Genome types of adenovirus types 19 and 37 isolated from patients with conjunctivitis in Hiroshima City

A total of 74 strains out of 33 strains of adenovirus type 19 (Ad19) plus 103 strains of type 37 (Ad37) isolated from patients with conjunctivitis at two ophthalmology clinics in Hiroshima City during the period March 1983 to December 1986 were analyzed by eight DNA restriction endonucleases in comparison with their prototype strains. All 27 Ad19 isolates examined displayed identical DNA cleavage patterns with all enzymes used (HindIII, KpnI, PstI, XhoI, BamHI, SacI, EcoRI, and SmaI), but their cleavage patterns were different from those of the prototype except with HindIII. The genome type of these isolates was tentatively named Ad19a. Forty-seven Ad37 isolates examined were divided into three genome types. They were tentatively named Ad37p, Ad37a, and Ad37b: 16 isolates (Ad37p) displayed DNA cleavage patterns identical with those of the prototype with all eight enzymes described above. Thirty isolates (Ad37a) showed the same patterns as the prototype except with EcoRI. One isolate (Ad37b) showed the same patterns as the prototype except with SmaI. The most frequently isolated genome type during the period studied was Ad37a, but the change of the predominant genome type in yearly incidences was observed.     

Effect of solvent evaporation rate on microphase-separated structure of segmented poly(urethane-urea) prepared by solution casting

A useful instrument for polymer film preparation by solution casting was employed in this study. It enabled us to control the solvent evaporation rate of the polymer solution. By using this instrument, the aggregation of hard segments in segmented poly(urethane-urea) (SPUU) was investigated. SPUU was prepared from poly(tetramethy1ene oxide), 4,4′-diphenylmethane diisocyanate and ethylenediamine. The effect of solvent evaporation rate on the microphase-separated structure of SPUU was elucidated by dynamic mechanical analysis, tensile test, differential scanning calorimetry analysis, small-angle X-ray scattering measurement, IR and IR dichroism analyses. The aggregation of hard segments in SPUU was observed to be affected considerably by the solvent evaporation rate of the cast film during the preparation. It was found that the slower the solvent evaporation rate, the higher the aggregation of hard segments to form rigid hard segment domains in SPUU. Nine months after casting, this casting effect still remained on the aggregation state of hard segments of SPUU films, although the interdomain spacing was not influenced by its rate.     

Ascending and descending internuclear connections of the trigeminal sensory nuclei in the cat. A study with the retrograde and anterograde horseradish peroxidase technique

The distribution of cells of origin of ascending and descending internuclear connections in the trigeminal sensory nuclei was studied by the retrograde horseradish peroxidase technique in the cat. The termination of collaterals of these ascending axons was also studied by the anterograde transport of horseradish peroxidase. Following injections of horseradish peroxidase into the ventral part of the principal sensory nucleus and the adjacent reticular formation many small neurons were labeled ipsilaterally in the whole area of the caudal portion of the nucleus interpolaris and in laminae III and IV of the nucleus caudalis. Labeled neurons were also found in laminae I and V. Injections limited to either nucleus oralis, the ventral part of the principal sensory nucleus and the medial parabrachial nucleus labeled similar types of neurons in the above regions with a topographic relationship; neurons in the dorsal part of the nuclei caudalis and interpolaris project, dorsally, to rostral portions of the trigeminal sensory nuclei while those in the ventral part of the nuclei caudalis and interpolaris project ventrally. Anterograde labeling of axons arising from the nucleus caudalis demonstrates that the axons ascend in the intranuclear bundles and the adjacent reticular formation, and give off collaterals to the nuclei interpolaris and oralis, and the ventral part of the principal sensory nucleus. Injections limited to the nucleus caudalis labeled small neurons in the rostral portion of the nucleus oralis and the caudal portion of the nucleus interpolaris. The present study suggests that these ascending and descending internuclear connections of the trigeminal sensory nuclei may modulate transmission of afferent inputs to various projection sites, such as thalamus, superior colliculus, cerebellum and spinal cord.     

