[The treatment of renal cell carcinoma with interferon].
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Biomedical subjects
Publications and source records attributed to K Miki.
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The relationship between methylation and expression of rat pepsinogen 1 (Pg1) genes was investigated in various tissues. On Northern blotting with a Pg1 complementary DNA probe, Pg1 mRNA was detected only in the glandular stomach of normal rats. Methylation analysis with Msp1/HpaII and Hha1 revealed tissue specific methylation patterns of Pg1 genes with less methylated in the stomach than in other normal tissues not expressing the genes. During stomach development, there was a progressive increase in the Pg1 mRNA level that almost coincided with change in the mucosal pepsinogen level and progressive demethylation after the onset of transcription. Thus, there was an inverse correlation between methylation and expression of Pg1 genes, suggesting a role of DNA methylation in Pg1 gene regulation during normal differentiation, although not its primary role in gene activation. There was no detectable Pg1 mRNA in either primary or transplanted stomach cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine. The methylation patterns of Pg1 genes were different from those of normal tissues that expressed the gene and of those that did not and no simple correlation was observed between methylation and expression of Pg1 genes. This result is consistent with a previous finding that DNA methylation is deranged in tumor cells.
We have examined the correlation between the extents of methylation and expression of pepsinogen A genes in normal human tissues. Expression of pepsinogen A mRNA was detected only in the fundic mucosa of the stomach and both CCGG and GCGC sites in the genes region were less methylated in the fundic mucosa than in other non-expressing tissues. Thus, there was an inverse correlation between the extents of methylation and expression of pepsinogen A genes and the role of DNA methylation in the regulation of pepsinogen A genes expression during normal differentiation was suggested.
Gastric phenotypic expression indicated by paradoxical concanavalin A (Con A) staining for class III mucins and the immunoperoxidase method for pepsinogen (Pg) I and Pg II was found in pyloric gland metaplasia of gallbladder epithelium. Using the same methods, the features of gallbladder cancers and their relationship to pyloric gland metaplasia in the human gallbladder epithelium were studied. Histologically, 57 gallbladder cancers were classified into 5 papillary adenocarcinomas, 29 tubular adenocarcinomas, 8 poorly differentiated adenocarcinomas, 6 signet-ring cell carcinomas, 4 mucinous adenocarcinomas, and 5 squamous cell carcinomas. In papillary and tubular adenocarcinomas, Pg I and/or Pg II staining was detected in 80% and 75.9% of cancers, respectively. Pg II staining was significantly more frequent than Pg I staining. One signetring cell carcinoma also had Pg II activity. Pyloric gland metaplasias all contained class II mucins and were further classified into complete type and incomplete type on the basis of presence or absence Pg I and/or Pg II activities. A few cancer cells with class III mucins were negative for Pg staining; conversely, a few cells with Pg I and/or Pg II had no class III mucins. Phenotypic diversity in both class II mucin reactivity and Pg activities was observed in gallbladder cancer cells with the pyloric gland cell type. By comparison, pyloric gland metaplasia varied only in Pg activities. A few Pg-positive cancers were found in the gallbladder with Pg-negative pyloric gland metaplasia. The present results clearly indicate the appearance of gastric phenotypic expression in both gallbladder epithelium and gallbladder cancers and suggest the independent induction of pyloric gland metaplasia and cancer with gastric phenotypic expression.
The differentiation of F9 cells, as monitored by the secretion of basement membrane proteins, was biphasic depending on the dose of retinoic acid (RA) used. Secretion of laminin A reached a plateau at about 10 nM and increased again at more than 100 mM RA. A similar biphasic response was observed in the secretion of tissue-type plasminogen activator as well. In the presence of RA alone, this biphasic pattern of differentiation was stable for a long period of time, but the addition of 1 mM dibutyryl cAMP changed it to monophasic after 12 days of exposure.
