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A 27-year-old woman was admitted to Nagasaki University Hospital complaining of abdominal pain and fever. Percutaneous transhepatic cholangiography showed multiple cystic dilatations of the intrahepatic bile ducts without stone formation. The illness was diagnosed as a pure type of Caroli's disease. No surgical intervention was made. Subsequently, the patient suffered repeated attacks of cholangitis, and six years later, computed tomography demonstrated cystic lesions of both lobes of the liver and stones within the cystic lesions of the right lobe. We collected 62 cases of Caroli's disease reported in the Japanese literature, including our own case. Among them, cholangitis was found in 43.5%, hepatolithiasis in 30.6%, esophageal varices in 17.7% and cholangiocarcinoma in 8.1%. It is difficult to successfully treat Caroli's disease involving both lobes of the liver. Long-term repeated cholangitis could lead to fibrosis of the liver, hepatolithiasis, portal hypertension and cholangiocarcinoma. Considering the above-mentioned aspects of the disease, careful follow-up studies are required in each case.

Kuru plaques are the pathologic hallmark in Gerstmann-Sträussler syndrome (GSS). To demonstrate that prion protein (PrP) is a component of kuru plaque cores, we fractionated and sequenced kuru plaque core derived peptides, following digestion with Achromobacter lyticus protease I. We identified 3 PrP-derived peptides by reverse-phase high-performance liquid chromatography and found a fragment of digests derived from a missense variant of PrP. The variant PrP was also present in the prion rod fraction in patients with GSS. This substitution may play a major role in cerebral amyloidogenesis.

We report the clinical progression of the Gerstmann-Sträussler-Scheinker disease (GSS) in a family of Alsatian origin. The age of onset and duration of evolution were variable. The clinical picture became more complex over the generations: isolated dementia in the first generations, then, more recently, a triad of pyramidal, pseudobulbar syndrome and dementia associated with symptoms indicating spread of damage to the spinal cord and cerebellum. Study of the prion gene showed that in all patients analyzed and in 10 healthy family members, there is a double mutation of codon 117 leading to loss of the restriction site PvuII and to the replacement of an alanine by a valine. We did not find the mutation of codon 102 reported in 5 GSS families. The role of these mutations in the pathogenesis of the disease is unclear: marker for a particular susceptibility to the encephalopathies due to the prion, or direct role in the disease? Further study of the family, particularly the healthy carriers, could suggest the answer. GSS seems to be an especially useful model for the study of the role of a foreign abnormal protein in the synthesis and regulation of host proteins.

Using immunostaining with anti-prion protein (PrP) antiserum, we detected numerous kuru plaques in the brain of a 24-year-old man with Gerstmann-Sträussler-Scheinker syndrome. Immunoreactivity on Western blotting of the protease-resistant PrP fraction from the frozen brain was weak. PrP gene analysis showed substitution of alanine to valine in codon 117 but no substitution in codon 102. As the experimental transmission of the disease to mice was negative, a pathogen of a relatively low infectivity may cause the disease in predisposed family members.

Amyloid beta-protein (BP) deposited in Alzheimer brains is a cleavage product of a larger precursor (BPP). The BPP gene encodes three types of mRNA generated by alternative splicing, two of which contain the sequence encoding Kunitz-type serine-protease inhibitor (serpin). To investigate the regulatory mechanisms of BPP synthesis at the gene level, we isolated 36 genomic DNA clones covering all the exons of the human BPP gene. This gene consists of 18 exons and spans more than 170 kb. BP is encoded by the 16th and the 17th exons and the serpin domain by the 7th exon. Sequence analysis showed that the 7th and 8th introns lack a typical branchpoint for splicing. This might relate to the alternative splicing. The promoter of the BPP gene has some characteristics of those of housekeeping genes and contains a number of possible methylation sites. The methylation status of the promoter was analyzed by Southern blotting but no alteration was observed among tissues and between control and Alzheimer brains. We also tested the roles of two possible activator protein-1-binding sites and a possible heat-shock element found within the promoter. Northern blotting showed that the transcription of the BPP gene was apparently induced by 12-O-tetradecanoylphorbol-13-acetate (phorbol derivative) in HeLa cells.

