The occupational meaning of smell

The sense of smell has its meaning for a successful performance of certain occupations. It has further a protective meaning. The acuity of smell often changes for different reasons. The prolonged or repeated smelling is combined with the process of smell adaptation, fatigue and habituation. They diminish the flavour sensations and increase the risk of work accidents. Some chemical compounds are characterized by a quick and high adaptation. The occupational changes of smell can be peripheral or central. The qualitative changes of the smell perception are numerous, but they have little sense in industrial hygiene. The hypersensibilisation can be temporal or lasting, where a change of profession is sometimes inevitable. The values of smell thresholds (detection, recognition, distinction) of 25 substances are given. The sensitivity of smell is greater at the smell threshold concentrations. The smell thresholds are put among the main basic properties of chemical compounds which decide about the values of MAC and about the possibilities of their passing over. 68 substances ranged according to their basic characteristics in three groups were studied. There was statistical dependence between the molecular weight, the boiling point, smell thresholds of detection and recognition. In two groups of matters there was a dependence between the threshold of irritation and the smell threshold of recognition and distinction. The regression was linear with the majority of dependencies.     

Relationship between an offensive smell given off from human foot and Staphylococcus epidermidis

The bacteria isolated from foot skins of 17 volunteers by the swab sampling method were mostly gram-positive cocci, which were identified as Staphylococcus epidermidis by the ID-kit SP-18 (Nissui Co., Ltd). After incubation of S. epidermidis on agar plates containing oleic acid and Tween 80 for 24 h at 35 C, the smell noticed was similar to an offensive smell of human pes. However, under the same conditions, the smell of another staphylococcal species was different from that of S. epidermidis. Except for the staphylococcal species, the colonies isolated from the skins were mostly those of yeast (unidentified) and gave off no offensive smell. From these results, it was considered that the smell of human pes might be given off by S. epidermidis, and if this species is inhibited, the smell would also be inhibited. A selective bactericide for gram-positive bacteria, which is a lotion containing deoxycholic acid, was applied to the feet of the 17 volunteers. The experiments showed that the application obviously decreased the counts of colonies of S. epidermidis and inhibited the smell as compared with controls.     

A longitudinal descriptive study of self-reported abnormal smell and taste perception in pregnant women

Self-reported abnormal sensitivity, qualitative distortions and phantom sensations with respect to smell and taste was assessed with a longitudinal design, based on questions referring to gestational weeks 13-16 and 31-34 of pregnancy in comparison with 9-12 weeks post partum and with non-pregnant women with corresponding time durations and intervals. The results show that abnormal smell and/or taste perception was reported by 76% of the pregnant women, typically believed to be caused by their pregnancy. Increased smell sensitivity was found to be very common at the early stage of pregnancy (67% of all pregnant respondents) and occasionally accompanied by qualitative smell distortions (17%) and phantom smells (14%). The smell abnormalities were less common at the late pregnancy stage and almost absent post partum. Abnormal taste sensitivity was fairly commonly reported (26%), often described as increased bitter sensitivity and decreased salt sensitivity. These results, suggesting that abnormal smell and/or taste perception is experienced by a large majority of pregnant women, imply that further research is needed to understand to what extent these chemosensory changes may underlie food aversions and craving with implications for food intake during pregnancy.     

Effect of a combination of mild-temperature hyperthermia and nicotinamide on the radiation response of experimental tumors

