Morphometric difference in the human maxillary nerve fibers between dentulous and edentulous jaw subjects

This study was conducted to quantify the change in the number and size of myelinated nerve fibers of the maxillary nerve with tooth loss in humans. We carried out a morphometric analysis to compare the number and size of myelinated nerve fibers in the human maxillary nerve between four dentulous and four edentulous jaw cases. Our results indicated that the number of axons decreased by approximately 13,000 with tooth loss. The average size of axons remained unchanged, but there was a change in the fiber size distribution, namely the loss of a large number of small-sized axons was accompanied by the total disappearance of small number of large-sized axons.     

Glyceraldehyde 3-phosphate dehydrogenase is a novel autoantigen leading autoimmune responses to proliferating cell nuclear antigen multiprotein complexes in lupus patients

Using 2-dimensional electrophoresis and ion-pair chromatography, we have identified elements of proliferating cell nuclear antigen (PCNA) multiprotein complexes that are reactive to antibodies in sera from patients with systemic lupus erythematosus. Among the various elements of the complexes, a 37 kDa protein (PI 8.5) that specifically reacted with SLE sera, but not with sera from patients with other connective tissue diseases, was identified as glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Immunoblot analysis showed that SLE sera reactive with the 37 kDa protein specifically reacted with GAPDH, as did anti-GAPDH mAbs. The purified autoantibodies to GAPDH from lupus serum showed both nuclear speckled and cytoplasmic staining patterns in immunofluorescence on Hep-2 cells. In addition, enzyme-linked immunosorbent assay (ELISA) revealed the presence of anti-GAPDH autoantibodies in 47% of lupus patients. Longitudinal analysis of the reactivity of lupus sera to PCNA complexes showed the autoimmune response to spread from GAPDH to other elements of PCNA complexes, and the presence of anti-GAPDH antibodies was significantly correlated with increased levels of serum PCNA. Taken together, these findings suggest that GAPDH interacting with PCNA in association with its cellular function is a novel autoantigen recognized by lupus sera, and that GAPDH thus plays an important role in the induction of autoimmune responses against the PCNA complex.     

Apoptosis with FasL+ cell infiltration in the periphery and thymus of corrected autoimmune mice.

Fas (CD95) ligand (L) is a death factor that binds to its receptor, Fas, and induces apoptotic cell death, a crucial process in immunological tolerance. gld (generalized lymphoproliferative disorder) mice, which have a point mutation in the FasL gene, develop spontaneous systemic autoimmune syndromes characterized by hypergammaglobulinaemia and lymphoid hyperplasia owing to accumulation of abnormal B220+ CD3+ cells. Transplantation of wild-type (wt) bone marrow cells into old gld mice on the same strain background results in normalization of autoimmune syndromes. We characterized the cellular mechanisms (functionally and histologically) of the above phenomena in gld mice after bone marrow transplantation (BMT) to determine the role of apoptosis via Fas/FasL interactions in inducing and maintaining self-tolerance in vivo. Activated splenocytes from wt and BMT (wt to gld) mice showed significant cytotoxic activity against Fas transfectant cells while those from BMT (gld to gld) mice did not. Cells in the thymus, spleen and lymph nodes of gld mice uniformly upregulated Fas expression and were sensitive to Fas-mediated apoptosis compared with those in wt mice. Cells sensitive to Fas-mediated apoptosis in gld mice resided not only among abnormal B220+ CD3+ cells but also among conventional lymphocytes. More importantly, histological analysis revealed that cells in the spleen, lymph nodes and thymus frequently underwent apoptosis with infiltration of FasL+ cells in BMT (wt to gld) mice compared with BMT (gld to gld) mice. Our results indicated that apoptosis via Fas/FasL interactions can directly eliminate pathogenic cells responsible for autoimmunity in the periphery and possibly in the thymus in vivo.     

