Clinical trial: oral zinc in hepatic encephalopathy.

BACKGROUND: Hepatic encephalopathy has a negative effect on patient health-related quality of life (HRQOL). Zinc supplementation has been effective with regard to altered nitrogen metabolism. AIM: To investigate the effectiveness of oral zinc supplementation on hepatic encephalopathy and HRQOL. METHODS: Seventy-nine cirrhotic patients with hepatic encephalopathy were randomized to receive 225 mg of polaprezinc in addition to standard therapies of a protein-restricted diet including branched-chain amino acid and lactulose, or to continue only standard therapies for 6 months. The change of HRQOL by Short Form-36, hepatic encephalopathy grade, laboratory parameters, and neuropsychological (NP) tests were compared at baseline and at 6 months. We also evaluated via multivariate analysis whether zinc supplementation and clinical variables correlated with the changes in physical component scale (PCS) and mental component scale (MCS) between the two visits. RESULTS: Zinc supplementation significantly improved the PCS (P = 0.04), but not the MCS (P = 0.95). Zinc supplementation significantly decreased hepatic encephalopathy grade and blood ammonia levels (P = 0.03 and P = 0.01), and improved Child-Pugh score and NP tests compared with standard therapy (P = 0.04 and P = 0.02). In multivariate analysis, zinc supplementation was significantly associated with improvement in PCS (P = 0.03), whereas it was not significantly associated with change in MCS (P = 0.98). CONCLUSION: Zinc supplementation is effective in hepatic encephalopathy and consequently improves patients HRQOL.

Effect of vitamin C on common cold: randomized controlled trial.

OBJECTIVE: To investigate the relationship between the common cold and vitamin C supplementation. DESIGN: A double-blind, 5-year randomized controlled trial. SETTING: A village in Akita prefecture, one of the regions in Japan with the highest mortality from gastric cancer. SUBJECTS: Participants in annual screening programs for circulatory diseases conducted under the National Health and Welfare Services Law for the Aged, and diagnosed as having atrophic gastritis. Of the 439 eligible subjects, 144 and 161 were assigned to receive 50 or 500 mg of vitamin C, respectively, after protocol amendment. During the supplementation phase, 61 dropped out, and 244 completed the trial. INTERVENTION: Daily vitamin C supplementation of 50 mg (low-dose group) or 500 mg (high-dose group). RESULTS: Total number of common colds (per 1000 person-months) was 21.3 and 17.1 for the low- and high-dose groups, respectively. After adjustment for several factors, the relative risks (95% confidence interval (CI)) of suffering from a common cold three or more times during the survey period was 0.34 (0.12-0.97) for the high-dose group. No apparent reduction was seen for the severity and duration of the common cold. CONCLUSION: A randomized, controlled 5-year trial suggests that vitamin C supplementation significantly reduces the frequency of the common cold but had no apparent effect on the duration or severity of the common cold. However, considering several limitations due to protocol amendment, the findings should be interpreted with caution.

Developmental changes in the expression of growth-associated protein-43 mRNA in the monkey thalamus: northern blot and in situ hybridization studies.

The expression of growth-associated protein-43 has been related to axonal elongation and synaptic sprouting. Using the Northern blot analysis, we investigated the developmental changes of growth-associated protein-43 mRNA in the thalamus of macaque monkeys. The amount of growth-associated protein-43 mRNA was high at embryonic day 125, and decreased at postnatal day 1. It increased again at postnatal day 8, reached its peak value at postnatal days 50-70, and then decreased gradually until postnatal year 1. We previously reported that the amount of growth-associated protein-43 mRNA in the cerebral cortex decreased roughly exponentially during perinatal and postnatal periods and that it approached the asymptote by postnatal day 70 [Oishi T, Higo N, Umino Y, Matsuda K, Hayashi M (1998) Development of GAP-43 mRNA in the macaque cerebral cortex. Dev Brain Res 109:87-97]. The present findings may indicate that extensive synaptic growth of thalamic neurons continues even after that of cortical neurons has finished. We then performed in situ hybridization to investigate whether the expression level of growth-associated protein-43 mRNA was different among various thalamic nuclei. In the infant thalamus (postnatal days 70-90), moderate to intense expression of growth-associated protein-43 mRNA was detected in all thalamic nuclei. Quantitative analysis in the infant thalamus indicated that the expression levels were different between the nuclear groups that are defined by the origin of their afferents. The expression in the first order nuclei, which receive their primary afferent fibers from ascending pathways [Guillery RW (1995) Anatomical evidence concerning the role of the thalamus in corticocortical communication: a brief review. J Anat 187 (Pt 3):583-592], was significantly higher than that in the higher order nuclei. While moderate expression was also detected in the adult dorsal thalamus, the expression in the first order nuclei was almost the same as that in the higher order nuclei. Thus, the in situ hybridization experiments indicated that the transient postnatal increase in the amount of growth-associated protein-43 mRNA, which was shown by the Northern blot analysis, was mainly attributed to enhanced expression in the first order nuclei during the postnatal period. This may be a molecular basis for environmentally induced modification of thalamocortical synapses.