Ogawa, A., Griffin, R. J. and Song, C. W. Effect of a Combination of Mild-Temperature Hyperthermia and Nicotinamide on the Radiation Response of Experimental Tumors. The effect of mild-temperature hyperthermia and nicotinamide individually or combined on tumor radiosensitivity was investigated with SCK tumors grown s.c. in the right hind limbs of A/J mice. An i.p. injection of nicotinamide at 50-250 mg/kg slightly enhanced the cell killing caused by 10-20 Gy of ionizing radiation as determined by the in vivo/in vitro tumor excision assay. Treatment of tumors with mild-temperature hyperthermia at 41.5 degrees C for 60 min prior to tumor irradiation was significantly more effective than nicotinamide and the combination of nicotinamide and hyperthermia was far more effective than nicotinamide or hyperthermia alone in enhancing radiation-induced cell killing. Radiation-induced tumor growth delay was enhanced by a factor of 1.2 by 50 mg/kg nicotinamide, 2.1 by hyperthermia, and 3.6 by the combination of nicotinamide and hyperthermia. Taking these results and those of our previous studies together, we conclude that mild-temperature hyperthermia increases tumor blood flow and oxygenation and that combining mild-temperature hyperthermia and nicotinamide is more effective than either of these alone in increasing tumor radiosensitivity.     

A polymorphism of the ability to smell urinary metabolites of asparagus.

The urinary excretion of (an) odorous substance(s) after eating asparagus is not an inborn error of metabolism as has been supposed. The detection of the odour constitutes a specific smell hypersensitivity. Those who could smell the odour in their own urine could all smell it in the urine of anyone who had eaten asparagus, whether or not that person was able to smell it himself. Thresholds for detecting the odour appeared to be bimodal in distribution, with 10% of 307 subjects tested able to smell it at high dilutions, suggesting a genetically determined specific hypersensitivity.     

The response of previously irradiated skin to combinations of X radiation and ultrasound-induced hyperthermia

Areas of skin approximately 1.5 cm in diameter on the legs of mice were made hyperthermic (30 min at 42.7 degrees C) by exposure to an ultrasound beam (780 kHz), a single dose of X irradiation (2000 rad), or a combination of these treatments. After 35 days, when the acute reaction had reached a steady state, the same tissue was given a second treatment by either hyperthermia, irradiation, or a combination of hyperthermia and irradiation. When the first treatment was irradiation and the second treatment was either irradiation or a combination of hyperthermia and irradiation, the acute skin reactions were similar to those of skin not previously irradiated, indicating a large proportion of recovery from the first irradiation. When irradiation was the first treatment, a comparison of second treatments by hyperthermia plus irradiation with irradiation alone showed a thermal enhancement of 1.45. When the first treatment was hyperthermia plus irradiation, a comparison of second treatments by hyperthermia plus irradiation with irradiation also showed an enhancement factor of 1.45 for the combined treatment.     

Mechanisms of hyperthermia-induced depression of GABAergic synaptic transmission in the immature rat hippocampus

Clinical observations and experimental studies have shown that hyperthermia can provoke febrile seizures, which are the most common type of pathological brain activity in children. We previously demonstrated that hyperthermia produced a depression of GABAergic neurotransmission in the hippocampus of immature rats in vitro. To investigate the possible mechanisms through which hyperthermia may modulate GABAergic neurotransmission in the hippocampus, whole-cell voltage clamp recordings were performed on CA1 pyramidal neurons in the immature rat brain slices. We found that hyperthermia (38.4-40 degrees C) when compared with baseline temperature of 32 degrees C reduced the frequency of both spontaneous inhibitory post-synaptic currents (sIPSCs) and miniature IPSCs (mIPSCs). Also, hyperthermia decreased the amplitudes of mIPSCs and reduced the mIPSC decay time constants and charge transfer. Non-stationary noise analysis of mIPSCs suggested that the number of open post-synaptic receptors but not single channel conductance was reduced during hyperthermia. Activation of adenylyl cyclase with forskolin prevented, whereas protein kinase A inhibitor N-(2-[p-bromocinnamylamino]ethyl)-5-isoquinolinesulfonamide potentiated, the hyperthermia (40 degrees C)-induced depression of evoked IPSCs (evIPSCs). But protein kinase C activator phorbol 12, 13-dibutyrate (PDBu) did not significantly affect this depression of evIPSCs induced by hyperthermia. Furthermore, hyperthermia-induced depression of evIPSCs was attenuated by 4-aminopyridine, but not by BaCl(2). These results suggest that hyperthermia reduces GABA release from pre-synaptic terminals, in part by blocking the adenylyl cyclase-protein kinase A signaling pathway and activating pre-synaptic 4-aminopyridine-sensitive K(+) channels. Also, the changes in amplitude and decay time constant of the mIPSCs may suggest that hyperthermia also decreases post-synaptic GABA(A) receptor function.     

