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We report a 6-year-old girl with anaplastic ependymoma probably originating in the region of the conus medullaris and probably spreading retrogradely to the region of the interventricular foramen (Monro) through the cerebrospinal fluid (CSF). Since ependymoma of the spinal cord rarely occurs in children, and retrograde spreading is extremely rare, the histological features and mechanism of metastasis of the tumor are discussed.

A total of 147 specimens from 93 patients with penile lesions were examined at Nagasaki University Hospital during a 27-year period from 1961 to 1987. The most frequent malignant tumor was squamous cell carcinoma (SCC, 33 cases, 35.5%), followed by extramammary Paget's disease, transitional cell carcinoma, and Bowen's disease. The benign tumors and tumor-like lesions included condyloma acuminatum, cyst of the genitoperineal raphe, and lymphangioma. SCC of the penis accounted for less than 0.1% of all specimens and less than 0.62% of malignant tumors in men filed at our hospital. True phimosis accompanied 81.5% of the SCC cases. The 5- and 10-year survival rates for SCC were 77.2% and 71.3%, respectively. Two patients died of penile SCC. It was considered that an absence of both keratohyaline granules in the granular layer and melanin pigment in the basal layer can serve as a useful histologic indicator for diagnosis of well differentiated SCCs that are otherwise difficult to identify.

A large asymptomatic anterior mediastinal thymolipoma, discovered by chest radiograph during a regular check-up for company employees, was excised from a 33-year-old Japanese man. On immunohistochemical and electron-microscopic examination, clusters of myoglobin-positive cells with cytoplasmic Z band structures were found scattered in the medulla. Myoid cells have been previously seen in the normal thymus as well as in thymic hyperplasia, thymoma, and in the thymus of patients with myasthenia gravis. To our knowledge, this is the first reported instance of myoid cells in a thymolipoma.

Senile changes in the human olfactory bulb were studied histopathologically in 133 individuals ranging in age from 40 to 91 years with a mean age of 64.3 years. Neurofibrillary tangles (NFTs) in the olfactory bulb were observed in 47 subjects aged over 50 years. The frequency of NFTs was 35.3% (47/133) in total and 40.5% (47/116) among subjects 50 years of age or older. The frequency of individuals with NFTs increased linearly with age. Senile plaques (SPs) were observed in 5 individuals over 60 years old at a frequency of 3.8% (5/133) in total and 5.7% (5/88) among individuals 60 years old or more. Granulovacuolar degeneration was rarely seen, and amyloid angiopathy was not recognized. Senile changes in the hippocampus and parahippocampal gyrus were also examined. In some cases, the frequencies of NFTs and SPs in the hippocampal region were not identical to those in the olfactory bulb. However, it was not apparent whether senile changes first appear in the olfactory bulb or in the hippocampal region.

The infectivity of Cryptosporidium muris (strain RN 66), originally isolated from the house rat (Iseki 1986), to various laboratory animals was studied by transmission experiments. After oral inoculation with 1 x 10(6) oocysts, mice, guinea pigs, rabbits, dogs, and cats all discharged endogenously produced oocysts in their feces. Among these host species, mice and cats were highly susceptible to the parasite. The prepatent period for six 3-week-old specific pathogen-free (SPF) mice was 5 days postinoculation (PI), the patent periods varied between 34 and 75 days for each mouse, and the number of oocysts discharged per individual per day (OPD) was 11-46 x 10(6) at the maximum on days 16-26 PI. The total number of oocysts discharged per mouse during the patent period was estimated to be 170-560 x 10(6). Three inoculated cats (1-2 months old) also discharged a large number of oocysts for a long period. Guinea pigs, rabbits, and dogs showed low susceptibility to this strain; the OPD was extremely small and the patent periods were less than 3 weeks. The entire endogenous development of this parasite occurred in the stomach and not in the small and large intestines of these experimental animals. Because of this lack of host specificity, it is suspected that C. muris could be infective to humans, especially immunocompromised patients such as those with AIDS.