Etiological Study of Diarrheal Patients in Vientiane, Lao People’s Democratic Republic

The etiological agents of diarrhea in Vientiane, Lao People’s Democratic Republic (Lao PDR), were studied in the period from October 1996 to August 1997. A total of 880 patients with diarrhea visiting medical facilities were examined for Shigella, Salmonella, diarrheagenic Escherichia coli, Vibrio, Aeromonas, Campylobacter, and rotavirus. Shigella spp., heat-stable enterotoxin (ST)-producing E. coli, and serogroup-based enteropathogenic E. coli were found to be the main organisms causing diarrhea in Vientiane, with frequencies of 16.8% (148 of 880), 17.2% (111 of 645), and 11.0% (97 of 880), respectively. Relatively low incidences were observed in the cases of Salmonella spp., (0.6%; 5 of 880), Campylobacter spp. (4.4%; 39 of 880), and rotavirus (6.1%; 9 of 148), and no isolates of V. cholerae O1 or O139 or Aeromonas were recovered. An analysis of the incidences of enteropathogens with respect to age and seasonal variations demonstrated that the frequencies of isolation of Shigella spp. and heat-labile enterotoxin-producing E. coli were significantly higher in those aged 1 to 5 years than in those younger than 1 year of age and those older than 5 years of age (P < 0.0001 and P < 0.05, respectively) and that the frequencies of isolation of Shigella spp. and ST-producing E. coli were significantly higher in the rainy season than in the dry season (P < 0.005 and P < 0.001, respectively). Almost all strains of Shigella spp. tested were resistant to ampicillin, tetracycline, and erythromycin and were susceptible to cefdinir and ofloxacin. This is the first intensive and longitudinal study to define the etiologic agents of diarrheal diseases in Lao PDR.     

Immunohistochemical studies on oncogene products (EGF-R,c-erbB-2) and growth factors (EGF,TGF-α) in human breast cancer: their relationship to oestrogen receptor status,histological grade,mitotic index and nodal status

Summary In this investigation, 83 human mammary carcinomas were examined for the expression of oestrogen receptor (ER), epidermal growth factor receptor (EGF-R), epidermal growth factor (EGF), transforming growth factor alpha (TGF-), c-erbB-2, histological grade, mitotic index and nodal status, all of which are reportedly prognostically significant factors (Bloom and Richardson 1957; Baak et al. 1985; Wright et al. 1989). ER expression was biochemically recognized in 43.4% of mammary carcinomas, and EGF-R, EGF, TGF- and c-erbB-2 were histochemically recognized in 25.3, 14.5, 27.7 and 18.0% of mammary carcinomas examined respectively, using conventional sections of buffered formalin-fixed, paraffin-embedded tissue and monoclonal or polyclonal antibodies. There were significant relationships between negative ER and positive EGF-R or TGF-; positive EGF-R and TGF-; positive EGF-R and c-erbB-2; and positive c-erbB-2 and TGF-. The single changes which were the negative ER and the positive c-erbB-2 correlated with histological grade and mitotic index. Co-expression of EGF-R and TGF- correlated with positive nodal status. Therefore, the present investigation indicates that the negative ER, single expression of c-erbB-2 and co-expression of EGF-R and TGF- are important markers which contribute indirectly to prognosis, which reconfirms previous findings on the former two while adding the new finding that immuno-histochemical demonstration of expression of EGF-R and TGF- may provide useful information for selecting the appropriate treatment.     

An electron microscopic study of neurosecretion in the cerebral ganglion of the earthworm

Non-synaptic, exocytotic release of neurosecretory granules in cerebral ganglion neurons was observed electron microscopically in 3 species of the oligochaete annelids Aporrectodea caliginosa, Octolasion cyaneum and Lumbricus terrestris. In addition to the features indicating exocytotic release of neurosecretory granules into perineuronal space, possible features of neurosecretion into blood vessels were seen within the cerebral ganglion. Axon terminals in synaptic contact with perikaryal profiles of cerebral ganglion neurons were also found.     

