Transient induction of single GST-P positive hepatocytes by DEN

The single cells positive for placental glutathione S-transferase(GST-P), detectable in livers of rats soon after treatment withhepatocarcinogens, are possible ‘initiated cells’,the hypothesis tested in the present series of experiments.No low dose threshold was observed in male Sprague-Dawley ratsat different single doses of diethylnitrosamine (DEM) althougha plateau was reached between 160 and 200 mg/kg body weight.At the latter single dose 12 400 positive cells/cm³ were observedimmunohistochemically in rat livers after one week, the numbersthen decreasing to week 8 and thereafter rising again. In thenumbers then decreasing to week 8 and thereafter rising again.In the early stages single cells predominated but with timea gradual increase in mini-foci and larger lesions became evident.Application of selection pressure (feeding of diet containing0.02% 2-AAF plus partial hepatectomy) to rats 2–24 weeksafter single DEN-treatment resulted in the formation of largefoci positive for GST-P, especially in the early stages, thegrowth response being less pronounced with time. The numberof foci, on the other hand. was correlated with the number offoci, on the other hand, was correlated with the number ofsingle cells/mini-foci detected inhepatectomy tissue of thesame individuals. These results suggest that the early GST-Ppositive populations could be the precursor for preneoplasticfoci and nodules.     

A young adult male with primary carcinoma of the jejunum

A 37-year-old male was admitted to our hospital because of epigastric pain and weight loss. He was in a stable state of health until 2 months earlier but gradually worsened and lost weight about 13 kg during 1 month. After 1 month, he consulted our clinic. Upper GI barium studies revealed malignant stenosis in about 50 cm from the ligament of Treitz. Radical surgical resection was performed including the segment in 25 cm of intestine containing the primary tumor. Lymph node and liver metastases were not seen. Pathologic findings revealed "well differentiated adenocarcinoma". Thirteen months after the operation, he is well and has gained weight to state of health.     

Bio-adhesio-chemo (BAC) therapy for patients with malignant pleural effusion

Eighteen patients with serious pleuritis carcinomatosa with remarkable pleural effusion were treated with a new pleurodesic therapy, and all the patients treated obtained favorable results. After removing pleural effusion, fibrinogen solution was intrapleurally instilled and then, our newly devised material, G.T.XIII and an anticancer drug, Adriamycin (ADM), were administered as chemosclerosing agents in an attempt to prevent recurrence of the effusion and also to provide locoregional antineoplastic effects. Recurrence of pleural effusion was nil in all patients treated, and subjective complaints of the patients were remarkably relieved. There were 14 patients evaluable, and all the response of these patients resulted in partial response (PR) according to the World Health Organization (WHO) criteria. Improvement of performance status (PS) was observed in 61% (11/18). Eight patients could be discharged. Three patients have remained alive. Fifteen patients died after the therapy, and their median survival was 67 days. Eight patients were autopsied. The postmortem examinations confirmed that fibrous adhesion in the pleural cavity with these materials was significant, and evidence of recurrence of pleural fluid was not seen. Topical oncolytic effects of the ADM were histologically remarkable. This pleurodesis was called "Bio-adhesio-chemo (BAC) therapy."     

Reduced-intensity unrelated cord blood transplantation for patients with advanced malignant lymphoma.

We report the results of reduced-intensity unrelated cord blood transplantation (RI-UCBT) in patients with advanced malignant lymphoma. Twenty patients (median age, 46.5 years; range, 27-66 years) underwent RI-UCBT with a preparative regimen consisting of fludarabine 125 mg/m2 , melphalan 80 mg/m 2 , and 4 Gy of total body irradiation. The median infused total cell dose was 2.75 x 10(7)/kg (range, 2.3-3.4 x 10(7)/kg). Graft-versus-host disease (GVHD) prophylaxis was composed of cyclosporine or tacrolimus alone. Fifteen patients achieved primary neutrophil engraftment after a median of 20 days. Eight patients developed grade II to IV acute GVHD, and 2 developed chronic GVHD. Of the 16 patients with evaluable disease, 10 achieved a complete response. Primary disease recurred in 1 patient, and transplant-related mortality within 100 days occurred in 8 of 20 patients. The estimated 1-year probability of progression-free survival was 50%. These data suggest that RI-UCBT is a feasible option for patients with refractory lymphoma who lack an HLA-matched donor.     

