Coexistence of amyotrophic lateral sclerosis and argyrophilic grain disease: A non‐demented autopsy case showing circumscribed temporal atrophy and involvement of the amygdala

We report a case of a 68‐year‐old right‐handed man with sporadic amyotrophic lateral sclerosis (ALS) and argyrophilic grain disease (AGD) having a 22‐month duration. His initial symptoms were dysarthria and swallowing difficulty at the age of 67. Subsequently bulbar palsy and pyramidal signs developed. His cognitive functions including face recognition, personality, and behavior were not changed compared with that of before the disease onset. However, magnetic resonance imaging disclosed severe right side‐predominant temporal atrophy. The neurological diagnosis was bulbar type ALS. Pathological examination disclosed histological evidence of ALS, including loss of Betz cells and lower motor neurons, corticospinal tract degeneration, and Bunina bodies. In addition, severe neuronal loss in the bilateral temporal cortex with an anterior gradient was found. Ubiquitin‐positive inclusions were encountered in the spinal anterior horn cells and hippocampal dentate gyrus, while few ubiquitin‐positive inclusions were noted in the affected temporal cortex. The amygdala, especially the basolateral nuclear group, was severely affected by neuronal loss with tissue rarefaction. Moderate neuronal loss was encountered in the parahippocampal gyrus, and to a lesser degree, in the ambient gyrus. Unexpectedly, many argyrophilic grains, coiled bodies, tau‐positive bush‐like astrocytes, pretangles, and ballooned neurons were found in the limbic system and temporal cortex. In the hippocampus, selective tau accumulation with minor neurofibrillary changes was observed in CA2 neurons. The present case suggests that (i) ALS and AGD do rarely coexist, and (ii) when ALS patients have severe temporal atrophy, not only ALS with dementia but also concurrent AGD should be considered in the differential diagnosis.     

Comparison of p53 expression in proximal and distal gastric cancer: Histopathologic correlation and prognostic significance

Background: The overexpression of p53 has been found to be correlated with prognosis of some carcinomas, including gastric cancer, but no studies have reported on its relationship to the location of gastric cancer. In the present study, we compared the p53 expression of proximal and distal gastric cancer concerning histopathology and prognosis. Methods: A total of 170 tumors in the patients with proximal (80 cases) and distal (90 cases) gastric cancer were studied by immunohistochemical methods. Results: p53 immunopositivity was detected in 28.8% of all tumors. The p53-positive expression in proximal gastric cancer was higher than in distal gastric cancer (38.8% vs. 20.0%, p<0.05). A 5-year survival analysis showed that there is no significant difference between tumors that are p53 positive and p53 negative. No correlation was found between p53 expression and histopathology of gastric cancer. Conclusion: p53 nuclear staining is not useful as a prognostic indicator or as a parameter in gastric cancer.     

Independent association of antibodies against human papillomavirus type 16 and E7 proteins with cervical cancer

The E4 open reading frame (ORF) of human papillomaviruses (HPVs) is transcribed in abundant mRNAs encoding an fusion gene during the productive infection, and the HPV 16 E7 ORF encodes an oncoprotein detectable in the cell lines derived from cervical carcinoma. We examined 421 human sera, which included 108 samples from the patients with cervical carcinoma, for the presence of IgG antibodies against the HPV 16 E4 and E7 proteins by enzyme-linked immunosorbent assay. Bacterially expressed fusion protein lac- and nonfusion protein E7 were purified and used as antigens. All of the 22 serum samples positive for anti-E7 antibody and the 11 out of 15 samples positive for anti- antibody were from the patients with cervical carcinoma, but only one sample was found to contain both anti- and anti-E7 antibodies. These findings show specific and independent association of these antibodies with cervical carcinoma.     

Lacunar skull deformity and hydrocephalus in infants with myelomeningocele: is lacunar skull deformity a predictor of hydrocephalus development?