A case of pancreatoblastoma, arising in the tail of the pancreas with metastases to the right radius, in an 8-year-old boy is reported. The serum alpha-fetoprotein (AFP) level was over 13 times the normal value before surgery, but returned to normal after removal of the primary tumor. Furthermore, AFP was detected in tumor tissue by immunohistochemistry. This case, representing the second primary non-germ cell pancreatic neoplasm in a child producing elevated serum AFP, supports the use of serum AFP in diagnosing this lesion.

The ultrastructure of Cryptosporidium muris, which parasitizes the stomach of mice, was studied by transmission electron microscopy. The entire development of the parasite occurred in the microvilli of the surface mucus cells in the gastric glands. The ultrastructural features of the attachment site of C. muris to the host cell differed remarkably from those of C. parvum and its closely related species, which parasitize the intestine of various animals. The size of C. muris was greater at almost every developmental stage than that of C. parvum. These findings confirmed that C. muris and C. parvum are distinct species. The mitochondria, subpellicular microtubules, and Golgi complex were demonstrated in detail. A small invagination in the meront and intravacuolar tubules were found in Cryptosporidium. The wall of each developing oocyst in the parasitophorous vacuole was composed of three layers: the outermost layer was considered to be a true oocyst wall, whereas the middle and innermost layers were assumed to develop into the sporocyst wall. The outermost layer was fragile and disintegrated as the oocyst matured. In excystation in vitro, a suture was seen in a thick layer of the two-layered sporocyst wall of an oocyst (sporocyst wall; see Discussion) that enveloped four sporozoites. The fine structure of the attachment site of the present species to the host cell appears to reveal a unique mode of host-parasite interaction in Cryptosporidium infection.

One hundred and fifty-eight cases of mediastinal tumors have been studied clinicopathologically, based on patients of Nagasaki University Hospital from 1961 to 1984. Of these tumors, 29.7% were thymic tumors, 23.4% neurogenic tumors, and 21.5% were germ cell tumors, the frequencies of which reflected the same tendency as other such reports in Japan. Thirty-three cases were malignant tumors. Among them, thymomas were the most common (48.5%) as Wada et al. have reported. Extrathoracic metastases have observed in 2 thymomas. Thymomas associated with myasthenia gravis were seen in 6 cases in which 5 patients are still alive.

The biosynthesis of bicyclomycin by Streptomyces sapporonensis was studied using suspensions of washed mycelium. Nicotinamide and Fe2+ were found to be essential cofactors in the biosynthesis. Production of bicyclomycin was enhanced most effectively in the presence of equal moles of L-leucine and L-isoleucine, which in experiments with radioactively labeled compounds were found to be incorporated into bicyclomycin at equivalent rates. These facts strongly suggest that bicyclomycin biosynthesis involves coupling of equal moles of these two amino acids.

Infants with transient neonatal hypothyroidism, in whom TSH binding inhibitor immunoglobulin G (IgG) (TBII) were sequentially measured, are described. Their mother had been taking thyroid replacement for hypothyroidism due to nongoitrous autoimmune thyroiditis. IgGs inhibiting TSH binding were detected in maternal sera by radioreceptor assay. These IgGs also inhibited the adenylate cyclase response to TSH in human thyroid membranes. Three infants had frank hypothyroidism immediately after birth, and TBII were detected in two of them. In the two surviving infants, hypothyroidism was transient and improved when TBII disappeared from their sera. The profile of TBII in one patient corresponded to the IgG disappearance curve. These findings suggest that the transient neonatal hypothyroidism reported was caused by transplacental transfer of TBII.

Three fluorochromes were applied to stain various parasitic protozoans. By double staining with 4',6-diamidino-2-phenylindole and propidium iodide, differentiation of the nuclei from the cytoplasm can easily be achieved within several seconds. The chromatoid bodies in Entamoeba cysts were stained bright red. Plasmodium yoelii at all stages except late trophozoites and young gametocytes was easily identified. In the oocysts of Cryptosporidium sp., the nuclei and cytoplasm of the sporozoites fluoresced bluish white and red, respectively, whereas the residual body appeared blue or green. The third fluorochrome, Calcofluor white M2R, was suitable for detecting the cysts of Entamoeba spp. and Chilomastix mesnili.