Effect of hyperthermia on the antitumor actions of interferons.

Hyperthermia treatment has been shown to enhance the in vitro antiproliferative effects of IFN-alpha, IFN-beta, and IFN-gamma, with IFN-gamma being more strongly enhanced than IFN-alpha. The comparative effects of hyperthermia on the in vivo antitumor activities of IFN-alpha and IFN-gamma were evaluated in the murine system using both subcutaneous and intraperitoneal B16 melanoma tumor model systems. Heat-induced whole body hyperthermia, resulting in a 2 degree C rise in body temperature, was administered by incubating the mice for 8 hours in a dry incubator at 37.1 degrees C. Whole body hyperthermia was found to enhance the antitumor activity of IFN-alpha by approximately 1.0 fold and 1.2 fold for the subcutaneous and intraperitoneal tumor models, respectively. This represented an additive effect of hyperthermia and IFN-alpha. Hyperthermia was found to enhance the antitumor activity of IFN-gamma by approximately 2.9 fold and 2.2 fold for the subcutaneous and intraperitoneal tumor models, respectively. This represented a synergistic effect of hyperthermia and IFN-gamma. The results of this in vivo study confirm and extend the in vitro observation that hyperthermia more strongly enhances the antitumor action of IFN-gamma than IFN-alpha. These results may have clinical importance because they suggest that hyperthermia may be used in combination with IFN-gamma to provide a synergistically enhanced antitumor action.     

Development of a smell identification test using a novel stick-type odor presentation kit

The odor identification is strongly influenced by the social and cultural factors; therefore, the odorants used in a smell identification test should be familiar to the test population. In addition, the device used in the test is desired to be simply handled and retain odor quality over time. We developed a novel stick-type odor presentation kit that consists of microcapsules of odorant incorporated into stable cream and the smell identification test using it. Thirteen odorants were selected to be familiar to the test population. In the test, we used two identification methods: one was a modified forced-choice paradigm with "detectable but not recognizable" and "no smell detected" added as choices and the other was a two-step identification paradigm where the participant first selected one of eight odor categories and then chose the specific odor name from the selected category. We verified the performance of the odor stick and the test by stability, using a test-retest paradigm, comparing this test with another smell test, and testing Japanese people from a range of age groups. We conclude that this kit is a useful odor presentation device, and the test using it works effectively as a smell identification test.     

无腥味大豆种质创新与利用

大豆是植物油和植物蛋白的主要来源,但大豆蛋白中含有3种结构不同的脂肪氧化酶同功酶,是产生豆腥味的根源,使大豆利用及加工受到限制。从1994年开始我们进行大豆脂氧酶缺失基因的转育与种质创新研究,目前获得了一批综合农艺性状优良的低腥味材料,其中绥无腥豆1号已于2002年3月通过黑龙江省农作物品种审定委员会审定,并开始应用于生产和加工领域。     

Effect of hyperthermia on NF-kappaB binding activity in cerulein-induced acute pancreatitis

