Role of proteasomes in the formation of neurofilamentous inclusions in spinal motor neurons of aluminum‐treated rabbits

We examined the role of the 20S proteasome in pathologic changes, including abnormal aggregation of phosphorylated neurofilaments, of spinal motor nerve cells from aluminum‐treated rabbits. Immunohistochemistry for the 20S proteasome revealed that many lumbar spinal motor neurons without intracytoplasmic neurofilamentous inclusions or with small inclusions were more intensely stained in aluminum‐treated rabbits than in controls, whereas the immunoreactivity was greatly decreased in some enlarged neurons containing large neurofilamentous inclusions. Proteasome activity in whole spinal cord extracts was significantly increased in aluminum‐treated rabbits compared with controls. Furthermore, Western blot analysis indicated that the 20S proteasome degraded non‐phosphorylated high molecular weight neurofilament (neurofilament‐H) protein in vitro. These results suggest that aluminum does not inhibit 20S proteasome activity, and the 20S proteasome degrades neurofilament‐H protein. We propose that abnormal aggregation of phosphorylated neurofilaments is induced directly by aluminum, and is not induced by the proteasome inhibition in the aluminum‐treated rabbits. Proteasome activation might be involved in intracellular proteolysis, especially in the earlier stages of motor neuron degeneration in aluminum‐treated rabbits.     

Immunohistochemical Detection of Porcine Teschovirus Antigen in the Formalin‐fixed Paraffin‐embedded Specimens from Pigs Experimentally Infected with Porcine Teschovirus

Porcine teschovirus (PTV) antigens were detected by a streptavidin‐biotin complex method in formalin‐fixed paraffin‐embedded tissues of 3‐week‐old pigs that had been inoculated intravenously with PTV Talfan strain. PTV antigens were detected in cytoplasm of nerve cells, glial cells and endothelial cells in the cerebellar nuclei, the grey matter of the midbrain, pons and medulla oblongata and the ventral horn of the spinal cord and of ganglion cells in the spinal ganglion corresponding to those lesions characterized as non‐suppurative encephalomyelitis and ganglionitis. The results of this study suggest that nerve cells of the brain stem and spinal cord and ganglion cells of the spinal ganglion permit PTV replication and represent the main target cell population of PTV. This is the first study to demonstrate PTV antigen by immunohistochemistry in formalin‐fixed paraffin‐embedded tissue specimens from pigs infected with PTV.     

Clinical study of primary carcinoma of the fallopian tube: experience with 14 cases

Between 1950 and 1986, 14 cases of primary carcinoma of the fallopian tube were treated and diagnosed at the Cancer Institute Hospital. These cases constituted 0.13% of the total number of gynecologic malignancies at the hospital during the period. The clinical/pathological findings and prognoses were described. Of the 14 cases, the average age was 56.0 years. The most frequent symptom was atypical genital bleeding, seen in 11 cases (79%). Massive watery discharge was seen in four cases (29%). In preoperative cytologic examination of vaginal smears, six cases (43%) were positive for cancer. All cases underwent operation as therapy. Postoperative irradiation, adjuvant chemotherapy, and/or second-or third- look operation was also used. Histopathologically, all materials were found to be adenocarcinoma. Four cases were well differentiated, seven were moderately differentiated, and three were poorly differentiated. Two patients with stage III and IV cancers died of the disease. Nine patients were still alive at the end of this study. The five-year survival rate was 57% (4/7). In stage I cancers, the five-year survival rate was 80% (4/5). The prognosis of stage I cancer patients was estimated as rather good.     

A Combination of Speckled Lentiginous Nevus with Patch-type Blue Nevus

A peculiar case of “nevus on nevus” was reported. A 67-year-old man had had a pigmented lesion in the left hypochondrial area since birth. The clinicopathologic findings of the pigmented lesion revealed a combination of speckled lentiginous nevus and patch-type blue nevus. This case of “nevus on nevus” is not described under the term of combined nevus as is current in the literature; it was considered to be a subtype of the type II atypical blue nevus described by Kawamura.     

A common FGFR3 mutation functions as a diagnostic marker for achondroplasia-group disorders in the Japanese population

Recent DNA studies performed by several groups have detected mutations of the gene encoding fibroblast growth factor receptor 3 (FGFR3) in patients with achondroplasia-group disorders, including achondroplasia (ACH), hypochondroplasia (HCH), and thanatophoric dysplasia (TD). For this study, we analyzed theFGFR3 gene in 31 Japanese patients with typical ACH, four with HCH, three with a condition intermediate between ACH and HCH (ACH/HCH-intermediate), and one with TD. Of the 31 typical ACH patients, 29 showed a G1138 to A transition and the other two a G1138 to C transversion, both resulting in a common Gly380Arg substitution in the transmembrane domain of FGFR3. The one TD and the four HCH patients did not display any mutations in the transmembrane domain of FGFR3. Of the three ACH/HCH-intermediate cases, one patient showed the Gly380Arg substitution and one did not, and further analysis of the second patient revealed the presence of Asn540Lys substitution. The first patient was, therefore, genotypically diagnosed as ACH and the second as HCH. Peripheral blood leukocyte DNA analysis in the remaining ACH/HCH-intermediate patient indicated an unequal ratio of mutant to normal PCR products, possibly representing a somatic mosaic for the Gly380Arg mutation. Analysis of the common FGFR3 mutation thus appears to help in the molecular diagnosis of patients with achondroplasia-group disorders.     

