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A family with adrenoleukodystrophy and clinical manifestations of spinocerebellar degeneration was studied. Two adult male first cousins showed progressive limb and truncal ataxia, slurred speech and spasticity of the extremities. Brain CT scans demonstrated atrophy of the pons and cerebellum, in both cases. Very long chain fatty acids in plasma and erythrocyte membranes were elevated in the affected patients and intermediately increased in an aunt and the mother of one patient, thereby indicating homozygotes and carriers of adrenoleukodystrophy, respectively. This unusual type of adrenoleukodystrophy seems to be transmitted as an X-linked recessive trait.

The rat anterior pituitary was cultivated by means of organ culture technique. The prolactin secretion in this gland was maintained or rather accelerated during 12 days cultivation. This means that the rat anterior pituitary can secrete prolactin under complete deprivation of hypothalamic control. Gonadotropin secretion was declined under the same culture condition.

A report is presented on biochemical studies of the fibroblasts from a 26-year-old man with Fabry's disease whose clinical picture was atypical. The patient had severe pain in the extremities, but no angiokeratomas, corneal clouding or hypohidrosis. The trihexosylceramidase activity in the fibroblasts in vitro was deficient. The level and Km value of the residual activity were similar to levels seen in typical Fabry's patients. However, fibroblasts from the patient cultured in medium supplemented with [3H]ceramide trihexoside hydrolyzed the labeled ceramide trihexoside much higher than did cells from typical Fabry's patients, implying that the patient has a partial defect in hydrolysis of trihexosylceramide in cultured fibroblasts.

During the past few years, bone marrow transplantation (BMT) has been performed for various lipidoses in both human patients and animal models (1–8). Most patients transplanted for lipidoses suffered from the non-neuropathic form of Gaucher’s disease. Since in this type of Gaucher’s disease the reticuloendothelial system is involved, possible beneficial effects of BMT may be explained by replacement of the Gaucher cells by enzymatically competent, donor-derived cells, since after BMT not only the blood cells, but also the tissue macrophages are being replaced by donor derived cells (9). Recently, improved psychomotor development has been reported in patients with metachromatic leukodystrophy (3, 4). The neurological improvement following BMT in these patients cannot be explained easily, since the blood-brain barrier prevents circulating enzyme to enter brain tissue (10), and the presence of donor-derived cells, which contribute to the increased enzyme activity in e.g. lung and liver tissue (11–12) , has not been reported in brain tissue so far. Preliminary studies in a patient with Niemann-Pick type B disease showed clinical improvement following BMT, but the long-term effects are not evaluable yet (13). In a mouse model for Niemann-Pick disease, BMT did not result in clinical improvement, despite decreased accumulation of sphingomyelin in liver and spleen (6).

We treated two patients with adrenoleukodystrophy (ALD) with a diet that contained 0.636% lipids as soybean oil, and less than 0.01% of the total fatty acids were very-long-chain fatty acids (VLCFA). Although clinical improvement was not evident in either patient, the VLCFA levels of erythrocyte membranes and plasma decreased in patient 1; in particular, the C25:0 in erythrocyte membranes became normal. Therefore, the abnormal accumulation of VLCFA in ALD arises partially from the diet. The VLCFA-free diet should be beneficial in ALD.

The metabolism of ceramide trihexoside (CTH) was studied in cultured skin fibroblasts from Fabry's patients, carriers, and controls. The in vitro activities of alpha-galactosidase in fibroblasts using either artificial substrate or CTH led to a clear identification of 4 Fabry's patients, 6 carriers and 8 controls. Normal findings were noted in one carrier. In fibroblasts from Fabry's patients, the residual activities assayed with CTH were less than those with the artificial substrate. In the CTH-loading test, the incorporation and hydrolysis of CTH in the fibroblasts were closely related with the culture time and CTH-concentration in the medium. With 0.5 nmol CTH per flask (25 cm2 growth area, 3 ml of medium), the hydrolysis rate of CTH, based on its incorporation, was 2.1% in fibroblasts from 4 Fabry's patients, 82.0% in 10 controls and 47.1% in 6 out of 7 carriers on the 7th day of culture. The impaired hydrolysis in carriers' fibroblasts differs from the hydrolysis noted in fibroblasts from carriers of autosomal recessive sphingolipidoses with a normal hydrolysis. These findings explain that some of the carriers show clinical symptoms and a mild accumulation of CTH in their tissues, such as seen in Fabry's patients. In one carrier there was a normal hydrolysis of CTH, both in vitro and in the CTH-loading study. This may be explained by Lyon's random X-chromosome inactivation theory.

