Oesophageal squamous cell carcinoma with lymphoid stroma

Summary We treated a 70-year-old Japanese man with squamous cell carcinoma of the oesophagus with evidence of lymphoid stroma. The tumour consisted of a main lesion invading the muscular layer of the oesophagus, in association with wide areas of carcinoma in situ. The tumour stroma of the lesion was nondesmoplastic and was uniformly infiltrated mainly by abundant lymphocytes and plasma cells. Immunohistochemically, the lymphocytes consisted of a large number of T lymphocytes and a small number of B lymphocytes. S-100 protein positive cells were marked in the tumour cell nests and necrotic change of tumour cells was frequent. Abundant infiltration of lymphocytes and plasma cells was also wide-spread beneath the carcinoma in situ, together with the lymphoid follicles. Carcinoma with lymphoid stroma can occur not only in the breast, uterine cervix, nasopharynx and stomach but also in the oesophagus.     

Dynamic characteristics of carotid sinus pressure-nerve activity transduction in rabbits

The dynamic characteristics of the baroreflex neural arc from pressure input to efferent sympathetic nerve activity (SNA) reveal derivative characteristics in the frequency range of 0.01 to 0.8 Hz (i.e., the baroreflex gain augments with increasing frequency) and high-cut characteristics in the frequency range above 0.8 Hz (i.e., the baroreflex gain decreases with increasing frequency) in rabbits. The derivative characteristics accelerate the arterial pressure regulation via the baroreflex. The high-cut characteristics preserve the baroreflex gain against pulsatile pressure by attenuating the high-frequency components less necessary for arterial pressure regulation. However, to what extent the carotid sinus baroreceptor transduction from pressure input to afferent baroreceptor nerve activity (BNA) contributes to these characteristics remains unanswered. To test the hypothesis that the carotid sinus pressure-BNA transduction partly explains the derivative characteristics but not the highcut characteristics, we examined the dynamic BNA response to pressure input in the frequency range from 0.01 to 3 Hz by using a white noise analysis in 7 anesthetized rabbits. The transfer function from pressure input to BNA showed slight derivative characteristics in the frequency range from 0.01 to 0.3 Hz with approximately a 1.7-fold increase in dynamic gain, but it showed no high-cut characteristics. In conclusion, the carotid sinus baroreceptor transduction partly explained the derivative characteristics but not the high-cut characteristics of the baroreflex neural arc. The present results suggest the importance of the central processing from BNA to efferent SNA to account for the overall dynamic characteristics of the baroreflex neural arc.     

A new model-based method of reconstructing central aortic pressure from peripheral arterial pressure

We have shown in our previous study that the transfer function between central aortic pressure and tonometric radial arterial pressure can be modeled as a pure elastic lossless tube terminated with a modified Windkessel. We hypothesized, using the model-derived radial arterial flow, that central pressure could be reconstructed by adding the time-shifted forward and backward pressure components (Stergiopulos et al.: Am J Physiol 274: H1386---H1392, 1998). In eight patients (age 16--75), central micromanometric and radial arterial tonometric pressure were measured simultaneously. We imposed measured tonometric pressure to the terminal modified Windkessel to estimate radial arterial flow, with which tonometric pressure was separated into forward and backward components. These components were then appropriately time shifted, and summed to central pressure. We used average parameter values for the terminal impedance, but individualized the transmission delay. The poor correlation (r(2)) between tonometric and central pressure (0.264--0.765) was improved by both central pressure reconstruction methods (generalized transfer function: 0.887--0.974, model-based method: 0.849--0.979). The sensitivity analysis indicated that the key model parameter in reconstructing central pressure was the transmission delay. We conclude that our model-based method was capable of reconstructing central pressure as precisely as the generalized transfer function method, and also capable of individualizing the transfer function by changing the transmission delay.     

