Somatotopic termination of the spino-olivary fibers in the cat,studied with the wheat germ agglutinin-horseradish peroxidase technique

Summary Terminal sites of the spino-olivary fibers (SOFs) were examined by the anterograde transport of wheat germ agglutinin-horseradish peroxidase in the cat. The tracer was injected at various spinal cord levels from the first cervical to the caudal segments. The SOFs derived from the C1-T1 segments terminated medially in the caudal half (levels II–VIII of Brodal) of the medial accessory olive (MAO), which projects to the A zone of the cerebellar cortex, whereas the SOFs derived from the L6-S1 segments terminated laterally in the caudal half (levels I–VIII) of the MAO. No projections were found from the T2-L5 segments to the MAO. In the dorsal accessory olive (DAO), the SOFs terminated at levels III–XIV; the DAO projects to the B zone and the C1 and C3 zones of the cerebellar cortex. The SOFs derived from the C1-C4 segments terminated in the most medial part of the DAO (levels III–XIV), followed laterally by those from the C5-T1 segments. Further laterally, the SOFs derived from the T2-L5 and the L6-S1 segments terminated in the mediolateral order at levels V–XIV. The SOFs from the L6-S1 segments occupied the most lateral part of the DAO. The present study demonstrates that there is a distinct somatotopic termination of the SOFs in the mediolateral order in the caudal MAO and the DAO.     

Five-year follow-up study of mother-to-child transmission of Helicobacter pylori infection detected by a random amplified polymorphic DNA fingerprinting method

Recent studies have speculated on the possible role of the mother in transmitting Helicobacter pylori infection to their children. In an attempt to either prove or disprove this supposition, we investigated the rates of infection of children born to H. pylori-positive mothers from birth to 5 years of age using serology and the stool antigen test. When infection of the children did occur, the strains from the children were compared to those of their mothers using DNA analysis. Sixty-nine of the 350 pregnant mothers (19.7%) had a positive serology for H. pylori. Fifty-one children underwent serological examinations and stool antigen tests at 4 to 6 days after birth, followed by 1, 3, and 6 months. They were continuously given the stool antigen test at 4- to 6-month intervals until the age of 5 years. Gastric juice samples were collected from the infected children and their mothers for culture and DNA analyses using a random amplified polymorphic DNA fingerprinting method. None of the 51 children acquired H. pylori infection during the first year of life. Of the 44 children enrolled in a 5-year follow-up study, five (11%) acquired H. pylori infection. They acquired the infection at the age of 1 year 2 months, 1 year 3 months, 1 year 6 months, 1 year 8 months, and 4 years 4 months. Random amplified polymorphic DNA fingerprinting confirmed that the strains of the five children exhibited DNA fingerprinting patterns identical to those of their mothers. These findings suggest that mother-to-child transmission is the most probable cause of intrafamilial spread of H. pylori.     

Immunopathological activities of extracellular products of Streptococcus mitis, particularly a superantigenic fraction.

Previously, we prepared extracellular products, fractions F-1 and F-2 of Streptococcus mitis 108, an isolate from the tooth surface of an infant, and showed that F-1 exhibited inflammatory cytokine-inducing activities. In the present study, we present evidence that fraction F-2 induced human T-cell proliferation in the presence of irradiated human peripheral blood mononuclear cells and selectively activated T cells bearing V beta 2 and V beta 5.1 in the T-cell receptor. F-1, on the other hand, stimulated human gingival fibroblasts to support the T-cell proliferation in the same way as human gamma interferon or Prevotella intermedia lipopolysaccharide (LPS). Fraction F-1 also primed gingival fibroblasts to support the production of interleukin-2 and gamma interferon by the T cells upon stimulation with F-2. Human gingival fibroblasts stimulated with fraction F-1, like those stimulated by P. intermedia LPS and human gamma interferon, exhibited human leukocyte antigen (HLA)-DR mRNA expression and cell surface HLA-DR molecules as detected by enzyme-linked immunosorbent assay. An anti-HLA-DR monoclonal antibody inhibited T-cell proliferation in response to F-2, probably through inactivating the accessory function of HLA-DR-bearing fibroblasts. T cells activated with F-2 in the presence of irradiated peripheral blood mononuclear cells exhibited definite cytotoxic effects against fibroblasts and squamous carcinoma cells originating from human oral tissues. These findings are strongly suggestive of an association of extracellular products of viridans streptococci with pathogenesis of oral mucosal diseases, particularly those disorders in gingiva which are accompanied by heavy infiltration of T cells.     

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.     

Graphic and movie illustrations of human prenatal development and their application to embryological education based on the human embryo specimens in the Kyoto collection.