Accumulation of filamentous tau in the cerebral cortex of human tau R406W transgenic mice

Missense mutations of the tau gene cause autosomal dominant frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), an illness characterized by progressive personality changes, dementia, and parkinsonism. There is prominent frontotemporal lobe atrophy of the brain accompanied by abundant tau accumulation with neurofibrillary tangles and neuronal cell loss. Using a hamster prion protein gene expression vector, we generated several independent lines of transgenic (Tg) mice expressing the longest form of the human four-repeat tau with the R406W mutation associated with FTDP-17. The TgTauR406W 21807 line showed tau accumulation beginning in the hippocampus and amygdala at 6 months of age, which subsequently spread to the cortices and subcortical areas. The accumulated tau was phosphorylated, ubiquitinated, conformationally changed, argyrophilic, and sarcosyl-insoluble. Activation of GSK-3beta and astrocytic induction of mouse tau were observed. Astrogliosis and microgliosis correlated with prominent tau accumulation. Electron microscopic examination revealed the presence of straight filaments. Behavioral tests showed motor disturbances and progressive acquired memory loss between 10 to 12 months of age. These findings suggested that TgTauR406W mice would be a useful model in the study of frontotemporal dementia and other tauopathies such as Alzheimer's disease (AD).     

Histopathological characterization of aortic intimal sarcoma with multiple tumor emboli

A case of aortic intimal sarcoma with multiple tumor emboli and distal metastasis is reported. All metastasis (adrenal, spleen) were via the arteries. This case also had independent lung cancer. Macroscopically, the aortic tumor did not form a bulged mass, but had linear ulceration with abundant mural thrombi. Poorly cohesive large atypical cells were seen in the intima of the abdominal aorta without invasion into the media. Tumor cells were disseminated into the mural thrombi on the aorta and embolized its branches. In the metastatic tumor or tumor emboli of the distal artery, there were not only large atypical cells, but also the foci of spindle-shaped cells or epithelioid differentiation. Tumor cells in the aorta were immunohistochemically positive for only vimentin. Muscle-specific actin was positive focally for spindle-shaped cells of tumor emboli and metastatic tumors. Furthermore, cytokeratin-positive cells were scatteredly seen. All tumor cells were negative for factor VIII and did not have a histologic or phenotypic analogy with lung cancer. The primary intimal sarcoma in the present case was of undifferentiated non-endothelial intimal stromal cell origin, and may have had multipotential for differentiation. Investigation of the metastatic site was useful for recognizing the features of this tumor.     

Virulence of Streptococcus mutans: comparison of the effects of a coupling sugar and sucrose on certain metabolic activities and cariogenicity.

A coupling sugar preparation (sucrose-free [CSSF]), which contains a mixture of sugars, oligosaccharides, and oligosaccharides terminated at the reducing end by sucrose, served as a substrate for growth and acid production by Streptococcus mutans 6715. However, CSSF was a poor substrate for cellular aggregation, glucosyltransferase activity, plaque formation, and adherence of cells to glass surfaces. In the presence of sucrose, CSSF inhibited glucosyltransfer activity and adherence of cells. The substitution of CSSF for sucrose in a rat diet significantly reduced caries score. Furthermore, rats fed diets containing sucrose and CSSF had significantly fewer carious lesions than did rats fed a sucrose diet.     

Cats are protected against feline immunodeficiency virus infection following vaccination with a homologous AP-1 binding site-deleted mutant

Summary.  Following establishment, via the vaginal route, of infection with an AP-1 binding-site deleted mutant (ΔAP-1) of feline immunodeficiency virus (FIV), cats were challenged with a homologous intact strain (TM2) of FIV. The cats were observed for 23 weeks to evaluate the efficacy of the ΔAP-1 against the homologous TM2 strain challenge. These two viruses were differentiated by Southern blotting after amplification of proviral DNA by semi-nested polymerase chain reaction in DNAs of peripheral blood mononuclear cells and tissues. A TM2-specific band was detected in one cat exposed to but not infected with ΔAP-1, but not in two ΔAP-1-infected. These results indicate that ΔAP-1 could protect against subsequent challenge with homologous FIV TM2 strain. Received December 23, 1998 Accepted March 31, 1998     