Globoid cell leukodystrophy (Krabbe’s disease, GLD) is a neurological dijogder of infancy caused by a genetic deficiency of galactosyl-ceramidase I.1,2 The murine analogue is twitcher mouse, in which galactosyl-ceramidase I is also deficient.3,4 The pathological features are similar to those of human GLD. In both, severe demyelination occurs in central and peripheral nervous tissues. In addition, gliosis, loss of oligodendrocytes, and presence of globoid cells are evident in the white matter. Galactosylceramide, a natural substrate of the deficient enzyme, apparently does not accumulate in the nervous tissues of human and murine cases of GLD. In 1972, Miyatake and Suzuki6 found that the hydrolysis of galactosylsphingosine (psychosine) is impaired in tissues from GLD patients and proposed, for the pathogenesis of GLD, the “psychosine hypothesis” which postulates that the degeneration of oligodendrocytes and consequent demyelination in the GLD tissue are due to the toxicity of galactosylsphingosine. In 1980, Svennerholm et al demonstrated an abnormal accumulation of galactosylsphingosine in the brains of GLD patients and supported the hypothesis. As to the twitcher mouse, Igisu and Suzuki8 noted an accumulation of the compound, determined by fluorometric assay using TLC. In this paper, we describe a procedure for the determination of galactosylsphingosine, using HPLC, and data on galactosylsphingosine content in tissues from normal and twitcher mice. The data on normal human tissues and tissues from a patient with GLD are also described.

A combination of brain-stem auditory evoked potentials (BAEPs), short latency somatosensory evoked potentials (SEPs) and pattern reversal visual evoked potentials (VEPs), were studied in two patients with adrenoleukodystrophy (ALD) and one patient with adrenomyeloneuropathy (AMN), as well as in one female carrier of each of the respective diseases. Abnormalities in at least 1 of the 3 evoked potentials were found in every case, including the carriers of ALD and AMN. The two most common findings were prolongation of the I-V interval of the BAEP and the N13-N20 interval of the SEP. These abnormalities were recorded either alone or in combination in all 5 cases. This finding suggests delayed conduction time in the central sensory pathways in both diseases, probably due to demyelination. The remarkable result, which distinguished AMN from ALD, even in their respective carriers, was delay of the N9 latency of the SEP, indicating slowing in conduction velocity of the peripheral nerve. Multimodality evoked potentials are useful not only in raising the detection rate for abnormal findings, but also in providing additional information about the functional state of separate afferent pathways. It is also of value in detecting and differentiating the carriers of ALD and AMN.

We examined chronological changes of myelin proteins of the brainstem and spinal cord of the twitcher mouse (15, 20, and 30 days old), a murine model of human globoid cell leukodystrophy caused by a genetic deficiency of galactosylceramidase I activity. The yield of myelin was normal until postnatal day 20, whereas galactosylsphingosine (psychosine) accumulated with age in myelin. The protein profiles of myelin and the activity of 2',3'-cyclic nucleotide 3'-phosphodiesterase in the myelin remained normal throughout the experimental period. Fatty acylation of proteolipid protein (PLP) was examined in a cell-free system by incubation of myelin with [3H]palmitic acid, CoA, and ATP, and was normal at postnatal day 15, but decreased after postnatal day 20. Decreased fatty acylation of PLP was also observed in the twitcher mouse at postnatal day 20 when the isolated myelin was incubated with [14C]palmitoyl-CoA in the absence of ATP and CoA, or the slices of brainstem and spinal cord were incubated with [3H]palmitic acid. The activity of fatty acid:CoA ligase was reduced in myelin. These data suggest that decreased acylation of PLP in twitcher mouse myelin is probably due to reduced activities for both activation and transfer of fatty acid into PLP and that metabolic disturbance is present in myelin because acylation of PLP has been shown to occur in myelin membrane. Although psychosine (200 microM) inhibited only 17% of the acylation in vitro, it may be responsible for the reduced acylation of PLP in vivo.

