled Ro 16-0154. The unrelated findings of cerebral glucose metabolism and benzodiazepine receptor binding were observed in the primary infarct lesion and in remote areas, including the ipsilateral striatum and thalamus. Our experiments showed that when viable neurones with low functional activity remain intact, normal in vivo binding to benzodiazepine receptors is demonstrated as hypometabolism of glucose utilization. This functional, contrast-enhanced technique with 123I-labelled Ro 16-0154 may have an important role to play in the prediction of neuronal cell viability after recent brain infarction in experimental animals and humans using single photon emission tomography (SPET).

Synaptic terminals wrapped in the somatic cytoplasm of pigmented neurons in the human locus ceruleus.

We examined the locus ceruleus (LC) of 59 autopsied individuals whose ages at death ranged from 5 to 108 years. Immunocytochemistry with synaptic vesicle-specific 38-kDa protein (SVP) revealed that clusters of SVP-like immunoreactive coarse granules were present in the somatic cytoplasm of some pigmented neurons in all individuals examined. These SVP-like immunoreactive granules were confirmed electron microscopically to be contained in synaptic terminals which were wrapped in the somatic cytoplasm of pigmented LC neurons.

The anterolateral funiculus in the spinal cord in amyotrophic lateral sclerosis.

We carried out a morphometric study on the myelinated fibers in the anterolateral funiculus (ALF) and lateral corticospinal tract (LCS) in the cervical segment of the spinal cord of 13 patients with classic amyotrophic lateral sclerosis (ALS), 6 of whom had been on a respirator; 5 age-matched subjects were used as controls. The results obtained revealed that: (1) the fiber-size distributions of the myelinated fibers in the ALF and LCS of the control subjects had peaks at 2 microns; (2) there were marked and significant losses of large myelinated fibers in the ALF and LCS of ALS patients; (3) the patients who required respirator support showed more severe degeneration in the ALF than those who required none; and (4) the degree of myelinated fiber loss in the LCS did not correlate with either the illness duration or the history of respirator use.

Dysembryoplastic neuroepithelial tumor: report of a case without typical glioneuronal elements.

We studied a temporal lobe lesion found in a 44-year-old woman with a 25-year history of intractable complex partial seizures. Histologically, the lesion contained several nodular areas differing in cellular composition within the disarranged uncal cortex; in each area, neuronal and small round cells, mature ganglion cells and fibrillary astrocytic cells predominated. Ultrastructurally, the small round cells demonstrated neuronal, astrocytic or oligodendrocytic features. The astrocytic cell processes were occasionally covered by basal laminae. The mature ganglion cells had well-developed rough endoplasmic reticulum, many mitochondria and lipofuscin granules in their cytoplasm. No dense-cored vesicles were evident. We diagnosed this temporal lobe lesion as a dysembryoplastic neuroepithelial tumor (DNT), although no areas of typical glioneuronal elements with mucinous matrix were evident. This case suggests that a glioneuronal element is not always a constant feature of DNT, and that although mature ganglion cell nodules may be present, they may differ from those of gangliocytomas and gangliogliomas in lacking intracytoplasmic dense-cored vesicles. The presence of occasional astrocytic cell processes covered by basal laminae strongly suggests that some of the constituent astrocytic cells were of subpial astrocytic origin.

Evidence for transneuronal degeneration in the spinal cord in man: a quantitative investigation of neurons in the intermediate zone after long-term amputation of the unilateral upper arm.

Does transneuronal degeneration occur in the neurons of the spinal intermediate zone following degeneration of the anterior horn cells in man? To investigate this possibility, we carried out a quantitative examination of neurons in the cervical intermediate zone of a 56-year-old man who had suffered accidental amputation of the right upper arm 38 years prior to death. Recently, we reported that the cervical anterior horn cells of this patient were reduced in number not only on the amputation side but also on the spared side. The present study revealed that medium-sized neurons in the cervical intermediate zone, which were considered to be internuncial neurons, were decreased in number on both the amputation and the spared sides, but less so on the spared side. These findings indicate that retrograde transneuronal degeneration occurs in the internuncial neurons following degeneration of the anterior horn cells caused by amputation. Sequentially to this, degeneration of the commissural neurons in the intermediate zone secondary to that of the internuncial neurons may induce degeneration of the neurons in the intermediate zone and the anterior horn cells on the spared side.

Clear cell variants of intracranial tumors: meningioma and ependymoma.

We report two cases of rare histological types of intracranial clear cell tumor. Case 1: The tumor, on the left frontal convexity in a 64-year-old woman, consisted largely of polygonal cells with clear cytoplasm which were divided into lobules of uneven size by abundant fibrous connective tissue. Most of the tumor cells were immunopositive for epithelial membrane antigen and vimentin. Ultrastructurally, the tumor cells showed conspicuous interdigitations of their plasma membranes with frequent junctional complexes, and contained numerous glycogen granules in the cytoplasm and its processes. Occasionally, amianthoid collagen fibers were found in the fibrous stroma. Our diagnosis of this tumor was clear cell meningioma. Case 2: The tumor, in the right cerebellar hemisphere in a 64-year-old woman, consisted of round, clear cells with a honeycomb-like pattern. The tumor cells were positive for glial fibrillary acidic protein, vimentin and S-100 protein. Ultrastructurally, the tumor was composed of round cells arranged in a cell-to-cell pattern, and the adjacent cells often formed microrosettes containing microvilli in their lumina. There were scattered cells with accumulatios of glycogen granules in their cytoplasm. Our diagnosis of this tumor was clear cell ependymoma. From the light microscopic features of these tumors, it does not necessarily seem easy to discriminate them from other intracranial tumors composed of similar clear cells, such as oligodendroglioma, central neurocytoma, hemangioblastoma and metastic renal cell carcinoma. Ultrastructural examination is crucial in the identification of the clear cell variants of meningioma and ependymoma.