Microscopic examination of cultures of Escherichia coli exposed to bicyclomycin revelaed elongated or spheroplast-like cells. At the lethal level, bicyclomycin was shown to inhibit the synthesis of RNA and protein in the growing cells of E. coli 15 THU, whereas DNA and lipid synthesis were not significantly affected. However, the antibiotic did not block RNA and protein synthesis in vitro. Bicyclomycin was observed to inhibit the synthesis of envelope proteins more markedly than that of cytoplasmic proteins. The synthesis of two major envelope proteins was more sensetive to bicyclomycin than that of the other envelope proteins. One (peak I), which was inhibited to the greatest extent, seemed to be identical with a bound form of lipoprotein, and the other (peak V) with a free form of lipoprotein. Bicyclomycin exhibited inhibitory effects on the exclusive biosynthesis of the lipoprotein in histidine-starved cells of E. coli 15 THU. The biosynthesis of the bound form of lipoprotein was more profoundly inhibited by bicyclomycin than that of the free form. These results indicate that the primary action of bicyclomycin may be due to the interference with the biosynthesis of lipoprotein, and its assembly to peptidoglycan.

Nine children, 1 to 13 years of age, with HBeAg positive chronic hepatitis B received transfer factor (T.F.) monotherapy for 3 to 17 months, and were monitored by check-ups every six months from serum HBeAg, anti-HBe and GPT. In 12 months, 4 subjects became HBeAg negative and had normal serum GPT. In 22 to 48 months, 6 of the nine subjects had negative HBeAg and normal GPT, 2 had positive HBeAg and high GPT values. The remaining 1 subject who was observed for six months after T.F. therapy remained HBeAg positive with a high GPT values. No side effects were observed. These preliminary observations may indicate beneficial effects of T.F. on the natural course of chronic hepatitis B in childhood, though the ultimate effects awaits longer and well controlled clinical trials.

The degeneration of bicyclomycin-producing strains of Streptomyces sapporonensis resulted in sharply depressed bicyclomycin formation in a large scale fermentation. Degenerated strains, whose productivities were only 1/30 to 1/100 of normal strains, could not form aerial mycelia on glucose-BENNETT's agar; they were aerial mycelia negative strains (am-). Repeated transfers of culture, treatment of mycelia with acriflavin, mechanical agitation shock on mycelia or higher growth conditions stimulated the degeneration of producing strains, suggesting the involvement of extrachromosomal elements or plasmids in biosynthesis of bicyclomycin. Shake flask fermentation inoculated with a mixture of a normal high-producing strain and a degenerated low-producing strain resulted in sharply depressed bicyclomycin formation in proportion to the increase of low-producing strain added. It appears that the low-producing strain outgrew the high-producing strain.

The binding of [14C]bicyclomycin to whole cells of E. coli and to the inner membrane proteins was inhibited by dithiothreitol and 2-mercaptoethanol. The reactivity of the drug with the sulfhydryl group was further studied, using methanethiol as a model compound. The kinetics revealed that the reaction was of pseudo-first-order in excess of thiolate anion. Analysis with gas chromatography-mass spectrometry showed that the main product was an adduct of thiol with bicyclomycin in an equal molar ratio. The structure of the adduct was determined by 1H-NMR spectrometry, showing that thiolate attacked the olefinic double bond of the antibiotic. 3'-Acyl derivatives of bicyclomycin did not significantly affect the binding of [14C] bicyclomycin to inner membrane proteins of E. coli. The results suggested that 4,5-double bond hydrocarbons and 3'-hydroxy group of bicyclomycin participate in the binding to E. coli inner membrane proteins, which are presumably the receptors of the antibiotic. The olefinic double bond seems to be the active center of bicyclomycin, reacting with the sulfhydryl group of the receptor protein, although the whole molecular is needed for the activity.