Although the pancreatic heat shock response has already been reported to confer protective effects during experimental pancreatitis, the mechanism of action remains unknown. We investigated the effects of hyperthermia in cerulein-induced pancreatitis. Heat shock protein 70 (HSP70) expression in rats was induced by a 20-min period of water immersion (42 degrees C). The severity of pancreatitis as well as the pancreatic expression of cytokines, nuclear factor-kappaB (NF-kappaB), and inhibitory factor kappaB-alpha (IkappaB-alpha) were evaluated in the presence and absence of hyperthermia. We found that hyperthermia resulted in time-dependent expression of HSP70 within the pancreas associated with a reduction in the severity of acute pancreatitis. Tumor necrosis factor-alpha and intercellular adhesion molecule-1 expression was significantly reduced in the presence of hyperthermia. Moreover, NF-kappaB activity was delayed in the presence of hyperthermia whereas IkappaB-alpha was stabilized in the cytoplasm. These results suggest that hyperthermia decreases the severity of cerulein-induced pancreatitis by decreasing cytokine expression in the pancreas through the modulation of NF-kappaB activity.     

Enhanced cytotoxicity and suppression of glucose transport rate by combined treatment of recombinant human tumour necrosis factor-alpha and hyperthermia on L929 cells.

Combined treatment with human recombinant TNF-alpha (rhTNF-alpha) and hyperthermia at 43 degrees C arrested the growth of mouse fibrosarcoma L929 cells in vitro. The cytotoxic effect was enhanced in combined treatment compared with that following administration of rhTNF-alpha or hyperthermia alone. When the cells were subjected to hyperthermia at 43 degrees C for 3 hours and then incubated with 0.4 ng/ml rhTNF-alpha at 37 degrees C for 24 hours, a statistically significant 65% decrease in the rate of cellular glucose uptake was observed. This suppressive effect was synergistic in terms of effect achieved by rhTNF-alpha or hyperthermia individually. Since the growth of tumour cells depends mainly on catabolism of glucose, our findings indicate that one manner by which combined rhTNF-alpha and hyperthermia treatment inhibits L929 cell growth may be by reducing the supply of glucose to the cells.     

大壁虎与嗅觉相关的学习记忆

壁虎科动物鼻腔较大,化学感觉系统发达,类似于对化学信息敏感的舌端游离的蜥蜴目动物（Malan,1946),并且嗅黏膜面积很大,感觉器神经元多,嗅神经系统十分完善（Gabe and Saint,1976).     

Effects of acute hyperthermia on the carotid baroreflex control of heart rate in humans

 The purpose of this study was to examine the effect of hyperthermia on the carotid baroreceptor-cardiac reflexes in humans. Nine healthy males underwent acute hyperthermia (esophageal temperature ∼38.0° C) produced by hot water-perfused suits. Beat-to-beat heart rate (HR) responses were determined during positive and negative R-wave-triggered neck pressure steps from +40 to −65 mm Hg during normothermia and hyperthermia. The carotid baroreceptor-cardiac reflex sensitivity was evaluated from the maximum slope of the HR response to changes in carotid distending pressure. Buffering capacity of the HR response to carotid distending pressure was evaluated in % from a reference point calculated as (HR at 0 mm Hg neck pressure−minimum HR)/HR range ×100. An upward shift of the curve was evident in hyperthermia because HR increased from 57.7±2.4 beats/min in normothermia to 88.7±4.1 beats/min in hyperthermia (P<0.05) without changes in mean arterial pressure. The maximum slope of the curve in hyperthermia was similar to that in normothermia. The reference point was increased (P<0.05) during hyperthermia. These results suggest that the sensitivity of the carotid baroreflex of HR remains unchanged in hyperthermia. However, the capacity for tachycardia response to rapid onset of hypotension is reduced and the capacity for bradycardia response to sudden hypertension is increased during acute hyperthermia. Received: 14 October 1996 /Revised: 16 January 1997 / Accepted: 21 January 1997     

Differential effects of hyperthermia on human leukocyte production of interferon-alpha and interferon-gamma