[Negative pleural cytology after intrapleural perfusion hyperthermo-chemotherapy for malignant pleural effusion].

We gave intrapleural perfusion hyperthermo-chemotherapy to a 72-year-old woman in whom malignant pleural effusion developed after surgery for primary cancer. This procedure involved irrigating the pleural space for 2 hours with a water solution at 42-43 degrees containing 240 mg cisplatin using specially devised extracorporeal circuits. Thoracoscopy was used to examine the intrapleural cavity and to place the catheters for perfusion. The patient had an uneventful postoperative course and was discharged for hospital on the second postoperative day. Thereafter, she experienced good quality of life with negative pleural cytology. Unfortunately, the patient died 3 months after the therapy, but the cause of death was unknown and there was no cancer recurrence. This technique may be safe and feasible for controlling malignant effusion to preserve quality of life, although the survival benefit has not yet been clarified.

Gamma knife surgery for epilepsy related to hypothalamic hamartomas.

OBJECTIVE: Drug resistant epilepsy associated with hypothalamic hamartoma (HH) can be cured by microsurgical resection of the lesion. Morbidity and mortality risks of microsurgery in this area are significant. Gamma Knife Surgery's (GKS) reduced invasivity seems to be well adapted. In view of the severity of the disease and risks of surgical resection it is crucial to evaluate GKS for this indication. A first retrospective study has shown a very good safety and efficacy level but for a more reliable evaluation a prospective study would be required. METHODS: Between Oct 1999 and July 2002, 30 patients with HH and associated severe epilepsy were included. Seizure semiology (video EEG) and frequency, behavioural disturbances, neuropsychological performance, endocrinological status, sleep electroclinical abnormalities, MR imaging, and visual function were systematically evaluated before and after GKS (6, 12, 18, 24, 36 months). Twenty patients had experienced precocious puberty at a median age of 3,7 (0-9). Range of maximum diameter was from 7,5 to 23 mm with only 3 larger than 18 mm. The median marginal dose was 17 gy (14-20). RESULTS: Sufficient follow up for final evaluation is not yet available. Only 6 patients have a follow-up of more than 12 months and 19 more than 6 months. However a lot of very dramatic changes did occur during that period in this group. Among the 19 patients with more than 6 months of follow-up, a lot had already experienced an increase of gelastic seizures around 3 months (3), an improvement in their seizure rate (18), behaviour (9), sleep (3), and EEG background activity (3), a cessation of partial complex seizures (7). No complications have occurred till now except one patient experiencing at 5 months a hyperthermia without infection and concomitant increase of gelastic seizures both ceasing suddenly and spontaneously after 15 days. CONCLUSION: Our first results indicate that GKS is as effective as microsurgical resection and very much safer. GKS also allows to avoid the vascular risk related to radiofrequency lesioning or stimulation. The disadvantage of radiosurgery is its delayed action. Longer follow-up is mandatory for a serious evaluation of the role of GKS. Results are faster and more complete in patients with smaller lesions inside the 3rd ventricle (grade II). The early effect on subclinical discharges turns out to play a major role in the dramatic improvement of sleep quality, behaviour, developmental acceleration at school.

Neuropathological analysis in spinal muscular atrophy type II.

We performed a neuropathological analysis, including in situ nick end labeling (ISEL) and immunohistochemistry, of two cases of clinicogenetically confirmed infantile spinal muscular atrophy (SMA) type II. Both cases showed severe reduction of the motor neurons and gliosis in the spinal cord and brain stem, although the occurrences of central chromatolysis and ballooned neurons were not frequent. Clark's and lateral thalamic nuclei, which are usually altered in SMA type I, were spared, whereas Betz cells in the precentral gyrus and large myelinated fibers in the lateral funiculus were reduced in number. Regarding apoptosis, only the younger case demonstrated a few ISEL-positive nuclei in the dorsal horn, with reduced Bcl-x expression level in the Purkinje cells. Unlike SMA type I, the expression of neurofilaments was not disturbed and the reduction in synaptophysin expression level in the anterior horn was mild. An oxidative stress-related product was deposited in atrophic motor neurons in the spinal cord, and neurons with nuclei immunoreactive for 8-hydroxy-2'-deoxyguanosine were found in the lateral thalamus. In contrast, the expression of glial glutamate transporters was not altered. These data suggest that oxidative stress and, to a lesser extent, apoptotic cell death, but not disturbed neurofilament metabolism or excitotoxicity, may be involved in neurodegeneration in SMA type II.

