Strong growth polarity of yeast prion fiber revealed by single fiber imaging.

Using the yeast prion as a model, we have developed a novel system to observe the growth of individual prion fibers directly. NM fragments, the prion-determining region of the yeast protein Sup35p, were labeled by either red or green fluorescent dyes, and the fiber growth was observed under a fluorescence microscope. When green-Sup35NM was added to the preformed fibers made of red-Sup35NM, 70-97% of green fibers grew unidirectionally, from only one end of individual red fibers, whereas the remainder grew from both ends. Similarly, the majority of red fibers grew from only one end of green fibers when the order of addition was reversed. Sonication of preformed fibers to expose fresh ends did not change the results, excluding a possibility of occasional deformation of one end as the reason of the apparent unidirectional growth. These results indicate the polarity of Sup35 prion fibers and impose constraints on the models of fiber growth.

Dissecting aneurysms at the A1 segment of the anterior cerebral artery--two case reports.

Two rare cases of dissections which involve the anterior cerebral artery (ACA) are reported. A 58-year-old woman presented with a ruptured dissecting aneurysm manifesting as sudden onset of severe headache and consciousness disturbance followed by aphasia, right hemiparesis, paresis of the left lower extremity, and choreoathetotic movements of the upper arms and face. Computed tomography and angiography revealed subarachnoid hemorrhage due to a dissecting aneurysm at the left A1 segment. The dissecting aneurysm was trapped surgically on the day of onset. Her neurological deficits disappeared within a month. A 39-year-old woman experienced continuous dull headache from the day before onset, and then suffered right hemiparesis. Magnetic resonance (MR) imaging revealed cerebral infarction at the left globus pallidus. Angiography and MR imaging revealed a dissecting aneurysm at the left A1 segment and occlusion of the left Heubner's artery. She received conservative treatment and her neurological findings were improved. Dissections or dissecting aneurysms involving the ACA can be classified into three types: Extension of a dissection to the ACA from the internal carotid artery, dissection at the A1 segment, and dissection at the A2-A4 segments. These types of dissection have distinct uniform clinical features.

Retrolabyrinthine presigmoid transpetrosal approach for selective subtemporal amygdalohippocampectomy.

The retrolabyrinthine presigmoid transpetrosal approach is a modification of the subtemporal approach which is suitable for complete amygdalectomy. By drilling away the retrolabyrinthine presigmoid petrosal bone, at least 1 cm more space below and 1 cm more space medially is obtained than in the subtemporal approach, and temporal retraction pressure is diminished when approaching from below. Operative results according to the Engel's classification of seizure control, and pre- and postoperative Wechsler Adult Intelligence Scale (WAIS), revised WAIS, and Wechsler Intelligence Scale for Children scores were measured in 16 patients treated by normal or modified subtemporal amygdalohippocampectomy. Postoperative follow-up ranged from 8 to 79 months. There has been no morbidity or mortality among these 16 patients, and postoperative seizure frequency has been diminished to less than 10% of the preoperative level in 15 of the 16. In eight patients, seizures have been eliminated totally. Subtemporal amygdalohippocampectomy achieved significantly increased performance and full scale intelligence quotient within 2 months after surgery, compared to preoperative levels. Subtemporal amygdalohippocampectomy is an alternative to the transsylvian approach, but is less invasive.

Circulating CD4+CD8+ T lymphocytes in patients with Kawasaki disease.

We serially monitored cell surface antigen expression on mononuclear cells in peripheral blood isolated from patients with Kawasaki disease (KD), and found, for the first time, that a markedly increased number of CD4+CD8+ T lymphocytes was present in some of the patients (11 of the 24 cases). The cases of five of these 11 patients were complicated with coronary artery lesion (CAL); the 13 patients with normal numbers of CD4+CD8+ T lymphocytes did not have CAL. The patients' age, sex and grade of systemic inflammation evaluated by peripheral leucocyte count and serum C-reactive protein levels were not correlated to the number of CD4+CD8+ T lymphocytes. Other cell surface antigen characteristics of the CD4+CD8+ T lymphocytes included CD3+, CD45RA+, CD45RO+, CD16-, and HLA-DR+. These results indicate that the surface antigen characteristics of the KD peripheral blood examined were the same as those of Epstein-Barr virus infection without CD45RA+. These findings provide useful information for the analysis of the pathogenesis of KD.