Gaps and fragmentation of the superficial cortex in the abdominal and pelvic lymph nodes of elderly Japanese

Gaps and fragmentation of the superficial lymph node cortex are considered to provide intranodal shunt flow between the afferent and efferent vessels. Using serial sections of 205 nodes obtained from 27 donated cadavers more than 70 years of age, we examined the histological architecture of the abdominal and pelvic nodes in elderly Japanese. Secondary follicles were rare in the specimens. Cortex gaps were, to a greater or lesser degree, found in all nodes. We classified these nodes into three types according to how often the gap occurred. Type 1 nodes, with a relatively complete shield for the afferent lymph, were most frequently found in gastric nodes, whereas type 3 nodes, with numerous gaps, were often observed in the colic, para-aortic and pelvic nodes. The type 3 nodes showed a specific architecture characterized by a fragmented superficial cortex, three-dimensionally assembled cords and a common sinus between them. Primary follicles were located in the assembled cord structures as well as at the superficial cortex. Irrespective of the type, B and T lymphocyte areas were intermingled in the cortex-like areas. The present results reveal region-specific histological heterogeneity in aged human visceral nodes. Due to increased surface areas, the type 3 architecture seemed to accelerate systemic immunity rather than act as a local barrier in the para-aortic and pelvic nodes, which are located centrally along the lymphatic drainage routes. However, thick trabeculae often seemed to develop in the type 3 sinus to decrease nodal function with aging.     

Expression of connexin 32 gap junction protein in the kidneys during fetal development of the hamster (Mesocricetus auratus)

The expression of gap junction protein was examined immunohistochemically using affinity-purified antibody against rat liver gap junction protein, connexin 32 (Cx32), in the kidneys of fetal (gestation days 13–16) and adult Syrian golden hamsters. Phalloidin histochemical staining, PNA- and RCA I-lectin stainings, NCAM immunostaining, and alkaline phosphatase and Na⁺-K⁺-ATPase enzyme-histochemical staining were performed in combination with Cx32 immunostaining. The kidney sections were observed with a confocal scanning laser microscope. By gestation day 13, Cx32 immunoreactivity was observed in the differentiating tubules. The Cx32 staining was localized on the lateral cell membrane of the cells lining the developing proximal tubules, while the S-shaped bodies, developing distal tubules, and collecting tubules showed no positive immunostaining. As the kidney developed, the density of Cx32 immunoreactivity increased. As the gap junction provides pathways for cell-cell communication, the development of Cx32 expression may imply that this structure plays an important role in renal tubule development. Confocal scanning laser microscopy provided a clear image of the fluorescence-labeled cell structures, free from out-of-focus blur. Using the same sections, stereoscopic images were easily reconstructed from serial optical sections, and were helpful in understanding the spatial distribution of Cx32 expression in the developing fetal proximal tubules.     

Effect of Enamel Prism Decussation and Chemical Composition on the Biomechanical Behavior of Dental Tissue: A Theoretical Approach to Determine the Loading Conditions to Which Modern Human Teeth are Adapted

This theoretical study explored whether the directions of loads to which modern human molars are commonly subjected to are reflected in the biomechanical behavior of the tissue itself. A detailed finite element model of a piece of decussating enamel (M³ paracone) was created, taking into account differences in crystal orientation between the prism head and the interprismatic matrix, and was tested under differently angled mediolateral loads (i.e., mimicking various stages of the chewing cycle). Second, although teeth are highly mineralized, they also contain organic material and water, while in modern humans, there are systematic differences in chemical composition from the outer enamel surface to the dentinoenamel junction. To test the biomechanical effects of this gradient in mineralization a second set of models with gradually changing properties was created and subjected to the same loads. Chemically heterogeneous enamel yielded overall lower stress levels than homogenous enamel, especially at extreme loading angles. However, the general trends regarding the increase in tensile stresses at more oblique angles, and the number of nodes exhibiting tension, were comparable between the different set‐ups. The findings support suggestions that (a) the biomechanical behavior of dental tissue is the combined result of micromorphology and chemical composition and (b) that the range of loading directions, to which teeth are normally subjected to, can be inferred from dental microanatomy. For (palaeo)biological applications, the findings suggest that the absolute strength of teeth (e.g., bite force) cannot be predicted with certainty, whereas kinematic parameters of the masticatory apparatus can. Anat Rec, 2007. © 2008 Wiley‐Liss, Inc.     

Delta-like 1 is necessary for the generation of marginal zone B cells but not T cells in vivo

Notch receptors and their ligands contribute to many developmental systems, but it is not apparent how they function after birth, as their null mutants develop severe defects during embryogenesis. Here we used the Cre-loxP system to delete the Delta-like 1 gene (Dll1) after birth and demonstrated the complete disappearance of splenic marginal zone B cells in Dll1-null mice. In contrast, T cell development was unaffected. These results demonstrated that Dll1 was dispensable as a ligand for Notch1 at the branch point of T cell-B cell development but was essential for the generation of marginal zone B cells. Thus, Notch signaling is essential for lymphocyte development in vivo, but there is a redundancy of Notch-Notch ligand signaling that can drive T cell development within the thymus.