The metabolism of galactosylceramide was investigated in normal and twitcher mice, an animal model for human globoid cell leukodystrophy. The findings were compared with data obtained on human tissues. In vitro studies demonstrated that there were two genetically distinct enzymes that hydrolyze galactosylceramide: galactosylceramidase I and II. The former was deficient in the twitcher, while the latter was intact. β-Galactosidase preparations purified from normal mouse liver possessed the activity to hydrolyze galactosylceramide when the assay conditions for galactosylceramidase II was used. Therefore, galactosylceramidase II was considered to be identical to GM1 ganglioside β-galactosidase. In contrast to the human enzyme, the murine β-galactosidase had a relatively high Km value toward galactosylceramide. The galactosylceramide-loading test demonstrated that the twitcher fibroblasts hydrolyzed the lipid at lower rates than seen in cases of human globoid cell leukodystrophy fibroblasts. These differences in galactosylceramidase II between murine and human tissues suggest that galactosylceramide accumulates in twitcher mice but not in humans with globoid cell leukodystrophy, even though galactosylceramidase I is genetically deficient in both human and this mouse model.

Abnormal accumulation of lysosulfatide (sulfogalactosylsphingosine) was evident in autopsied tissues from a boy with late-infantile metachromatic leukodystrophy. The concentration was high in the cerebral white matter, spinal cord and sciatic nerve (116-787 pmol/mg protein) and low in the cerebral gray matter, kidney and liver (4-40 pmol/mg protein). As is the case with galactosylsphingosine, lysosulfatide inhibited cytochrome c oxidase activity, in a dose-dependent manner. Judging from the tissue distribution of the accumulated lysosulfatide and because of the cytotoxicity, the lysosulfatide presumably explains the demyelination seen in the nervous tissues of patients with metachromatic leukodystrophy.

In a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes [MELAS] who had normal mitochondrial enzyme activity, high doses of coenzyme Q10 (CoQ) were administered. Clinical improvement with decreased serum lactate and pyruvate levels was observed. Though the mechanism of action of CoQ is not known, a trial is worthwhile in patients with MELAS.

Galactosylsphingosine (psychosine) in somatic organs from a patient with globoid cell leukodystrophy and from the twitcher mouse, an animal model of human globoid cell leukodystrophy was assayed. There was an abnormal accumulation of galactosylsphingosine as in nervous tissues, albeit the concentrations being lower than those in nervous tissues. Galactosylsphingosine accumulation in the kidney of the twitcher mouse increased with age. These findings indicate that globoid cell leukodystrophy is a generalized galactosylsphingosine storage disease.

The pattern of early myelination was investigated in the dorsal columns of the cervical spinal cord in the twitcher, an authentic murine model of human globoid cell leukodystrophy, and their littermates. There were no differences in the number of myelinated fibers until the day 20 postnatal. However, myelin sheath in the homozygous affected twitchers at the day 20 were thinner than those of heterozygous and normal littermates, while at the day 10 no significant differences were detected. These observations indicated that in the twitcher mouse, despite the generic deficiency of galactosylceramidase, myelination progresses normally in early stages and then hypomyelination becomes apparent before myelin breakdown.

Serum levels of fibrin degradation products (FDP) were determined using an FDP slide test (a latex agglutination reaction method) in 20 normal control women and 67 preoperative patients with ovarian tumors. In the control women the FDP levels were 2.5 μg/ml or lower. In the 14 patients with ovarian retention cysts including endometrial cysts the FDP levels were normal (2.5 μg/ml or lower). In the 40 patients with benign ovarian neoplasmas, 37 (93%) showed normal FDP levels. On the contrary, in the 12 patients with malignant ovarian tumors, abnormally high levels of FDP were observed in 9 cases (75%). These observations revealed that the preoperative measurements of serum FDP contributed to the preoperative diagnosis of malignant ovarian tumors.

The lipid and protein composition of erythrocyte membranes from patients with Duchenne muscular dystrophy was studied. When compared with age and sex-matched controls, no significant change was observed in the content of cholesterol and phospholipid, phospholipid components and their fatty acid composition, though the lipid content and fatty acid distributions were different between adult and child controls. The protein distribution on SDS-acrylamide gel electrophoresis was identical for Duchenne patients and controls.