Generalized metaphyseal modification with cone-shaped epiphyses following long-term administration of 13-cis-retinoic acid.

UNLABELLED: We report on a 6-year-old girl with short stature which developed following the administration of 13-cis-retinoic acid (a synthetic derivative of vitamin A or retinoid) for 40 months as adjunct chemotherapy for neuroblastoma. Radiographic examination suggested osteophyte formation in the cervical spine, which is the most common skeletal manifestation of retinoid toxicity [10, 11]. In addition, severe metaphyseal cupping with a cone-shaped epiphysis primarily affecting rapidly growing long bones was found, which represented impaired enchondral ossification. This epi-metaphyseal alteration, though unusually severe, was reminiscent of the premature epiphyseal closure which has been described as an adverse effect of 13-cis-retinoic acid [10-12]. Other minor skeletal changes included posterior scalloping of the vertebral bodies and increased interpediculate distances, which were related to a widened spinal canal found on CT. A literature search disclosed several primary skeletal dysplasias with superficial radiological similarities to those of the present patient. However, these entities showed significant clinical and radiological differences from our patient. CONCLUSION: The precise cause of the generalized skeletal alteration in the present patient remained unknown, but it conceivably resulted from the administration of 13-cis-retinoic acid.

High levels of circulating interleukin-4 and interleukin-10 in Kawasaki disease.

For analysis of the cytokine network in Kawasaki disease (KD), we measured over time the plasma levels of interferon (IFN)-gamma, interleukin (IL)-4 and IL-10 in patients with KD. Fifteen patients with KD were studied. Eight healthy children were selected as control subjects. Circulating IFN-gamma levels were measured by immunoradiometric assay, and IL-4 and IL-10 levels were measured by enzyme-linked immunosorbent assay. The results were as follows: (1) The plasma levels of IFN-gamma in KD patients in the acute phase were significantly higher than the levels of patients in the convalescent phase (p < 0.05) and those of the control children (p < 0.05). (2) The plasma levels of IL-4 in the KD patients in the acute phase were significantly higher than the levels of the patients in the convalescent phase (p = 0.001) and those of the control children (p = 0.001). (3) The plasma levels of IL-10 in the KD patients in the acute phase were significantly higher than the levels of the patients in the convalescent phase (p < 0.03) and those of the control children (p < 0.005). (4) The investigation of the relationship between the IL-4 and IFN-gamma levels during the acute phase of KD demonstrated a significant reciprocal relationship (p < 0.05). (5) There was no significant relationship between the IL-4 and IL-10 levels during the acute phase. However, plasma IL-10 levels were low in the patients with high levels of plasma IL-4, and the patients with high levels of IL-10 revealed low levels of plasma IL-4. The above results suggested that a variety of patterns of cytokine production was present in the acute phase of this disease, and that the key cytokine, which might regulate the cytokine network, was IL-4.

[Circulating interleukin-4 levels in acute phase Kawasaki disease].

We have measured the plasma levels of IL-4 in patients with Kawasaki disease, serially. The results were as follows: The plasma levels of IL-4 from patients with Kawasaki disease in acute phase (median 17 pg/ml) were significantly higher than those from the patients in convalescent phase (median 1.96 pg/ ml, p = 0.001) or from control children (median 7.64 pg/ml, p = 0.001). These findings imply that Th2 (or Tho) cells may be vigorously stimulated at an acute phase of this disease, and that IL-4 produced by these cells may possibly modulate the pathological conditions of this disease.

[Plasma interleukin-10 levels in Kawasaki disease].

Time course of interleukin-10 (IL-10) in plasma of patients with Kawasaki disease was measured. The results are as follow: (1) IL-10 concentration in plasma of patients in acute phase of Kawasaki disease (median 37.8 pg/ml) was high, compared with that in convalescent phase (5.77 pg/ml) or that of control children (10.2 pg/ml). (2) From the examination of IL-10 concentration in plasma collected by following its time course, it was revealed that most of cases with this disease showed transiently high figure in the acute phase, then the figure diminished promptly afterwards.

Juvenile parkinsonism treated with bilateral pallidotomies--case report.

A 47-year-old female diagnosed as having juvenile parkinsonism at age 38 years developed progressive motor fluctuation while receiving levodopa medication. She underwent right posteroventral pallidotomy which achieved only a transient effect on the wearing-off. An additional procedure on the left pallidum resulted in long-lasting relief of the parkinsonian symptoms.