Objects We evaluated whether the presence of lacunar skull deformity (LSD) with myelomeningocele is a predictive factor for subsequent hydrocephalus development. Materials and methods We reviewed the clinical and radiological records of 18 infants with myelomeningocele, divided the patients into groups with (group A, n=9) and without (group B, n=9) ventriculomegaly at birth and assessed whether the presence of LSD was predictive of the necessity for ventriculoperitoneal shunt (VPS) placement. Results LSD was present in five group A patients. All nine group A patients underwent VPS placement. Among the group B patients, five had LSD; they underwent VPS placement. A significantly higher proportion of those with ventricle enlargement or LSD at birth required VPS placement (p=0.0001). Conclusion Adding to the ventriculomegaly at birth, the presence of LSD alerts to the necessity to monitor these infants closely to determine the necessity for VPS placement.     

Effect of buthionine sulfoximine on orthophenylphenol-induced hepato- and nephrotoxic potential in male rats

A single oral administration of orthophenylphenol (OPP, 1400 mg/kg; about half the LD₅₀) to male Fischer 344 rats produced an elevation of serum transaminase activity 24 h later. Pretreatment with l-buthionine-S,R-sulfoximine (BSO, 900 mg/kg) in the OPP-treated rats potentiated the hepatic and renal damage which was accompanied by necrosis. Six hours after the administration of OPP (700 or 1400 mg/kg), hepatic and renal glutathione (GSH) levels decreased with increasing dosage. Hepatic GSH depletion with OPP was enhanced with BSO pretreatment and the recovery of GSH in both organs was slow in the high-dose OPP group. These results suggest that hepatic and renal damage is associated with a serious and prolonged GSH depletion. When either phenyl-p-benzoquinone (PBQ) or phenylhydroquinone (PHQ), which are intermediates of OPP, was administered orally to rats at 700 or 1400 mg/kg, the mortality with the high dose of PBQ was 75% at 24 h. The serum transaminase activity and UN level increased with the low dose of PBQ, accompanied by necrotic hepatocytes. The toxic effects of PHQ on kidney or liver were less than those on PBQ. These observations suggest that the liver and kidney may be target organs for toxic actions of a large dose of OPP and its intermediate, PBQ.Part of this work was presented at IInd International ISSX Meeting Xenobiotic Metabolism and Disposition, May 16–20, 1988, Kobe, Japan     

Expression of synaptotagmin 1 in the taste buds of rat gustatory papillae

Synapses between taste receptor cells and primary sensory afferent fibers transmit the output signal from taste buds to the central nervous system. The synaptic vesicle cycle at the synapses involves vesicle docking, priming, fusion, endocytosis, and recycling. Many kinds of synaptic vesicle proteins participate in synaptic vesicle cycles. One of these, synaptotagmin 1, binds Ca(2+) phospholipids with high affinity and plays a role in Ca(2+) regulated neurotransmitter release in the central and peripheral nervous systems. However, the expression patterns of synaptotagmin 1 in rat taste tissues have not been determined. We therefore examined the expression patterns of synaptotagmin 1 and several cell specific markers of type II and III cells in rat taste buds. RT-PCR assay showed that synaptotagmin 1 mRNA was expressed in circumvallate papillae. In fungiform, foliate, and circumvallate papillae, the antibody against synaptotagmin 1 yielded the labeling of a subset of taste bud cells and intra- and subgemmal nerve processes. Double labeled experiments showed that synaptotagmin 1 positive cells co-expressed type III cell markers, PGP 9.5, and NCAM. Intragemmal nerve processes positive for synaptotagmin 1 co-expressed PGP 9.5. Conversely, all synaptotagmin 1 expressing cells did not co-expressed type II cell markers, PLCbeta2, or gustducin. These results show that synaptotagmin 1 may play some regulatory roles in vesicle membrane fusion events with the plasma membrane at the synapses of type III cells in rat taste buds.     