We constructed a recombinant vaccinia virus (RVV) expressing envelope (env) glycoprotein (gp51) of bovine leukaemia virus (BLV): the expression of gp51 was detected by Western blot of the lysates of rabbit kidney cells infected with the RVV. The rabbits inoculated intradermally with the RVV alone failed to induce detectable anti-gp51 antibodies even 10 weeks after immunization. However, when these animals were boosted with inactivated BLV virion in saline, significant levels of anti-gp51 antibodies were induced as shown both in Western blot and immunodiffusion analyses. In these animals, antibodies against gag product (p24) were not detected. On the other hand, the rabbits inoculated with wild-type vaccinia virus and boosted similarly three times with the BLV virion in saline did not induce detectable anti-gp51 antibodies at all. The present experiment revealed that the RVV possessed the capability to endow immunological memory without inducing apparent anti-gp51 antibody responses, meaning that the RVV activated helper T cells far more strongly than B cells. The applicability of the RVV to vaccine development is discussed.
In this study, 6 older and 10 younger Japanese men were exposed, while sitting, to 40 degrees C and 40% relative humidity for up to 130 min. All participants were heat unacclimatized. Physiological measurements included sweat responses, esophageal and skin temperatures, nonevaporative heat exchange, heart rate, cardiac output, blood pressure, forearm blood flow, and metabolic heat production. There was no significant difference in sweat rate or in onset of sweating between the older and younger men; however, esophageal temperature at the onset of sweating was greater in the older men. Changes in skin temperature, nonevaporative heat exchange, metabolic heat production, heart rate, and cardiac output were the same during heat exposure in both age groups. However, forearm blood flow before and after exposure to heat was significantly lower in the elderly group. These data suggest that the greater health risk posed to resting, yet healthy, aged men by hot environments is not a consequence of inadequate sweating but could be associated with retardation of the vasodilation reflex, which can prevent effective transfer of the body heat to its shell, thus resulting in greater heat storage.
Monoclonal antibodies were used to examine the immunohistochemical expression of pepsinogens I and II in 31 early and 76 advanced gastric cancers. Of the 107 carcinomas studied, 19 contained pepsinogen II and only 3, found exclusively in pepsinogen II-positive cases, contained pepsinogen I. Gastric cancer produces pepsinogen II more frequently than pepsinogen I, and production of the latter is significantly associated with the former. Histologically, there were 54 intestinal-type and 53 diffuse-type cancers. The former produced pepsinogen II more frequently than the latter. In the diffuse type, the four pepsinogen II-positive cases were found exclusively in females. Although the pepsinogen expression was independent of the macroscopic features in advanced gastric cancer, it was found that the protruded-type early gastric cancer produced pepsinogen II more frequently than the depressed type. Incidences of pepsinogen positivity were not different between early and advanced gastric cancers or between cancers with or without lymph node metastasis, suggesting that production of pepsinogen is independent of tumor growth.
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The present investigation was undertaken to test the hypothesis that a circadian variation in the atrial natriuretic factor (ANF) response is responsible for the nocturnal inhibition of renal responses to head-out immersion (HOI). Plasma ANF responses to a 3-h HOI (water temperature 34.5 +/- 0.5 degrees C) were studied during day (1000-1300) and night (2400-0300) in six hydropenic male human subjects. In agreement with the previous observations, the renal responses, especially the diuresis, to HOI were attenuated at night compared with the day; furthermore, plasma renin activity decreased to the same low level during HOI at both day and night. Plasma ANF during time control periods was 30-40 pg/ml without showing any circadian variation. Moreover, plasma ANF showed a similar twofold increase within 1 h of HOI and was maintained at this elevated level throughout the 3-h HOI period in both the daytime and the nighttime series. On termination of HOI, plasma ANF decreased linearly to the pre-HOI level within 1 h. Hematocrit during time control periods was higher during the day compared with the night (P less than 0.05). Although HOI appears to induce a transient increase in plasma volume (as indicated by decreases in hematocrit) during the 1 h of HOI, the magnitude of the decrease in the latter parameters was not different between day and night. It is concluded that nocturnal inhibition of renal responses to HOI cannot be fully accounted for by circadian differences in the ANF and fluid shift response to HOI.