Malignant nerve sheath tumor of the jugular foramen followed by meningeal dissemination in a patient with neurofibromatosis.

A 20-year-old female with von Recklinghausen's disease became aware of hoarseness and dysphagia with a right neck mass, and received subtotal resection of a jugular foramen neurofibroma. One year later the jugular foramen tumor recurred and pathologic examination at excision showed a malignant transformation. Despite postoperative chemotherapy and radiotherapy, it recurred soon and followed the metastatic cerebral tumor by meningeal dissemination. Malignant nerve sheath tumors of the jugular foramen are very rare and the clinical course and pathological pictures of this tumor are reviewed.

[Intrathecal distribution of ACNU by various modes of its administration analyzed by HPLC and autoradiography].

Various modes of administration of ACNU (nimustine hydrochloride) were tried to make clear which mode is the best method to obtain intrathecal diffuse distribution of ACNU to match the condition of killing of glioma cells (10 micrograms/ml; greater than 30 min.). Tried modes of administration included 1)bolus injection into ventricular cavity, 2)bolus injection into cisterna magna, 3)bolus injection into lumbar subarachnoid space, 4)ventriculo-lumbar perfusion, 5)chiasmatic cistern-lumbar perfusion. Used dose of ACNU was 5 mg/body for all modes of administration. ACNU level in CSF was measured by HPLC method specially developed by authors. To make clear intrathecal distribution of ACNU, autoradiography using 14C-ethylene-ACNU was studied after administration of 10 muCi/Kg of radioactive ACNU. The images were studied by image analyzer system (BAS-2,000 system developed by Fuji Film Co. Ltd). Among the modes of administration tried, ventriculo-lumbar perfusion method gave the best results in terms of lumbar, ventricular, cisterna magna, and basal cistern distribution of ACNU to match the cell kill condition experimentally ascertained. Although, bolus injection of ACNU into cisterna magna gave sufficient amount of ACNU in lumbar region, the initial level of ACNU was too high in cisterna magna, and administration of ACNU once a week for three times in a canine cisterna magna resulted in considerable deterioration of brain stem and basal structure. In addition to it, the level of ACNU in ventricular cavity was not detectable. Lumbar bolus injection resulted in also too much ACNU accumulation at the injected lumbar area, and at the cisterna magna region, ACNU was not detectable.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunological studies on Kawasaki disease: II. Isolation and characterization of an immunosuppressive factor in acute phase sera.

Acute phase serum from a patient with Kawasaki disease possessed strong inhibitory activity for the proliferative response of Con A-stimulated peripheral blood mononuclear cells. The inhibitor was fractionated step-wise by means of DEAE-Sephadex A-50 ion exchange chromatography followed by Sephadex G-100 gel filtration and high performance liquid chromatography. A major protein of 140 kD with 2000 times greater inhibitory activity than the original serum was identified in the final fraction. Immunization of mice with this fraction resulted in the production of three hybridoma clones secreting monoclonal antibodies (MoAb) of IgG1 class which blocked the inhibitory activity of the fraction. Two of these MoAb recognized the same epitope of the inhibitory factor, while the remaining MoAb was directed to a different epitope. Western blot analysis of acute phase sera by the MoAb demonstrated the presence of 140 kD molecules in 43 of 55 patients.

Inhibition of lymphocyte DNA synthesis by plasma from patients with Kawasaki disease.

Plasma obtained from patients with Kawasaki disease during the acute phase markedly inhibited DNA synthesis in autologous peripheral blood lymphocytes (PBLs) stimulated by phytohaemagglutinin-P (PHA-P) or concanavalin A (Con A). The inhibition became less marked with the progression of the disease and there was no effect on DNA synthesis in PBLs stimulated by pokeweed mitogen (PWM). The plasma also inhibited DNA synthesis in PBLs obtained from healthy adults. The postulated suppressors markedly inhibited DNA synthesis in PBLs from healthy adults stimulated by PHA-P, Con A, purified protein derivative (PPD) or mixed lymphocyte culture reaction (MLR) but they had little effect on the DNA synthesis stimulated by PWM or protein A. With respect to the mechanism, the suppression was found to be potentiated by an increase in the concentration of the patients' plasma, and not to be associated with cytotoxicity nor with a deficiency of factor(s) indispensable for PBL proliferation. It was also evident that the suppression was not related to the concentration of the stimulant, to the lengths of the culturing period nor to the presence of prostaglandins.