[Gamma knife radiosurgery for the treatment of severe epilepsy]. / Rôle de la radiochirurgie Gamma Knife dans le traitement des épilepsies sévères.

The Gamma Knife radiosurgery is a neurosurgical approach having now demonstrated well its efficiency, its low morbidity and its comfort in the treatment of numerous neurosurgical disorders. These advantages of this type of intervention make it a method of great interest in functional neurosurgery and quite particularly in surgery of epilepsy. French experience is a pionner one in this domain. If for several years the positive evolution of the epilepsy associated to brain lesions had been noticed after the Gamma Knife radiosurgical treatment, the use of this approach in surgery of the epilepsy is systematically estimated since 1993. Data are today available concerning the surgical treatment of the epilepsies originating in temporomesiale area without occupying process, epilepsies associated to hypothalamic hamartomas and epilepsies associated to cavernous angiomas or to low grade gliomas. The quality of the epileptological result obtained in these various indications associated to a very reduced morbidity lets suppose that the Gamma Knife radiosurgery could indeed have tomorrow a place within the sample group of surgical approaches dedicated to the treatment of severe epilepsies. However, a larger number of treated patients and a more prolonged follow-up remains necessary to estimate in a more definitive way this approach.

Age- and gender-related changes in ligament components.

The age- and gender-related changes in extracellular matrix components (elastin, elastin cross-links, fibrillin, collagen and glycoprotein) and mineral components (calcium, Ca; phosphorus, P) in human lumbar yellow ligaments were investigated using samples obtained from surgical specimens. The mineral (Ca and P) contents increased with ageing (r = 0.703 and r = 0.772, respectively), whereas the contents of matrix components tended to decrease with ageing (elastin r = -0.261, elastin cross-links r = -0.213, fibrillin r = 0.494; collagen r = -0.322 and glycoprotein r = -0.143). Comparison of the male and female groups revealed that the ligament elastin content and elastin cross-links decreased in the male group, whereas the ligament collagen content decreased in the female group significantly in an age-dependent manner (r = -0.788, r = -0.753 and r = -0.721, respectively). These findings demonstrate age- and gender-related changes in mineral and matrix components (especially elastin and collagen) in the lumbar yellow ligaments in the Japanese population. It is suggested that elastin and collagen metabolism in ligaments changes both with age and according to gender.

New multiflorane-type triterpenoid acids from Sandoricum indicum.

Three new 12beta-hydroxymultiflorane triterpenoid acids, sandorinic acids A-C (1-3), were isolated from the stem bark of Sandoricum indicum together with five known triterpenes (4-8). The structures of 1-3 were elucidated by spectral data interpretation. Compounds 1-8 were evaluated for their inhibiting activity against several tumor cell lines and for their effects on lymphocyte proliferation.

Differentiation-associated Na+-dependent inorganic phosphate cotransporter (DNPI) is a vesicular glutamate transporter in endocrine glutamatergic systems.

Vesicular glutamate transporter is present in neuronal synaptic vesicles and endocrine synaptic-like microvesicles and is responsible for vesicular storage of L-glutamate. A brain-specific Na(+)-dependent inorganic phosphate transporter (BNPI) functions as a vesicular glutamate transporter in synaptic vesicles, and the expression of this BNPI defines the glutamatergic phenotype in the central nervous system (Bellocchio, E. E., Reimer, R. J., Fremeau, R. T., Jr., and Edwards, R. H. (2000) Science 289, 957-960; Takamori, S., Rhee, J. S., Rosenmund, C., and Jahn, R. (2000) Nature 407, 189-194). However, since not all glutamatergic neurons contain BNPI, an additional transporter(s) responsible for vesicular glutamate uptake has been postulated. Here we report that differentiation-associated Na(+)-dependent inorganic phosphate cotransporter (DNPI), an isoform of BNPI (Aihara, Y., Mashima, H., Onda, H., Hisano, S., Kasuya, H., Hori, T., Yamada, S., Tomura, H., Yamada, Y., Inoue, I., Kojima, I., and Takeda, J. (2000) J. Neurochem. 74, 2622-2625), also transports L-glutamate at the expense of an electrochemical gradient of protons established by the vacuolar proton pump when expressed in COS7 cells. Molecular, biological, and immunohistochemical studies have indicated that besides its presence in neuronal cells DNPI is preferentially expressed in mammalian pinealocytes, alphaTC6 cells, clonal pancreatic alpha cells, and alpha cells of Langerhans islets, these cells being proven to secrete L-glutamate through Ca(2+)-dependent regulated exocytosis followed by its vesicular storage. Pancreatic polypeptide-secreting F cells of Langerhans islets also expressed DNPI. These results constitute evidence that DNPI functions as another vesicular transporter in glutamatergic endocrine cells as well as in neurons.