After overnight food and fluid restriction, seven healthy old (62-74 yr) and eight young (21-28 yr) men were examined before, during, and after 3-h head-out immersion (HOI) in thermoneutral water (34.5 +/- 0.5 degrees C). On separate days, all subjects remained seated in air for 5 h to obtain the time control data. Although HOI induced a reversible increase in urine flow in all subjects, the response was faster and greater in magnitude in the elderly than in the young. Na excretion and osmolal clearance also followed a response pattern identical to that of urine flow; thus the HOI-induced diuresis was entirely osmotic. Endogenous creatinine clearance increased in the elderly at 2 h of HOI, suggesting an age-related modification in kidney hemodynamics. Although there was virtually the same cephalad blood shift (measured by impedance cardiography), mean arterial pressure significantly increased (P less than 0.05) during HOI in the elderly, which also indicated a different response of peripheral circulation to HOI in the elderly. Control level of plasma atrial natriuretic factor (ANF) was nearly twofold greater in the elderly compared with the young. The HOI induced a nearly fourfold increase in ANF in the elderly, whereas that for the young was threefold. Both plasma aldosterone and ADH responses to HOI were attenuated in the elderly compared with the young, which had no correlation with urine flow or Na excretion. It is concluded that the elderly release more ANF at a given cephalad volume expansion compared with the young, but the vasodilative reaction to ANF was attenuated in the elderly.
Hypoxia alters the relationship of aldosterone secretion to plasma renin activity. The potential role plasma electrolytes play in this modification is not clear. This study analyzed the interrelationships among renin, aldosterone, vasopressin (ADH), and plasma electrolytes during 96 h of normobaric hypoxia. Eight ewes were exposed, in discrete experiments, to hypocapnic hypoxia [arterial O2 tension (PaO2) 37-42 mmHg, arterial CO2 tension (PaCO2) 26-28 mmHg] and eucapnic hypoxia (PaO2 40-43 mmHg, PaCO2 28-31 mmHg) by N2 dilution in an environmental chamber. Urine output (24 h) was measured, and arterial plasma samples were collected during the normoxic control period and at 24-h intervals of hypoxia. Plasma Na+, K+, renin, and ADH levels did not change from the normoxic values during either hypocapnic or eucapnic hypoxia. However, urinary aldosterone excretion [critical significance (alpha) less than 0.046] and K+ excretion (alpha less than 0.046) decreased markedly during each type of hypoxia. All sheep developed a pronounced negative K+ balance by 96 h of hypoxia. These data suggest that plasma K+ concentration is preserved by movement of K+ out of the intracellular compartment; this change in K+ distribution may inhibit aldosterone secretion during hypoxia.
The present work was undertaken to determine the critical water temperature (Tcw), defined as the lowest water temperature a subject can tolerate at rest for 3 h without shivering, of wet-suited subjects during water immersion at different ambient pressures. Nine healthy males wearing neoprene wet suits (5 mm thick) were subjected to immersion to the neck in water at 1, 2, and 2.5 ATA while resting for 3 h. Continuous measurements of esophageal (T(es)) and skin (Tsk) temperatures and heat loss from the skin (Htissue) and wet suits (Hsuit) were recorded. Insulation of the tissue (Itissue), wet suits (Isuit), and overall total (Itotal) were calculated from the temperature gradient and the heat loss. The Tcw increased curvilinearly as the pressure increased, whereas the metabolic heat production during rest and immersion was identical over the range of pressure tested. During the 3rd h of immersion, Tes was identical under all atmospheric pressures; however, Tsk was significantly higher (P less than 0.05) at 2 and 2.5 ATA compared with 1 ATA. A 42 (P less than 0.001) and 50% (P less than 0.001), reduction in Isuit from the 1 ATA value was detected at 2 and 2.5 ATA, respectively. However, overall mean Itissue was maximal and independent of the pressure during immersion at Tcw. The Itotal was also significantly smaller in 2 and 2.5 ATA compared with 1 ATA. The Itissue provided most insulation in the extremities, such as the hand and foot, and the contribution of Isuit in these body parts was relatively small. On the other hand, Itissue of the trunk areas, such as the chest, back, and thigh, was not high compared with the extremities, and Isuit played a major role in the protection of heat drain from these body parts.