Establishment of dental epithelial cell line (HAT-7) and the cell differentiation dependent on Notch signaling pathway

Rat incisors grow continuously throughout life. Producing a variety of dental epithelial cells is performed by stem cells located in the cervical loop of the incisor apex. To study the mechanisms for cell differentiation, we established a dental epithelial cell line (HAT-7) originating from a cervical loop epithelium of a rat incisor. Immunochemical studies showed that HAT-7 produced the cells expressing amelogenin, ameloblastin, or alkaline phosphatase (ALP). To illustrate a role of Notch signaling in the determinant of the cell fate, we examined expression patterns of Notch1 and Jagged1 in HAT-7 density dependently. At lower cell density, Notch1- or Jagged1-expressing cells were not seen. However, when they were fully confluent, cells began to express Notch1 or Jagged1 strongly. Some ALP-positive cells were almost consistent with Notch1-expressing cells but not Jagged1-expressing cells. These results suggested that the determinant of direction of differentiation was associated with Notch signaling pathway.     

T-cell variant of classical Hodgkin's lymphoma with nodal and cutaneous manifestations demonstrated by single-cell polymerase chain reaction

The atypical cells of CD30(+) cutaneous lymphoproliferative disorders (CD30CLD) are commonly of T-cell origin and frequently have a similar morphology as Hodgkin or Reed-Sternberg cells of Hodgkin's lymphoma (HL). HL is one of the tumors associated with CD30CLD. Although most studies support a B-cell derivation of the tumor cells in HL, recently a few cases of classical HL with T-cell genotype have been reported. We report a patient who presented with CD30CLD whose lymph nodes showed classical HL of mixed cellularity subtype at presentation. By single-cell PCR, the same clonal gene rearrangements of the T cell receptor-beta gene locus could be assigned to the CD30(+) and CD15(+) cells of both skin and lymph node. In a lymph node biopsy specimen taken in relapse after several courses of chemotherapy, the CD30(+) tumor cells were abundant. The T cell-derived tumor cells displayed aberrant expression of the Pax-5 gene in all specimens. A common clonal origin of both CD30CLD and HL of the lymph node in the patient presented here suggests that HL with T-cell genotype exists in association with CD30CLD as well as in sporadic cases and may share clonal origin with the skin tumor.     

Estrogen receptor-associated expression of keratinocyte growth factor and its possible role in the inhibition of apoptosis in human breast cancer

Although estrogen is known to play a crucial role in the pathogenesis of breast cancer, the molecular mechanisms underlying the action of estrogen remain elusive. In the present study, we focused on keratinocyte growth factor (KGF) and its receptor (KGFR) in the pathogenesis of breast cancer, as a growth factor mediating estrogen action, since significant roles of KGF were demonstrated in various steroid hormone-dependent tissues. First, using paraffin-embedded specimens from 42 breast cancer patients, we examined expression patterns of KGF and KGFR by both immunohistochemistry using newly generated antibodies and nonradioactive in situ hybridization with T-T dimerized synthetic oligonucleotide probes. We next compared the results with the expression of estrogen receptor (ER) alpha and beta, proliferative activity and apoptotic frequency (TUNEL staining). Also, the similar approaches were taken to analyze the expression and role of KGF in ER-positive (MCF7, ZR-75-1) and ER-negative (SK-BR-3, MDA-MB-231) human breast cancer cell lines in vitro. In the surgical specimens, KGF was expressed in cancer cells as well as stromal cells in 19/42 cases (45%), while KGFR was found in cancer cells in 24/42 cases (57%). The distribution of protein and mRNA in the analysis of both KGF and KGFR expression generally coincided. Moreover, KGF expression was closely associated with the expression of ER alpha, and the coexpression of KGF and KGFR significantly correlated with lower TUNEL index, but not with proliferative activity. In accordance with the in vivo findings, KGF expression was detected only in ER alpha-positive MCF7 and ZR-75-1 cells in vitro. And more importantly, we found the inhibitory effect of KGF upon the induction of apoptosis by anticancer drugs in MCF7 cells. Collectively, our results indicate that ER alpha may be involved in KGF expression, and that KGF may play antiapoptotic roles, rather than mitogenic, in human breast cancer.