Effect of a moderately energy-restricted diet on obese patients with fatty liver.

The effects of a moderately energy-restricted (25 kcal/kg) diet on liver-function tests, anthropometric measurements, mononuclear-cell phospholipid fatty acid, lymphocyte blastogenesis, and plasma prostaglandin E2 and alpha-tocopherol levels were observed at weeks 0, 8, and 24 in 14 obese patients with fatty liver. Serum aminotransferase levels were improved significantly, with decreases in the body mass index and waist circumference. Decreases in energy intake from carbohydrate and increases in intake of vitamin A, vitamin C, and vegetables were observed at week 24. In mononuclear-cell phospholipids, linoleic acid (18:2omega 6), which was significantly lower in patients than in controls at week 0, was increased at week 24. In contrast, arachidonic acid was decreased. Plasma prostaglandin E2 levels were significantly lower in patients than in controls at week 0 and increased at week 24. The mononuclear-cell response for phytohemagglutinin correlated with 18:2omega 6 in mononuclear-cell phospholipids (r = 0.692, P < 0.01). Improvement of the serum alanine-aminotransferase level correlated with an increase in the plasma alpha-tocopherol level (r = -0.667, P < 0.01) and increases in consumption of vitamin A, omega 3 polyunsaturated fatty acids, and vegetables. These findings suggest that a hypoenergetic diet rich in omega 3 polyunsaturated fatty acids and antioxidants might be beneficial for obese patients with fatty liver.

Dietary phosphorus deprivation induces 25-hydroxyvitamin D(3) 1alpha-hydroxylase gene expression.

Dietary phosphorus deprivation causes hypophosphatemia and an increase in serum 1alpha,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] concentrations. To determine the molecular mechanisms of this regulation, the effects of dietary phosphorus deprivation and hypophysectomy on 25-hydroxyvitamin D(3) 1alpha-hydroxylase (1alpha-hydroxylase) protein and messenger RNA (mRNA) expression were examined in rats. A low phosphorus diet (LPD) for 4 days resulted in hypophosphatemia and an increase in serum 1,25-(OH)(2)D(3) levels. This increase was caused by the induction of 1alpha-hydroxylase protein and mRNA expression (4- and 10-fold increases, respectively). Administration of the LPD or normal phosphorus diet to hypophysectomized (HPX) rats resulted in hypophosphatemia and suppression of 1alpha-hydroxylase gene expression, indicating that hypophosphatemia itself is not sufficient to induce 1alpha-hydroxylase mRNA expression. Administration of GH to HPX rats fed LPD could partially restore 1alpha-hydroxylase mRNA expression, whereas supplementation with insulin-like growth factor I, T(3), estrogen, or corticosterone had no effect. We also examined Phex gene expression in the bone, because the clinical features of X-linked hypophosphatemia resemble those of HPX rats. Phex mRNA expression, however, was not altered in HPX rats. In conclusion, we demonstrated that the increase in serum 1,25-(OH)(2)D(3) levels caused by dietary phosphorus deprivation is due to the induction of 1alpha-hydroxylase mRNA expression, and this increase is mediated in part by a GH-dependent mechanism.

Pumpkin peroxisomal ascorbate peroxidase is localized on peroxisomal membranes and unknown membranous structures.