Hyperthermia is being used clinically in the treatment of neoplasms. However, there are insufficient data regarding effects of hyperthermia on leukocyte functions potentially important in antitumor immunity. In order to provide such data, human mononuclear leukocytes were exposed to moderate (40.7 degrees C) and marked (42.7 degrees C) hyperthermia for 2 hr. Leukocyte viability, measured by dye exclusion, was not altered by such exposures. Exposure of the cells to moderate hyperthermia did not alter leukocyte production of interferon-alpha in response to influenza virus or interferon-gamma in response to the mitogen phytohemagglutinin. Exposure of the cells to marked hyperthermia significantly depressed production of interferon-alpha. In contrast, production of interferon-gamma was not altered by exposure of the leukocytes to marked hyperthermia. Many studies support a role for interferons (alpha as well as gamma) in antitumor immunity. The current and other data suggest that marked hyperthermia in cancer therapy should be applied locally whenever possible, rather than to the whole body, in order to limit adverse effects on immunity. The data suggest further that interferon-gamma may be a heat shock (stress) protein for human leukocytes.     

Hyperthermia engages the intrinsic apoptotic pathway by enhancing upstream caspase activation to overcome apoptotic resistance in MCF-7 breast adenocarcinoma cells

Febrile hyperthermia enhanced TNF-stimulated apoptosis of MCF-7 cells and overcame resistance in a TNF-resistant, MCF-7 variant (3E9), increasing their TNF-sensitivity by 10- and 100-fold, respectively. In either cell line, the hyperthermic potentiation was attributable to increased apoptosis that was totally quenched by caspase inhibition. In MCF-7 cells, hyperthermic potentiation of apoptosis was associated with sustained activation of upstream caspases in response to TNF and more prominent engagement of the intrinsic apoptotic pathway. Apoptotic enhancement by hyperthermia was primarily mediated by caspase-8 activation, as the specific inhibitor, Z-IETD, blocked cell death, whereas direct engagement of the intrinsic apoptotic pathway (with doxorubicin) was not affected. In 3E9 cells, hyperthermia alone induced activation of caspase-8, and was further enhanced by TNF. In 3E9 cells, hyperthermia caused TNF-dependent loss of mitochondrial membrane potential and activation of capspase-9 that was initiated and dependent on upstream caspases. MCF-7 and 3E9 cells were equally sensitive to exogenous C(6)-ceramide, but mass spectroscopic analysis of ceramide species indicated that total ceramide content was not enhanced by TNF and/or hyperthermia treatment, and that the combination of TNF and hyperthermia caused only modest elevation of one species (dihydro-palmitoyl ceramide). We conclude that febrile hyperthermia potentiates apoptosis of MCF-7 cells and overcomes TNF-resistance by sustained activation of caspase-8 and engagement of the intrinsic pathway that is independent of ceramide flux. This report provides the first evidence for regulation of caspase-dependent apoptosis by febrile hyperthermia.     

Contributions of Smell and taste to overall intensity

The integration of olfaction and gustation in producing thesensation of flavor was studied using an almond extract stimuluspresented with the Two-Module Delivery System. Almond in themouth was found to influence the scaling of smell. The datasugest that this background effect is due to the diffusion ofairborne molecules from the oral cavity to the olfactory receptorsarea. At least under some stimulation conditons, almond vaporin the nose was shown to afect the scaling of taste. When scalingoverall intensity, subjects apparently added together the sensationsof smell and taste to produce the sensation of overall intensity.However, for all combinations of odorants and tastants, theestimate of overall intensity was less than the sum of the estimateof the smell and the estimate of the taste. The data furthersuggest that when estimating the overall intensity, the magnitudeassigned to the olfactory or gustatory sensations was less thanthat which have been assigned when estimating just smell ortaste.     