Congophilic kuru plaques, one of the pathological hallmarks in kuru and Gerstmann-Sträussler syndrome, are sometimes present in patients with Creutzfeldt-Jakob disease (CJD). The congophilic kuru plaques are composed partly of a host-encoded prion protein, and a missense variant prion protein with the codon 102 proline-to-leucine change (Leu102) is commonly present in patients with Gerstmann-Sträussler syndrome. To investigate the relationship between this syndrome and CJD with congophilic kuru plaques, we made a sequence analysis of the prion protein gene from patients with CJD, with or without congophilic kuru plaques. We found no alterations other than the Leu102 change, common to Gerstmann-Sträussler syndrome, in one of the prion protein alleles of the patient with congophilic kuru plaques. In the prion protein genotype analysis of other patients with CJD, the Leu102 allele was revealed to be carried heterozygously by 6 of 7 patients who had CJD with congophilic kuru plaques, yet no patient with CJD without congophilic kuru plaques had this allele. Interestingly, the Leu102 allele was also carried by some unaffected relatives of 3 patients with CJD with congophilic kuru plaques but with no apparent familial occurrence of a similar neurological disorder. Our findings show that CJD with congophilic kuru plaques should be categorized as belonging to Gerstmann-Sträussler syndrome, not CJD, and also suggest that the variant prion protein with Leu102 is closely related to the amyloidogenesis seen in subjects with congophilic kuru plaques.

To elucidate 1-carnitine chloride effects ischemic myocardium for the possibility of a salvage of risk zone around necrosis in myocardial infarcts of dogs, a quantitative evaluation of the extent of myocardial infarcts was done by size detection with use of monastral blue and tissue dehydrogenase histochemistry at 20 hours after coronary ligation. The results show that the ratio of unsalvaged infarct zone to occluded coronary bed is 85.3 +/- 2.9% in the control group, while it is 53.2 +/- 3.6% in the 1-carnitine administered (1 C) group. The difference between these ratios is statistically significant (p less than 0.01). The results also indicate significantly lower serum CPK concentration. Therefore, carnitine may play a role in preventing a size extention of infarcts through improving an altered lipid metabolism, particularly a fatty acid metabolism, of myocardial cells in the risk zone.

Reports of 35 long-term more than five years survivors after resectional surgery which was performed for carcinoma of the pancreas from 1966 to 1980 were collected from major institutions in Japan and analyzed. Male to female ratio was 0.94:1 and average age was 56 years old. In 34 of the 35, the tumor was located at the head of the pancreas, 32 received pancreatoduodenectomy and two underwent total pancreatectomy. One patient with carcinoma of the tail received distal pancreatectomy. There was no correlation between the size of tumor and the postoperative prognosis. It seems that lymph node metastasis is not an obstacle to long postoperative survivals when they are removed, and also invasion to the pancreatic capsule shows no relationship to prognosis. However, there were no definite or severe invasions to the retroperitoneal tissue, nor to the portal venous system in the 35 patients at all. It is considered that invasion to the retroperitoneal tissues and to the portal venous system may be the most influential factor to the postoperative prognosis.

The host-encoded prion protein (PrP) is a component of transmissible amyloid deposited in the brains affected by Gerstmann-Sträussler syndrome (GSS). Recently GSS in two unrelated Caucasian families has been reported to be linked to an amino acid change in PrP codon 102, proline to leucine (Leu102). However, it has not been clear whether the change is commonly found to GSS regardless of ethnic origin. We report here that Leu102 is also found in all the Japanese GSS patients tested. Interestingly, one French GSS patient was found to have another change, alanine to valine in codon 117 (Val117), instead of Leu102. Our results indicate that Leu102 is closely related to GSS irrespective of ethnic origin, but not the sole mutation related to GSS. Val117 may also be related to GSS.

The application of the stroboscopic scanning electron microscope to gigahertz Gunn effect devices is discussed. Two modes of operation, the deflection mode and the bunching mode, are considered. In the bunching mode, using 1.5 ps beam pulses, two-dimensional voltage contrast in a Gunn effect device triggered at 1 GHz has been observed. A powerful technique for a device in pulsed operation is also presented. With this technique, the nonuniform domain propagation in the three-dimensional-structure Gunn device in pulsed operation has been clearly observed. The duty cycle of the pulsed operation has been 4x10(-3).