The present work was undertaken to determine the effect of atmospheric pressure [ranging from a high altitude of 4,300 m above sea level or 0.6 atmospheres absolute (ATA) to depths of 10 m deep or 2 ATA] on the critical water temperature (Tcw), defined as the lowest water temperature a subject can tolerate at rest for 2 h without shivering, of the unprotected subject during water immersion. Nine healthy males wearing only shorts were subjected to immersion to the neck in water at 0.6, 1, and 2 ATA while resting for 2 h. Continuous measurements included esophageal (Tes) and skin (Tsk) temperatures, direct heat loss from the skin (Htissue), and insulation of the tissue (Itissue). The Tcw was significantly higher at 0.6 ATA than 1 and 2 ATA: however, Tcw at 1 ATA was identical to that at 2 ATA. The metabolic heat production remained unchanged among the pressures. During the 2-h immersion in Tcw, Tes was identical among all atmospheric pressures: however, Tsk was significantly higher (P less than 0.05) at 0.6 ATA and was identical between 1 and 2 ATA. The overall mean Itissue was near maximal during immersion in Tcw in each pressure, and no difference was detected among the pressures. However, Itissue at the acral extremities (arm, hand, and foot) decreased significantly at 0.6 ATA, and subsequently heat loss from these parts was increased, which elevated an extremity-to-trunk heat loss ratio to 1.4 at 0.6 ATA from 1.1 at 1 and 2 ATA.(ABSTRACT TRUNCATED AT 250 WORDS)
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Crystals of the hydrophilic, catalytic domain (30 kDa) of pig liver NADH-cytochrome b5 reductase solubilized by the protease (cathepsin D) have been grown in a solution of polyethylene glycol by the vapor-diffusion procedure. The crystals belong to the orthorhombic system, space group P2(1)2(1)2(1) with unit-cell dimensions of a = 87.1, b = 73.2, and c = 49.0 A. The asymmetric unit contains one molecule of the enzyme. The x-ray diffraction patterns extend to 2.0-A resolution. On the other hand, the intact enzyme (35 kDa) containing the hydrophobic membrane-binding domain solubilized by the detergent (Triton N-101) has been crystallized also from the polyethylene glycol solution. The crystals are needle-shaped and still too small for x-ray diffraction study.
Pathology of the thyroid gland tissue was characterized in patients with Triiodothyronine (T3)-predominant Graves' disease who had normal levels of serum T4 but increased levels of serum T3 during antithyroid drug therapy. In order to compare this group of patients with an usual type of Graves' patients, age, sex, dietary intake of iodide, duration of antithyroid therapy and the dose of thionamide drugs were matched between the two groups of patients. Thyroid tissue was obtained from subtotal thyroidectomy. In examining the histology of the thyroid gland, integration eye piece plate II with regularly arranged 100 lattice points was set on eye lens of a microscope. The number of crossing points which were projected on each 4 histological elements was counted in randomly selected 10 fields of vision in each patient's thyroid. Assuming that the every histological element is arranged in a random manner, errors of each visual field by this method would be less than 12%. In consequence, the significant difference was demonstrated in the weight of subtotally resected thyroid and the ratio of each histological element except interstitial tissue occupied in the total thyroid tissue between T3-predominant Graves' disease and control Graves' disease. The volume composition of the epithelial cells and vacuoles in patients with T3-predominant Graves' disease was significantly greater than that of patients with control Graves' disease (24.7 +/- 10.6 vs 14.4 +/- 6.5%, 5.9 +/- 3.9 vs 2.0 +/- 1.0%, Mean +/- SD, respectively, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)