To investigate the roles of peroxisomal membrane proteins in the reversible conversion of glyoxysomes to leaf peroxisomes, we characterized several membrane proteins of glyoxysomes. One of them was identified as an ascorbate peroxidase (pAPX) that is localized on glyoxysomal membranes. Its cDNA was isolated by immunoscreening. The deduced amino acid sequence encoded by the cDNA insert does not have a peroxisomal targeting signal (PTS), suggesting that pAPX is imported by one or more PTS-independent pathways. Subcellular fractionation of 3- and 5-d-old cotyledons of pumpkin revealed that pAPX was localized not only in the glyoxysomal fraction, but also in the ER fraction. A magnesium shift experiment showed that the density of pAPX in the ER fraction did not increase in the presence of Mg(2+), indicating that pAPX is not localized in the rough ER. Immunocytochemical analysis using a transgenic Arabidopsis which expressed pumpkin pAPX showed that pAPX was localized on peroxisomal membranes, and also on a unknown membranous structure in green cotyledons. The overall results suggested that pAPX is transported to glyoxysomal membranes via this unknown membranous structure.

Accumulation of magnesium as well as calcium and phosphorus in Japanese monkey arteries with aging.

To examine whether an accumulation of elements in the arteries with aging differs between human and animal, the authors investigated the relationships among element contents in the arteries of the Japanese monkeys. The Japanese monkeys consisted of five males and four females, ranging in age from 2 to 29 yr. The aorta, common and external iliac, femoral, common carotid, subclavian, and axillary arteries were resected from the monkeys and element contents were determined by inductively coupled plasma-atomic emission spectrometry. It was found that there were very high correlations between calcium and phosphorus contents, between calcium and magnesium contents, and between phosphorus and magnesium contents in all of the monkey arteries. In addition, significant correlations were found among the other element contents in some, but not all of the arteries. These results were consistent with the foregoing findings of the human arteries. It is likely that magnesium forms compounds with phosphorus or calcium in the monkey arteries.

[Acute onset of tuberculous meningoencephalitis presenting with symmetric linear lesions in the bilateral thalamus: a case report].

A 18-year-old woman was admitted to our hospital because of high fever and headache. Nuchal stiffness was present, and a CSF examination showed lymphocyte-domonant pleocytosis and a decreased level of glucose. Although antibiotics, aciclovir and an antimycotic drug were administered, disturbance of consciousness, involuntary movements, and pyramidal tract signs appeared. Soon after the medications were changed to antituberculous medicines, the meningoencephalitis started to subside, and was finally cured. Judging from the clinical findings, the CSF findings, the effectiveness of antituberculous medicines, an elevated ADA level in CSF, and positive conversion in tuberculin tests, the final diagnosis was made as tuberculous meningoencephalitis. At the severest stage of the disease, a brain MRI showed symmetric, linear lesions without the effect of Gd-enhancement in the bilateral thalamus, which thereafter disappeared along with the healing of the illness. From all these things, we conclude that thalamic and other parenchymal lesions should be kept in mind in case of acute tuberculous meningoencephalitis.

Identification of 25-hydroxyvitamin D3 1alpha-hydroxylase gene expression in macrophages.

BACKGROUND: The 25-hydroxyvitamin D3 1alpha-hydroxylase (1alpha-hydroxylase) is almost exclusively expressed in the kidney. However, 1alpha-hydroxylase activities have been observed in some extrarenal tissues, including inflammatory cells of the monocyte/macrophage lineage. In sarcoidosis, macrophage 1alpha-hydroxylase causes overproduction of 1,25-(OH)2D3, resulting in hypercalcemia. In this study, we investigated the regulation of macrophage 1alpha-hydroxylase at a molecular level. METHODS: We used the human monocytic cell line THP-1, which can be differentiated into macrophage-like cells by treatment with phorbol ester. The expression of 1alpha-hydroxylase in THP-1 cells was examined by Northern blotting and immunoblotting using an antibody raised against a synthetic peptide corresponding to the 14 C-terminal amino acids of 1alpha-hydroxylase. We investigated the regulation of 1alpha-hydroxylase mRNA expression by RNase protection assay. RESULTS: Northern blot and immunoblot analyses confirmed the expression of 1alpha-hydroxylase in THP-1 cells at the mRNA and protein levels. Although parathyroid hormone and calcitonin, known stimulators of renal 1alpha-hydroxylase, did not affect the expression of 1alpha-hydroxylase mRNA, 8-Br-cAMP (5 x 10-4 mol/L) increased the expression of 1alpha-hydroxylase mRNA in THP-1 cells (198 +/- 9%). 1,25-(OH)2D3, known as a suppressor of renal 1alpha-hydroxylase, did not affect the expression of 1alpha-hydroxylase mRNA. By contrast, 1,25-(OH)2D3 markedly increased the expression of 25-hydroxyvitamin D3 24-hydroxylase mRNA. Interferon-gamma (2000 IU/mL) increased the expression of 1alpha-hydroxylase mRNA in differentiated THP-1 cells (922 +/- 25%). CONCLUSIONS: The present results suggest that 1alpha-hydroxylase activity in macrophages is mediated by the same enzyme as in kidney. Interferon-gamma treatment increases macrophage 1alpha-hydroxylase levels via directly increasing gene expression of this enzyme.