A male patient with an arterio-portal fistula resulting from a mesenteric arteriovenous malformation, who developed portal hypertension and liver cirrhosis, is presented herein. The malformation was considered to be congenital in origin and its location made any ablative surgical procedure impossible. Such alternative treatments as ligation of the afferent arteries, followed by transarterial embolization were therefore given, but both were unsuccessful. We also present a review of the literatures of mesenteric arteriovenous fistula. Radical surgical approach for this rare entity is proposed. The case reported here as related to mesenteric arteriovenous communications of congenital origin is the seventh such case published, and the first which was ever found to be located in the trunk of the superior mesenteric artery.

Kuru plaque is a pathognomonic feature in the brain of patients with Creutzfeldt-Jakob disease (CJD) and in the brain of CJD-infected mice. Kuru plaques from CJD-infected mice were immunolabeled with rabbit anti-murine prion protein (PrP) absorbed with human PrP, but not so with mouse anti-human PrP. Therefore, the murine kuru plaque is composed of the host (mouse) PrP and can be distinguished antigenically from human PrP. Immunostaining using the anti-murine PrP and formic acid enhancement on tissue sections revealed not only birefringent kuru plaques but also nonbirefringent diffuse and small PrP accumulations. This immunohistochemical detection of kuru plaques provides more positive evidence than heretofore employed histochemical approaches. There were kuru plaques in brains of the first passage mice inoculated with tissues from 30 (91%) of 33 patients with CJD, the 3 negative patients belonging to a type of Gerstmann-Sträussler syndrome. Tissues from 6 other demented patients did not produce kuru plaques. In the evaluation of spongiform changes, mice inoculated with tissues from 23 (70%) of 33 patients were considered cases of successful transmission. In some mice, kuru plaques were present in the absence of spongiform changes. Further inoculations from 9 mice with kuru plaques but no spongiform changes were successful in almost all mice. Therefore, mice with murine kuru plaques in the absence of spongiform changes are also infectious. Thus, the presence of murine-specific kuru plaques can serve as another hallmark of a successful transmission.

The generation and measurement of subpicosecond electron beam pulses by the transverse-longitudinal combination gate system is described. The temporal property of the pulse gate is analyzed with the help of the longitudinal emittance diagram. Close agreement has been obtained between the calculated pulse width and the observed one which was measured by the Lissajous's figure method. A beam pulse of 0.2 ps (FWHM) was produced.

We presented a case of 6 episodes of the right painful oculomotor nerve palsy for 10 years, accompanied by a posterior ethmoidal mucocele on the same side. No destructive bone lesions were shown on every recurrence with the brain CT. For the pathogenesis of neurological involvement in cases of mucocele, either the direct compression by an expanding mucocele or the inflammatory infiltration from a mucocele has been considered. In this case the latter mechanism is considered to be responsible for the etiology of the painful oculomotor nerve palsy. Cases of the painful oculomotor nerve palsy with paranasal lesion or history of parasinusitis are characterized by (1) predominant in male, (2) neurological manifestations unilaterally on the same side of paranasal lesion, and (3) frequent recurrence of neurological symptoms.

Experimental myocardial infarction was produced in 15 subject swine using a balloon catheter to occlude the left anterior descending coronary artery (LAD). After 30 minutes obstruction, the LAD was reperfused, and then the animals were sacrificed at 3 hours, 6 hours, 24 hours, and 48 hours after the onset of coronary occlusion, respectively. During and after the experiment they were investigated physiologically and pathomorphologically to measure the size of myocardial infarct, and the obtained results are as follows; Experimentally produced myocardial infarcts could be detected histopathologically by routine gross and light-microscopical means in the group which had suffered from ischemia for over 24 hours till sacrifice. Ischemic areas could not be distinguished from normal areas of the myocardium by routine techniques, but could be identified enzyme-histochemically in the groups observed for less than 6 hours. The mean weight ratio of infarcted myocardium to total ventricular myocardium was 25 +/- 3.6%. This method was useful for measuring infarct size.