The effects of HMG (Humegon)-HCG therapy in 6096 cycles in 2166 Japanese women with anovulatory infertility were examined. The rates of ovulation, pregnancy, the ovarian hyperstimulation syndrome, multiple pregnancy, abortion, and malformations in the newborn were recorded, and the possible factors of multiple pregnancies were analyzed. Ovulation occurred in 73.2% of the cases and 64.5% of the treatment cycles. Pregnancy occurred in 23.0% of the cases and 8.6% of the cycles. Ovarian hyperstimulation syndrome with grade I of WHO definition or more was observed in 10.3% of the cases and 5.3% of the cycles. The incidence of the ovarian hyperstimulation syndrome was high in amenorrheic patients, who respond to progestin with bleeding. The multiple pregnancy rate was 20.5%, of which 13.0% was twins and 7.5% triplets or more. The abortion rate was 22.0%, and the abortion rate in multiple pregnancy was significantly higher (P less than 0.05) than that in singleton pregnancy. The external malformation rate was 1.68% in the 594 newborn who could be examined. No significant differences were found in maternal factors, the treatment schedule, or the ovarian response to treatment in singleton and multiple pregnancy groups. This survey revealed that the efficacy and the incidence of adverse effects of Humegon-HCG therapy in a large number of Japanese women were not different from those in Caucasians except for a lower rate of multiple pregnancy, and no special causative factors for multiple pregnancy were found.

Morphological alterations occurring in Schwann cells of unmyelinated fibers (unmyelinated Schwann cells) were investigated in the sciatic nerve of the twicher mouse, a murine model of human globoid cell leukodystrophy. After postnatal day 10, the number of Schwann cell-axon units gradually increased and the number of unmyelinated axons per unit progressively decreased in the twitcher mouse. However, the total number of unmyelinated axons showed no significant differences between twitcher and normal mice. Thus, these alterations of unmyelinated Schwann cells in the twitcher mouse suggest that attenuated branching of cellular processes develops at an early stage and progresses together with progression of demyelination in this mutant.

Galactosylceramidase activity in whole homogenates of clipped tails could be used successfully to determine the genetic status of the twitcher mouse, a newly discovered neurological mutant caused by a galactosylceramidase deficiency. Normal, heterozygous, and affected animals were clearly segregated at 7 days. The results were consistently confirmed by galactosylceramidase assays on brain or liver tissues, development of clinical disease, or by mating experiments. For technical reasons, identification of carriers in adult mice was less clear-cut and should be avoided, whenever possible. Tail clippings of mice of different ages cannot be mixed because of normal developmental changes in the enzymatic activity. Early identification of affected mice makes it possible to study the disease process before the clinical onset. Early identification of carriers permits efficient maintenance of the breeding colony. The technique should be applicable to other mutants when the primary genetic defects are known.

A rare and instructive case of myocardial infarction in a 29-year-old woman was presented. In this case it was clinically suspected that myocardial infarction was due to metastatic choriocarcinoma of the heart. This was confirmed by autopsy. It was emphasized that metastatic choriocarcinoma of the heart could be a cause of myocardial infarction in young women.

A patient with adrenoleukodystrophy and his mother, a carrier, showed an elevated ratio of very long-chain fatty acids to long-chain fatty acids and decreased beta-galactosidase activity. Other lysosomal enzyme activities were normal except for the borderline level of arylsulfatase-A activity. However, the father and other patients with variant forms of adrenoleukodystrophy showed normal beta-galactosidase and other lysosomal enzyme activities.

Frequency of pigmentary degeneration of the retina (PDR) among patients with degenerative and heredodegenerative neurological diseases (HDNDs) was estimated based on the hospital statistics. PDR was detected in 3% of 176 inpatients with HDNDs by careful ophthalmologic examination. On the other hand, out of 30 consecutive cases of PDR seen in our Department of Neurology, 15 patients were associated with some form of HDNDs. Atypical PDR were more frequently associated with HDNDs than typical PDR. Among neurological manifestations in those 15 cases of PDR associated with HDNDs, mental deficiency, hearing disturbance, spasticity, progressive ophthalmoplegia and ataxia were most frequently encountered. Four cases with unusual symptomatology were presented. Clinical analysis of cases of PDR associated with HDNDs in the present series as well as in the relevant literature revealed an extreme variety of clinical manifestations and underlying metabolic disorders, suggesting a possible participation of multiple factors in the pathogenesis of PDR. Importance of careful ophthalmologic examination in HDNDs was stressed from the prognostic point of view.

To clarify the functional relation between the ovulation blocking-effect and the central depresant action of progesterone, electrophysiological studies were done, using unanesthetized curarized albino rats under artificial respiration, additionally using rabbits and cats, and the following results were obtained:(1) After the administration of progesterone (10-20mg/kg), EEG of the hippocampus and neocortex showed sleep patterns, lasting 1 hr.(2) Activation threshold of posterior hypothalamic stimulation upon the hippocampus and neocortex was markedly elevated after the administration of progesterone.(3) The threshold voltage of desynchronizing the hippocampal regular slow waves by anterior hypothalamic stimulation remained almost unchanged.(4) The threshold voltage of the recruiting response of the neocortex by stimulation of nucleus centrum medianum almost unchanged.From these results it is concluded that progesterone seems to suppress the activity level of the posterior hypothalamus as well as that of the limbic-midbrain area (Nauta, 1958) by which the blockade of ovulation may take place.