Differential expression of human beta-defensin 2 in keratinized and non-keratinized oral epithelial lesions; immunohistochemistry and in situ hybridization

Human beta-defensin(hBD)-2, an antimicrobial peptide, is produced by various epithelial cells. Because hBD-2 expression in the oral epithelium has not been assessed, we investigated its localization in normal oral epithelium and epithelial lesions. hBD-2 expression was studied using immunohistochemistry and in situ hybridization on formalin-fixed, paraffin-embedded tissue sections from 30 cases of squamous cell carcinoma and 6 cases of leukoplakia. Immunostaining for hBD-2 was more intense in hyperkeratinized than in ortho- or non-keratinized epithelium. In contrast, signals for hBD-2 mRNA were frequently stronger in non-keratinized epithelium than in hyper- or ortho-keratinized epithelium. The results suggest that keratinization in oral epithelium plays an important role in the biological function of hBD-2 both at the mRNA level and in the retention of the peptide in the epithelium.     

ULTRASTRUCTURE OF AN ANAPLASTIC GIANT-CELL CARCINOMA FOUND 8 YEARS AFTER OPERATION ON A PAPILLARY CARCINOMA OF THE THYROID

Light and electron microscopic studies have been made on an anaplastic giant-cell tumor that developed in a woman 8 years after an operation on the thyroid for papillary carcinoma. Many giant cells were observed in the anaplastic tumor tissue, but no follicles. Numerous tightly-packed mitochondria and abundant ribosomes were present, but there were no desmosomes. The basement membrane was not distinct.     

Inhibitory effect of antiserum to surface antigen P50 of Babesia gibsoni on growth of parasites in severe combined immunodeficiency mice given canine red blood cells

The inhibitory effect of an antiserum to surface protein P50 of Babesia gibsoni on the growth of the parasite was determined with severe combined immunodeficiency mice given canine red blood cells. The antiserum to the recombinant P50 protein significantly inhibited the parasite growth, indicating that P50 might be a useful vaccine candidate.     

Tumor necrosis factor-alpha in the placenta is not elevated in pre-eclamptic patients despite its elevation in peripheral blood

PROBLEM: Tumor necrosis factor-alpha (TNF-alpha) is present in human placental and uterine cells at the early and late stages of gestation and promotes the regulation of trophoblast growth and invasion. We evaluated whether TNF-alpha levels in the placenta and blood of pre-eclamptic women differed from those with normal pregnancies. METHOD OF STUDY: The subjects were 39 pregnant women carrying single fetuses (21 normal-pregnant and 18 pre-eclamptic patients). Their average gestational age at entry was 38-39 weeks. Peripheral blood was collected before the onset of labor and separated serum was stored at -20 degrees C. A tissue segment of the placenta was cut and frozen in liquid nitrogen immediately after delivery at -80 degrees C. The frozen placental tissue was added to phosphate-buffered saline. The tissue was fully homogenized and centrifuged. Separated supernatant was stored at -80 degrees C. TNF-alpha levels in separated serum and TNF-alpha and total protein (TP) levels in separated supernatant were measured. The presence of TNF-alpha in the placenta was evaluated by immunohistochemistry in five pre-eclamptic and five normal-pregnant patients. RESULTS: Serum TNF-alpha levels were higher in pre-eclampsia than in normal pregnancies. However, TNF-alpha/TP levels in the placenta did not differ significantly between the two groups. As for TNF-alpha immunostaining of trophoblastic cells in the placenta, it was weak in three and moderate in two of the normal pregnancies, while it was absent in two, weak in one, and moderate in two in the pre-eclampsia group. CONCLUSIONS: We demonstrated no significant increase in TNF-alpha/TP levels in the placenta in pre-eclampsia despite a significant increase in serum TNF-alpha levels. There was no strong immunostaining for TNF-alpha detected by immunohistochemistry in the pre-eclampsia group. These findings suggest that TNF-alpha in the placenta is not a key cytokine to interfere with normal trophoblast invasion into the myometrium in pre-eclampsia, and that sources other than the placenta may contribute to the elevated levels of TNF-alpha found in the circulation of pre-eclamptic patients.     

Education of medical technologists in North America

The increasing complexity of diseases and advancing medical technologies have recently raised the number of test items and their use. This has caused each department to ask for clinical support by medical technologists, including consultation services on clinical laboratory tests in Japan. Under these circumstances, we think it is necessary to consider a Japanese education system for medical technologists to foster people with advanced ability capable in providing adequate clinical support. It is important that we study medical technologist systems and education systems superior to than ours. Therefore, to investigate the state of the Japanese education system for medical technologists, we conducted a comparison between the medical technologist systems and education systems in foreign countries and those of Japan. The social background in which medical technologists are positioned, their scope of work, and the education systems overseas are different from Japan on many points and we were given many suggestions for what a system in Japan should be like.