Morphogenesis in the developing embryo takes place in three dimensions, and in addition, the dimension of time is another important factor in development. Therefore, the presentation of sequential morphological changes occurring in the embryo (4D visualization) is essential for understanding the complex morphogenetic events and the underlying mechanisms. Until recently, 3D visualization of embryonic structures was possible only by reconstruction from serial histological sections, which was tedious and time-consuming. During the past two decades, 3D imaging techniques have made significant advances thanks to the progress in imaging and computer technologies, computer graphics, and other related techniques. Such novel tools have enabled precise visualization of the 3D topology of embryonic structures and to demonstrate spatiotemporal 4D sequences of organogenesis. Here, we describe a project in which staged human embryos are imaged by the magnetic resonance (MR) microscope, and 3D images of embryos and their organs at each developmental stage were reconstructed based on the MR data, with the aid of computer graphics techniques. On the basis of the 3D models of staged human embryos, we constructed a data set of 3D images of human embryos and made movies to illustrate the sequential process of human morphogenesis. Furthermore, a computer-based self-learning program of human embryology is being developed for educational purposes, using the photographs, histological sections, MR images, and 3D models of staged human embryos.     

PCR analysis of the Y chromosome long arm in azoospermic patients: evidence for a second locus required for spermatogenesis

We analyzed DNA from 63 Japanese men with either azoospermiaor severe oligospermia whose Y chromosomes were cytogeneticallynormal. A total of 16 loci were examined: 15 loci on the longarm between DYS7E and DYZ1, and the YRRM1 locus, a candidategene for the azoospermic factor, AZF. One patient with a perlcentricinversion of the Y chromosome was also included. We detectedmicro-deletions in ten individuals. The YRRM1 gene was Involvedin only three of them. The remaining seven patients showed deletionbetween DYS7C and DYS239 in common, indicating the presenceof at least one additional gene, deletion of which causes azoospermia.     

Histamine N-methyltransferase inhibitor potentiates histamine- and antigen-induced airway microvascular leakage in guinea pigs

Background: Histamine N-methyltransferase (HMT) modulates histamine- and antigen-induced bronchoconstriction. However, it is unclear whether vascular permeability evoked by an allergic reaction can be exaggerated by inhibition of HMT activity. Methods: We studied the effects of intravenously injected SKF 91488, a specific HMT inhibitor, on increases in plasma extravasation induced by intravenously injected histamine in unsensitized guinea pigs and by intravenously injected ovalbumin antigen in guinea pigs sensitized to ovalbumin in vivo with Evans blue dye as a marker. Results: Pretreatment with SKF 91488 shifted, in a dose-dependent fashion, the dose-response curves of the leakage of dye to histamine to lower concentrations in the trachea, main bronchi, and nasal mucosa. Likewise, pretreatment with SKF 91488 (20 mg/kg intravenously) significantly increased the leakage of dye induced by ovalbumin antigen (200 μg/kg intravenously) in three parts of the airway (p < 0.05). In contrast to SKF 91488, intravenously injected aminoguanidine, a specific inhibitor of diamine oxidase (16 mg/kg intravenously), did not alter the leakage of dye induced by histamine (from 0.001 μg/kg to 10 μg/kg intravenously) (p > 0.20). HMT activities were observed in the nasal mucosa, as well as in the trachea and main bronchi, as shown in a previous study. Conclusion: These findings suggest that HMT modulates the effects of exogenous histamine and endogenously released histamine induced by antigen challenge on plasma extravasation in the airway in guinea pigs in vivo. (J ALLERGY CLIN IMMUNOL 1995;96:910-6.)     

A study of human interstitial lung diseases with special reference to immune complexes and hyaline membrane

To evaluate the pathogenetic roles of immune complexes and alveolar hyaline membrane in idiopathic interstitial pneumonia (IIP), immunohistological and ultrastructural studies of the kidney and lung were performed in 23 cases of IIP, 19 cases of autoimmune diseases, 17 cases of interstitial pneumonia other than IIP, and 11 cases of bronchopneumonia as a control group. None of the cases of IIP or interstitial pneumonia other than IIP showed immune complexes in the alveolar and glomerular capillary walls. On the other hand, one case of SLE was positive for IgG and components of complement along the alveolar and glomerular capillary walls. The alveolar hyaline membrane in the present cases revealed immunoglobulins as well as components of complement, which were poorly soluble in chaotropic solution or acidic buffer. These results indicate that circulating immune complexes play a minor role in the pathogenesis of IIP and other types of interstitial pneumonia, and that there is no relationship between immune complex deposition in alveoli and the alveolar hyaline membrane. It is necessary to further investigate factors other than immune complexes involved in alveolar tissue damage and to clarify the significance of the hyaline membrane in the processes occurring from acute changes to pulmonary fibrosis in IIP.     

Two case reports of childhood liver cell adenomas harboring beta-catenin abnormalities

The benign epithelial neoplasm liver cell adenoma is rare, especially in childhood. We report 2 such cases, 1 of which was associated with Prader-Willi syndrome. Differential diagnosis of the liver cell adenomas on the basis of histopathologic findings proved difficult and was based on the absence of cellular and nuclear atypia, mitotic activity, and invasive growth. In both cases, immunohistochemical staining demonstrated the nuclear accumulation of beta-catenin, and in 1 case, the tumor cells carried a mutation of the beta-catenin gene. Recently, disregulation of the Wnt/beta-catenin pathway, attributable to abnormalities of the beta-catenin gene, has been reported to be a major event in the development of hepatocellular carcinomas and hepatoblastomas. Our report may be the first to describe the beta-catenin abnormalities in childhood liver cell adenoma. These findings imply that abnormalities of beta-catenin can be an early initiating event in human liver tumorigenesis.