Hypothalamic tissues of female rats were extracted with 1.0M acetic acid. The acidic extract was lyophilized and subjected to gel filtration on Sephadex column and assayed for follicle-stimulating hormone-releasing factor (FSH-RF) activity and luteinizing hormone-releasing factor (LH-RF) activity by estimating FSH and LH using the organ culture method of rat anterior pituitaries. FSH activity was measured by the method of Steelman-Pohley, and LH activity by the method of Parlow. Gel filtration on a short column of Sephadex G-25 in 0.1M pyridine acetate provided a single fraction which showed significant FSH-RF and LH-RF activity. Each activity showed a doserelated increase. Application of a long column of Sephadex G-25 in 0.05M pyridine acetate brought about separation of a peak for FSH-RF activity from that for LH-RF activity. The former activity was eluted from the column just before the appearance of the latter. These results indicated that the secretion of FSH and LH from the rat anterior pituitary was regulated by the specific hypothalamic FSH-RF and LH-RF, respectively.

Anterior pituitary glands from normal female rats were cultivated by the organ culture method in an attempt to investigate whether extract of the rat hypothalamus may stimulate the glands directly to release FSH, LH or both. Hypothalamic tissues of mature female rats were extracted with 1.0M acetic acid. FSH-RF or LHRF activity of the extract was determined by estimating FSH or LH activity of cultures treated with the extract. FSH activity was measured by the method of Steelman-Pohley, and LH activity was done by the method of Parlow. The extract could stimulate the release of signifocant amounts of LH, whereas brain cortical extract, oxytocin and lysine-vasopressin were inactive. Contamination of LH in the extract was denied. The results provide evidence for the presence of an LH-RF in the rat hypothalamus. On the other hand, whether there is an FSH-RF in the rat hypothalamus needs to be further investigated. Autoradiography of cultivated glands demonstrated that the hypothalamic extract increased the uptake of 3H-leucine by PAS-positive cells, indicating that the action of the extract is probably related to the synthesis of gonadotropin.

The neural mechanism of the hypothalamus in the regulation of the reproductive function in rats was studied from the view point of the choline acetylase activity in the brain. The cyclic fluctuation in the enzyme activity during the estrous cycle and the marked increase in the activity following castration in the hypothalamus were found. The fluctuation of the enzyme activity was somewhat different between the anterior-and the posterior hypothalamus; the former mainly consisted the cyclic fluctuation of the enzyme activity in the whole hypothalamus during the estrous cycle, and the latter caused the elevation following castration. Sex difference in the pattern of the change of the choline acetylase activity in castrated animals was also observed. The fluctuations in the hypothalamic choline acetylase activity observed in this study would suggest an importance of the role of the cholinergic enzyme system in the by pothalamus in the reproductive function.

Hohlweg found that the administration of large amount of estrogen induces ovulation in immature rats. It is suggested that this ovulation may be evoked by the steroid action in the central nervous system, especially on the hypothalamus. Along with our previous finding the acetylcholine content in the rat hypothalamus fluctuated at 6 to 10 hrs. after the estrogen injection, the similar fluctuations of the choline acetylase and the monoamine oxidase activities were also seen at that time following the administration of estradiol.The results obtained in present studies are quite in keeping with the observation that the activation of hypothalamus for ovulation may occur several hours after the injection of estradiol, the fact indicating the participation of cholinergic and adrenergic mechanisms involved in the hypothalamus in the Hohlweg's phenomenon.