Heterotopic transplantation of the failing rat heart as a model of left ventricular mechanical unloading toward recovery

The left ventricular assist device (LVAD) is usually used in patients with end-stage heart failure as a bridge to transplantation. Recently, some studies have reported functional recovery with the use of an LVAD, although the mechanisms responsible for recovery are not fully understood. We investigated the functional recovery of the infarcted, failing rat heart in response to mechanical unloading after heterotopic transplantation. Heart failure was induced in Lewis rats by ligating the left anterior descending artery. After 4 weeks, the infarcted hearts were harvested and heterotopically transplanted. The transplanted infarcted heart was removed after 2 weeks of unloading and examined for hypertrophy and fibrosis, as well as for mRNA levels encoding for brain natriuretic peptide, sarco(endo)plasmic reticulum Ca(2+)-ATPase2a (SERCA2a), and beta1- and beta2-adrenergic receptors. Normal and infarcted rats without transplantation served as control animals. The infarcted heart was hypertrophied as evidenced by an increase in heart weight and myocyte diameter. After unloading the infarcted heart for 2 weeks, there was a decrease in heart weight and myocyte diameter. However, the percentage of myocardial fibrosis increased after unloading. The mRNA expression of brain natriuretic peptide and the beta2-adrenergic receptor significantly improved after mechanical unloading. The levels of SERCA2a mRNA tended to increase after unloading. In conclusion, unloading the failing, infarcted heart can help normalize left ventricular hypertrophy and cardiac gene expression. This unloading model appears to partially mimic the conditions of hemodynamic support with an LVAD in heart failure patients and potentially offers insights into the mechanisms of functional recovery.     

A pedigree analysis with minimised ascertainment bias shows anticipation in Met30-transthyretin related familial amyloid polyneuropathy.

In type I familial amyloid polyneuropathy (FAP) caused by a variant Met30-transthyretin (TTR), genetic anticipation has been reported. To determine whether anticipation of the disease is a true biological phenomenon or the result of ascertainment bias, we compared age at onset of the affected child with that of the affected parent in 68 parent-child pairs (including data on assumed age at onset and on asymptomatic obligate heterozygotes and parents at obligate 50% risk) in 15 families. Excluding the parent-child pairs involving the proband and "bilineal pairs", onset occurred earlier in the child than in the transmitting parent in 60 out of 68 "unilineal pairs". After correction for ascertainment bias resulting from incomplete penetrance and reduced biological fitness in early onset patients, the number of anticipation pairs (60 pairs) was still significantly larger than that of non-anticipation pairs (29.7 pairs) (p < 0.05). When the children were sons, the difference in age at onset was significantly greater in the mother-son pairs than in the father-son pairs (p = 0.023). Although not all ascertainment biases could be eliminated, these data show strong evidence that anticipation in the transmission of Met30-TTR FAP is a true biological phenomenon.     

Expression of lysosome-associated membrane proteins in human colorectal neoplasms and inflammatory diseases

The lysosome-associated membrane proteins (LAMPs)-1 and -2 are major constituents of the lysosomal membrane. These molecules are known to be among the most glycosylated proteins of several types of cells and cancer cells, and their expression in cancer cells is marked by a distinct difference in the structures of the oligosaccharides as compared to nonmalignant cells. We analyzed by immunohistochemistry the intensity and distribution of LAMP-1 and LAMP-2 in 9 human colorectal cancer cases and in 16 control cases, including inflammatory diseases (diverticulitis, ulcerative colitis, and Crohn's disease). LAMP proteins were expressed more intensely in the epithelium of colorectal neoplasms than in normal mucosa (P < 0.05), and no significant differences were found between adenoma and cancer cells (P > 0.05) in the same tissue section. Further, in sites of inactive inflammatory diseases and nonneoplastic areas in cancer specimens, no significant increases in epithelial LAMP proteins were observed, even in the proliferative zone of the lower crypt epithelium. Northern blot analysis showed increased expression of LAMP-1 and LAMP-2A in two of three colorectal cancers examined and increased LAMP-2B in all three cancers. Our findings suggest that LAMPs are related to neoplastic progression, but there is no direct association between the expression of LAMP molecules and cell proliferation.