THE BEHAVIOUR OF LYMPHOGENEOUSLY GIVEN ANTIGEN IN THE LYMPH NODE THE LOCALIZATION OF GIVEN ANTIGEN and NEWLY FORMED ANTIBODY

The vascular structures in the lymph node and their relation to fluid exchange have been reported in previous communications and it was considered that the morphological changes of the vascular structures were closely correlated with the functional development of lymph nodes as an antibody forming organ. In order to clarify the localization of the given antigen and newly formed antibody in relation to the morphological structure of lymph nodes, the popliteal lymph nodes of rabbits were studied by immuno-fluorescent techniques.
The antibody was found in the pavement arrangement (solid) of reticulum tissue which was formed by the expel of lymphocytes in the cortical mass and by the morphofunctional alterations of the reticulum cells. The given antigen and newly formed antibody were never detected in the follicles throughout the period of this experiment. ACTA PATH. JAP. 22:427–440, 1972.     

Intra-bone marrow-bone marrow transplantation facilitates hemopoietic recovery including dendritic cells

In this report, we provide evidence using a serial bone marrow transplantation (BMT) protocol that intra-bone marrow (IBM)-BMT (IBM-BMT) can efficiently reconstitute the hemopoietic system with cells of donor origin, in contrast to conventional intravenous (IV)-BMT (IV-BMT). Furthermore, the hematolymphoid system of secondary recipients that had received bone marrow cells (BMCs) from primary recipients treated with IBM-BMT recovered earlier than that of the secondary recipients of BMCs from primary recipients treated with IV-BMT. This was the case when the Lin-/c-kit+ progenitor cells of the secondary and tertiary recipients were examined. These findings indicate that IBM-BMT can facilitate the development of not only cells of various lineages but also the effective generation and, more importantly, the maintenance of the progenitor cells. Furthermore, we show that IBM-BMT can reconstitute the dendritic cell (DC) subsets (myeloid and lymphoid DCs), which are critical for the initiation of both adaptive and innate immune responses. The frequency of both myeloid and lymphoid DC subsets was approximately equal to that of normal age-matched untreated controls and, after second and third BMT, this ratio was close to that observed in the normal controls. However, the lymphoid DCs were clearly reduced in the secondary and tertiary recipients of BMCs from mice that had received IV-BMT. Therefore, the development of DC subsets is also normally maintained in the IBM-BMT group.     

Closed-loop identification of carotid sinus baroreflex transfer characteristics using electrical stimulation

Although random aortic pressure (AOP) perturbation according to a binary white noise sequence enables us to estimate open-loop dynamic characteristics of the carotid sinus baroreflex under closed-loop conditions, the necessity of arterial catheter implantation limits the applicability of this method in freely moving animal experiments. Thus, we explored a closed-loop system identification method using electrical stimulation. In 6 anesthetized and vagotomized rabbits, we stimulated the aortic depressor nerve with a binary white noise sequence (0-10 Hz) under baroreflex closed-loop conditions while measuring cardiac sympathetic nerve activity (SNA) and AOP. We used a closed-loop identification method to estimate the peripheral arc transfer function from SNA to AOP. The peripheral arc transfer function approximated a second-order low-pass filter and its fitted parameters did not differ from those obtained by an open-loop identification method (dynamic gain: 1.16+/-0.32 vs. 1.02+/-0.11; natural frequency: 0.08+/-0.03 vs. 0.09+/-0.03 Hz; damping ratio: 1.53+/-0.15 vs. 1.57+/-0.21). In 6 different rabbits, we applied intermittent rapid pacing (396 beats/min) under baroreflex closed-loop conditions to estimate the neural arc transfer function from AOP to SNA. The neural arc transfer function approximated a first-order high-pass filter and its fitted parameters did not differ from those obtained by an open-loop identification method (dynamic gain: -1.15+/-0.45 vs. -1.06+/-0.05; corner frequency: 0.12+/-0.05 vs. 0.13+/-0.03 Hz). In conclusion, the closed-loop identification method using electrical stimulation is effective to estimate the neural and peripheral arc transfer functions.     