Effects of three-month oral supplementation of beta-carotene and vitamin C on serum concentrations of carotenoids and vitamins in middle-aged subjects: a pilot study for a randomized controlled trial to prevent gastric cancer in high-risk Japanese population.

Prior to a randomized controlled trial to prevent gastric cancer by oral supplementation of beta-carotene and vitamin C in a high-risk Japanese population, we examined the serum response to three-month oral supplementation of beta-carotene (0, 3, 30 mg / day) and vitamin C (0, 50, 1000 mg / day) by a three-by-three factorial design using 54 subjects (age range = 40 - 69 years). Serum concentrations of carotenoids, alpha-tocopherol, and ascorbic acid were examined at baseline, and one, two, and three-month points. Both serum beta-carotene and ascorbic acid were significantly higher in high-dose groups than in each placebo group during the supplementation. The serum beta-carotene increased gradually (597 - 830% increase) during the study, whereas the serum ascorbic acid reached nearly a steady-state at the one-month point and remained stable thereafter (88 - 95% increase). No statistically significant interaction between beta-carotene and vitamin C supplementations was observed either for serum beta-carotene or for serum ascorbic acid. Among carotenoids and alpha-tocopherol examined, serum lycopene in the high-dose beta-carotene group was significantly higher than in the placebo group at all points. No unfavorable change in carotenoids and alpha-tocopherol was observed in any group.

Cytotoxic alkaloids of Pachysandra terminalis.

Four steroidal alkaloids, epipachysamines B (1) and E (2), pachystermine A (3) and pachysamine E (4), were isolated as cytotoxic principles from the MeOH extract of the stems of Pachysandra terminalis SIEB. et ZUCC. (Buxaceae). These alkaloids showed cytotoxic activity against P388 and P388/ADR leukemia cells in vitro. Three of the alkaloids (1-3) were previously isolated from this plant material, and this is the first report of their cytotoxic activity. Pachysamine E (4) is a new alkaloid.

Postmortem study of ataxia with retinitis pigmentosa by mutation of the alpha-tocopherol transfer protein gene.

A new syndrome of ataxia and retinitis pigmentosa with vitamin E deficiency caused by the missense mutation of alpha-tocopherol transfer protein (alpha-TTP) gene was recently proposed. After studying the first postmortem case with this mutation pathologically and biochemically, whether the symptoms can be treated by supplementation of vitamin E or not is discussed. The major pathological findings were retinal atrophy; severe dying back-type degeneration of the posterior column; and massive accumulation of lipofuscin in neurons including dorsal root ganglion (DRG) cells, which were almost identical to those in vitamin E deficient animals and patients with fat malabsorption. Also, mild loss of Purkinje cells was noted. Because robust expression of alpha-TTP was detected in the cerebellum as well as in the liver and the tissue concentration of vitamin E in the cerebellum was still low even after oral supplementation, the mild Purkinje cell loss might be related to the mutant alpha-TTP in the cerebellum. By contrast, in the DRG, thought to be mainly responsible for ataxia, no expression of alpha-TTP was detected, and the tissue concentration of vitamin E increased to normal after supplementation. It is therefore considered that oral supplementation of vitamin E should effectively counteract the progression of ataxia.

The cerebellar and thalamic degeneration in Fukuyama-type congenital muscular dystrophy.

We report a male autopsy case of Fukuyama-type congenital muscular dystrophy (FCMD), with unusual neuropathological findings. The patient was a Japanese man aged 26 years at the time of death. He had shown severe psychomotor retardation and muscular dystrophy since early infancy, and was diagnosed as having FCMD at the age of 5 years. He died of respiratory failure. The main neuropathological finding was extensive cerebral and cerebellar cortical dysplasia, characteristic of this disorder. In addition, degeneration of the cerebellar efferent pathway, including the dentate nucleus, superior cerebellar peduncle, and red nucleus, and that of the lateral thalamic nucleus were observed. These findings suggest the possibility that the long survival can clarify the latent neurodegeneration in the cerebellum and thalamus in FCMD, in addition to congenital malformations. The system degeneration should be carefully evaluated in the pathological examination of this disorder.