Modification of radiation damage in the canine kidney by hyperthermia: a histologic and functional study

The purpose of this study was to evaluate the effect of hyperthermia on the histologic and functional response of the canine kidney, a late-responding normal tissue, to irradiation. Both kidneys were irradiated. Radiation was delivered in single doses of 0, 10, or 15 Gy. Whole-body hyperthermia was used to produce renal kidney temperatures approximating 42.0 degrees C for 60 min. Thirty-six beagles were placed randomly in the following six treatment groups: control, whole-body hyperthermia alone, 10 Gy alone, 10 Gy + whole-body hyperthermia, 15 Gy alone, and 15 Gy + whole-body hyperthermia. Renal histologic and functional changes were assessed at 1 to 9 months after therapy. No changes were seen in glomerular filtration rate or renal tissue volumes in control or hyperthermia alone groups. Renal vascular and glomerular volumes were not affected significantly by any combination of hyperthermia and/or radiation. In all groups receiving radiation, glomerular filtration rate decreased, percentage renal tubular volume decreased, and interstitial volume increased significantly after therapy. The magnitude of these changes in the functional and histologic response of the kidney and the latent period before expression of this damage were dependent on radiation dose. However, hyperthermia did not modify expression of radiation damage in the kidney based on glomerular filtration rate and histologic quantification of renal tissue components.     

Influence of hyperthermia and gamma radiation on ADP-ribosyl transferase, NAD+, and ATP pools in human mononuclear leukocytes

Effects of hyperthermia (42.5 degrees C) and gamma radiation (30 Gy) on ADP-ribosyl transferase, NAD+, and ATP pools in human mononuclear leukocytes have been investigated. It was found that the gamma-ray activation level of the enzyme was not influenced by this hyperthermia for 45 min. Following deprivation of ATP synthesis by 2,4-dinitrophenol, an uncoupler of the oxidative phosphorylation, and omitting glucose from the culture medium, the NAD+ pool was reduced to about 60% of control value. The potentiation of ATP production by exogenously supplied adenosine was reduced after a combined treatment of the cells with hyperthermia and gamma radiation. Mitochondrial and endoplasmic changes within the mononuclear leukocytes were also observed. Based on these findings a model for the hyperthermia effect is proposed.     

Histone Deacetylase Inhibitors Sensitize Lung Cancer Cells to Hyperthermia: Involvement of Ku70/SirT-1 in Thermo-Protection

This study describes the sensitization mechanism to thermal stress by histone deacetylase inhibitors (HDACIs) in lung cancer cells and shows that Ku70, based on its acetylation status, mediates the protection of lung cancer from hyperthermia (42.5°C, 1-6 hrs). Ku70 regulates apoptosis by sequestering pro-apoptotic Bax. However, its role in thermal stress is not fully understood. The findings showed that, pre-treating lung cancer cells with HDACIs, nicotinamide (NM) or Trichostatin A (TsA) or both significantly enhanced hyperthermia-induced Bax-dependent apoptosis in PC-10 cells. We found that hyperthermia induces SirT-1, Sirtuin, upregulation but not HDAC6 or SirT-3, therefore transfection with dominant negative SirT-1 (Y/H) also eliminated the protection and resulted in more cell death by hyperthermia, in H1299 cells through Bax activation. Hyperthermia alone primed lung cancer cells to apoptosis without prominent death. After hyperthermia Bax was upregulated, Bcl-2 was downregulated, the Bax/Bcl-2 ratio was inversed and Bax/Bcl-2 heterodimer was dissociated. Although hyperthermia did not affect total Ku70 expression level, it stimulated Ku70 deacetylation, which in turn could bind more Bax in the PC-10 cells. These findings suggest an escape mechanism from hyperthermia-induced Bax activation. To verify the role of Ku70 in this protection mechanism, Ku70 was silenced by siRNA. Ku70 silencing significantly sensitized the lung cancer cells to hyperthermia. The Ku70 KD cells underwent cytotoxic G1 arrest and caspase-dependant apoptosis when compared to scrambled transfectants which showed only G2/M cytostatic arrest in the cell lines investigated, suggesting an additional cell cycle-dependent, novel, role of Ku70 in protection from hyperthermia. Taken together, our data show a Ku70-dependent protection mechanism from hyperthermia. Targeting Ku70 and/or its acetylation during hyperthermia may represent a promising therapeutic approach for lung cancer.