Studies on the behavior of peritoneal cells against soluble immune complexes using the “agar-bullet” method

The results of our previous investigation indicated that the reaction of intraperitoneal cells against foreign materials depended on the heterogenicity and the molecular weight of the substance (Takeuchi, 1973). Substances tested for cellular reaction in this agar-bullet method were (1) bovine serum albumin, (2) soluble antigen-antibody complexes, (3) mixtures of bovine serum albumin and rabbit gamma globulin, (4) precipitated complexes, and (5) bovine gamma globulin. The soluble complex prepared with excess antigen in vitro showed a marked cellular reaction, which was considered to be due to its heterogenicity and molecular weight.     

Adriamycin-induced DNA strand breaks in HeLa and in P388 leukaemia cells detected using in situ nick translation

DNA strand breaks produced by adriamycin (ADR) were measured in HeLa cells and ADR-sensitive and -resistant P388 leukaemia cells, using the in situ nick translation method. The break sites in the DNA were translated artificially in the presence of Escherichia coli DNA polymerase I and 3H-labelled dTTP, and were visualized by autoradiographic observation of the grains. The DNA strand breaks in the HeLa cells increased in a dose-dependent manner, compared with findings in the untreated control cells, i.e., 15.2 fold at 20 micrograms/ml of ADR for 1 h. This level correlated with DNA single-strand breaks detected by the alkaline elution method. DNA breaks were also noted in the ADR-sensitive P388 cells, but in the ADR-resistant cells the level of DNA strand breaks was low. The enhanced cytotoxicity is apparently the consequence of the enhanced potential of ADR to cause breaks in the DNA strands. Our findings show that the survival response of the cells decreases and the level of DNA strand breaks increases following exposure to ADR. ADR resistance may be mediated by a reduction in the level of DNA strand breaks.     

Selective effects of Lipiodolized antitumor agents

Lipiodol Ultra-Fluid (Lipiodol) remains selectively in the tumor for an extended time when applied through arteries feeding the tumor. Although lipophilic antitumor drugs are selective when combined with Lipiodol, wide application of common hydrophilic agents is limited, as these compounds are insoluble in oil. We propose "Lipiodolization" of water-soluble agents using as an intermediate Urografin, a water-soluble contrast medium. Thirteen patients with primary hepatocellular carcinoma were treated with this Lipiodol-Urografin system containing antitumor agents. Marked decrease in serum alpha-fetoprotein (AFP) levels, decrease in tumor size in the hepatic imaging, and histologic studies of the resected specimen revealed this mode of therapy to be effective in 10 of 13 patients (77%) with hepatocellular carcinoma. Lipiodolization of antitumor agents is a new approach to selective cancer chemotherapy.     

Dietary Olive Oil Intake Improves Running Endurance with Intramuscular Triacylglycerol Accumulation in Mice

Olive oil is a functional food shown to have a variety of bioactive effects. Therefore, we expect it to be a novel functional food with an exercise-mimetic effect on skeletal muscles. This study aimed to investigate the effect of olive oil on the endurance capacity and muscle metabolism in mice. Mice fed a 7% (w/w) olive oil diet for eight weeks showed improved treadmill running endurance and increased intramuscular triacylglycerol (IMTG) accumulation in the gastrocnemius muscle compared to soybean oil diet-fed controls. The increase in running endurance with olive oil intake was independent of the muscle fiber type. To elucidate underlying the mechanism of elevated IMTG levels, we examined the expression levels of the genes related to lipid metabolism. We found that the expression of diacylglycerol O-acyltransferase1 (DGAT1) was significantly upregulated in the muscle of olive oil diet-fed mice. In addition, the olive oil diet-fed mice showed no metabolic impairment or differences in growth profiles compared to the controls. These results suggest that dietary olive oil intake affects muscle metabolism and muscle endurance by increasing energy accumulation.