The ultrafine structure of the contact region between the infundibulum and Pars tuberalis of the anterior pituitary was investigated in rats, and following results were obtained.1) Pars tuberalis of the anterior pituitary consists of several layers of relatively small and variously shaped cells with large nuclei and conspicuous cell membrane. They contain neither secretory granules nor vacuoles except sparse mitochondria.2) Around both the capillary loops and the capillaries of the primary plexus of the portal vessels, a wide pericapillary space is always present. Its maximal width measures several micra. Collagen fibrills and numerous extremely fine granules are distributed in this space, and fibroblasts as well as the endfeets of glial processes are also occasionally observed.3) The external layer of the infundibular wall consists of numerous fibres with various calibre range. Most of these fibres are nothing but the processes of the astro lia which contain very few cytoplasmic element. The presence of nerve fibres in this layer was asccrtained. They are arranged verticaliy to the outer limiting surface of the external layer and thus parallel to each other. In addition to the sparse mitochondria, they contain a large number of small vesicles. The vesicles measure about 300-500A in diameter and even the maximal diameter does not exceed 1000A. They resemble “synaptic vesicles”. The fibre which contains neurosecretory granules of high electron density could not be found in the external layer.These characteristic structures of the contact region strongly support the concept that some chemical substance (s) is released from the nerve endings in the external layer of the infundibulum into the capillaries in the median eminence. Although the small vesicles described above, which might be regarded as the morphological representation of this chemical substance, are similar in many respects to the so-called “synaptic vesicles”, the final conclusion on the nature of the small vesicles cannot be derived at present. From the present observation, however, it is very likely that, even if the small vesicles are not identical with the synaptic vesicles, but are of neurosecretory nature, they are somewhat different in character from the ordinary neurosecretory granules contained in the nerve axons of the hypochalamo-neurohypophyseal tractus.

Sirs: Most computed tomographic findings reported in patients with Wernicke's encephalopathy have been those of diffuse cerebral atrophy [1, 9]. Recently, bilateral low density lesions in the thalamic region were reported [5, 6]. This report describes a young boy with Wernicke's encephalopathy in whom serial CT and MRI scans showed a characteristic distribution of lesions with contrast enhancement in the acute phase. A 14-year-old boy had drunk alcohol in gradually increasing amounts since the age of 12 years. He had drunk two to three cups of Japanese "sake" (alcohol content 16%) almost every day, with little food, from early March 1985. On 27 March, 1985, he suddenly developed nausea and vomiting, and became unconscious soon after. Three days later he regained consciousness, but showed markedly unsteady gait, left ptosis and ophthalmoplegia. He was transferred to the Kyushu University Hospital on 25 April , 1985. His nutrition and cardiovascular system were normal. Neurological examination showed that he was slightly confused. He could not calculate and his recent memory was moderately impaired. He had visual hallucinations. No papilloedema was present. The pupils were equal and reactive to light promptly. Upward gaze was limited, moderately on the left and mildly on the right. Abduction of the left eye was moderately impaired. Convergence was impossible. There was no nystagmus. The oculocephalic reflexes were absent in upward directions bilaterally and leftward in the left eye. His speech was slurred. The extremities showed normal power and tone, but moderate incoordination and dysmetria were seen on the right. There was also mild truncal ataxia. The deep tendon reflexes were normal. No pathological reflexes were seen. Sensation was not impaired. The following laboratory findings were normal: renal and liver functions, CSF, blood gas analysis, lactate and pyruvate in blood and CSF. The blood level of thiamine was 57 nmol/ml (normal 30-75). Erythrocyte transketolase activity was decreased to 57.4 mlU/ml haemolysate (normal 70.0-130.5) [4]. After the addition of exogenous thiamine pyrophosphate (TPP), the activity was increased up to 93.8 mlU/ml (TPP effect: 38.7%). Motor conduction velocity in the tibial nerve and sensory conduction velocity in the sural nerve were normal. An E E G showed a background activity of fairly well organized alpha waves with intermittent paroxysms of bilateral theta activity. The unenhanced brain CT scan 8 days after onset was normal, but enhancing lesions were observed bilaterally in hypothalamus, thalamus and in the floor of the fourth ventricle on

• A 53-year-old man with nonfamilial prealbumin-type amyloid polyneuropathy had severe motor, sensory, and autonomic polyneuropathy, beginning at age 48 years. These clinical features closely resembled familial amyloid polyneuropathy (FAP), but abnormal serum prealbumin levels, specific to FAP (Japanese type), were not detected by radioimmunoassay; DNA sequence for prealbumin was normal. Thus, the diagnosis of FAP was excluded. A possible diagnosis of systemic senile amyloidosis was also considered.

The relationship between maternal erythrocyte filterability determined in late pregnancy and infant birth weight was studied in uncomplicated pregnancy. There was a significant positive correlation (r = 0.7671, p less than 0.005). Maternal erythrocyte filterability is suggested to be an indicator of flow state of the placental microcirculation, which affects fetal development.