Blood flow velocity in the common carotid artery in humans during graded exercise on a treadmill

Cerebral blood volume flow and flow velocity have been reported to increase during dynamic exercise, but whether the two increase in parallel and whether both increases occur as functions of exercise intensity remain unsettled. In this study, blood flow velocity in the common carotid artery was measured using the Doppler ultrasound method in eight healthy male students during graded treadmill exercise. The exercise consisted of stepwise progressive increases and decreases in exercise intensity. The peak intensity corresponded to approximately 85% of maximal oxygen consumption. During this exercise, the heart rate (f _c), mean blood pressure (BP) in the brachial artery and mean blood flow velocity (_cc) in the common carotid artery increased as functions of exercise intensity. At the peak exercise intensity, (f _c), BP and _cc increased by 134.5%, 20.5% and 51.8% over the control levels before exercise (P < 0.01), respectively. The resistance index (RI) and pulsatility index (PI) were determined from the velocity profile and were expected to reflect the distal cerebral blood flow resistance. The RI and PI increased during the graded exercise, but tended to decrease at the highest levels of exercise intensity. As _cc increased with increases in exercise intensity it would be expected that cerebral blood flow would also increase at these higher intensities. It is also suggested that blood flow velocity in the cerebral artery does not proportionately reflect the cerebral blood flow during dynamic exercise, since the cerebral blood flow resistance changes.     

The value of external morphology in the identification of larval anisakid nematodes: a scanning electron microscope study

We studied larval nematodes of four genera of the Anisakidae using a scanning electron microscope (SEM). The anterior and posterior extremities and cuticular structures of the 3rd-stage larvae (L3) ofAnisakis type I,Pseudoterranova decipiens, Contracaecum type B andHysterothylacium were examined. The 4th-stage larvae (L4) ofAnisakis type I,P. decipiens, recovered after infection into laboratory rats, and the L3 and L4 ofAnisakis type I larvae from human were also examined in the same way. There were generic differences in the shape and size of the lip bulges, external papillary structures, the appearance of the boring tooth, the width and depth of the grooves and ridges of the cuticle and the caudal structures of the L3. InAnisakis type I andP. decipiens L3, changes were seen in the anterior extremity, cuticle and posterior extremity after molting to the L4. Similar changes can be expected in larvae infecting man. The L4 ofAnisakis type I from rat and man were similar, while the L4 ofAnisakis type I andP. decipiens showed differences. These ultrastructural differences might be of value in the identification of fragments recovered during endoscopy in man.     

Hyperplastic epithelial foci in honeycomb lesions in idiopathic pulmonary fibrosis

Seventy-two cases of idiopathic pulmonary fibrosis (IPF) were examined from 2856 consecutive autopsy cases at the Japanese Red Cross Medical Center in Tokyo from 1973-1996. Primary lung cancer had arisen in 31 of 72 cases of IPF (43%), significantly higher than the incidence in cases without IPF (8.1%) and in the cases with non-IPF chronic lung diseases (11.9%). Hyperplastic epithelial foci in the honeycomb lesions of IPF cases were significantly more prominent in the lower than in the upper lobe, in cases with or without lung cancer, and they were more prominent in the lower lobe of IPF with than in those without cancer. The length of hyperplastic epithelial foci in the lower lobe of IPF cases was longer than that in interstitial pneumonia-associated with collagen vascular diseases. There was a higher PCNA labeling index of hyperplastic epithelial foci in IPF cases than in cases of interstitial pneumonia-associated with collagen vascular diseases. The PCNA labeling index was almost the same between smokers and nonsmokers with IPF. Overexpression of p53 was observed in hyperplastic epithelial foci in honeycomb lesion of IPF. DNA ploidy analysis of hyperplastic epithelial foci in the paraffin sections of 12 IPF cases revealed aneuploidy patterns in eight cases. These results strongly suggest that accelerated cell proliferation occurs in the honeycomb lesion of IPF, and that regenerative epithelia becomes susceptible to carcinogenic agents in addition to the smoking effect.