Note on the activation of oxido-reductions by co-zymase.
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Biomedical subjects
Publications and source records attributed to R Nilsson.
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To investigate possible persistent nephrotoxic effects of trichloroethylene (TRI), a retrospective study was carried out on 39 workers exposed to high levels of TRI from 1956 to 1975. Total protein levels in urine, as well as serum and urine creatinine and serum urea were unchanged in comparison with the control. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) was applied to differentiate between tubular and/or glomerular dysfunction. Urinary excretion of alpha-1-microglobulin and glutathione transferase (GST) alpha, as markers of proximal tubular damage, were correlated with the SDS-PAGE patterns of urinary proteins both in the TRI exposed and the control group. GST alpha was found in elevated concentrations in the urine of the TRI-exposed workers. No increase of urinary GST alpha was observed in the control group, even when alpha-1-microglobulin was elevated as a result of non-toxic damage. Both in the control and exposed groups, GST pi, a marker of distal tubular damage, was in the normal range. The results show that chronic exposure to high doses of TRI causes persistent changes to the proximal tubular system of the kidney and that GST alpha excretion into the urine is a marker well suited for quantitation of the extent of renal damage.
The distribution of alpha and pi class glutathione transferases in autopsy and biopsy samples of normal human tissues was investigated by immunohistochemistry. The class alpha glutathione transferases exhibited restricted distribution. Intensive staining was visible in all hepatocytes, in kidney proximal tubular cells, in the zona reticularis of adrenal cortex and in Leydig cells of testis. Staining of lesser intensity could also be observed in the gastrointestinal epithelium, exocrine pancreas and some bile and pancreas ducts. In colon and gall bladder only nuclei were stained, but in the other tissues both nuclei and cytoplasm contained alpha class glutathione transferases. Glutathione transferase pi exhibited a more general distribution and could be observed in epithelia of the respiratory, gastrointestinal and urinary tracts, in all endocrine cells investigated, and also in the exocrine glands of prostate, in smooth muscle, adipocytes, blood vessel endothelium and placenta. It was also visible in the Schwann cells of peripheral nerves and in the choroid plexus. In gall bladder and colon only nuclei were stained, while in the intrahepatic bile ducts only cytoplasm was stained. All other positive cells exhibited glutathione transferase pi in both nuclei and cytoplasm.
Endoluminal ultrasonography of the esophagus offers a possibility to study the esophageal wall, even in pathological disorders with narrow lumina such as benign or malignant strictures, by using 2.7-mm-wide probes. In order to evaluate the normal variations in size of the esophageal wall components, 10 volunteers and 10 deceased humans without upper gastrointestinal disease were studied with a 2.7-mm-wide endoluminal ultrasonic probe. A comparison with a histopathological technique was also performed. The results indicated a good correlation between the volunteers and the deceased in using endoluminal ultrasonography. In contrast a discrepancy was noted between the measurements made by ultrasonography and histopathology.
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Recently, considerable attention has been focused on certain environmental contaminants--"endocrine disruptors"--of industrial origin that may mimic the action of sex hormones. Natural compounds and their effects on other types of hormonal activity (eg, on adrenal or thyroid function) have for some reason not provoked similar attention. As exemplified by tributyltin and certain bioaccumulating chlorinated compounds, available evidence indicates that "endocrine disruption" caused by xenobiotics is primarily an ecotoxicologic problem. In mammals, certain phenylmethyl-substituted siloxanes have been found to be by far the most potent endocrine disrupters among various synthetic xenobiotics. On the other hand, it has not been possible to scientifically substantiate either certain alarming reports of powerful synergistic effects between chlorinated pesticides or the alleged adverse effects on the male reproductive tract in rodents (induced by alkylphenols and plasticizers at extremely low exposures). Whereas there is compelling evidence that estrogens in certain foods and herbal medicines can induce hormonal changes in women as well as overt toxicity in men, existing data are insufficient to support a causal relationship between exposure of the general human population to nonpharmaceutical industrial chemicals and adverse effects operating via the endocrine system. Moreover, in terms of magnitude and extent, all such exposures to so-called endocrine disruptors are dwarfed by the extensive use of oral contraceptives and estrogens for treatment of menopausal and postmenopausal disorders. Also, the exposure to hormonally active xenobiotics is virtually insignificant when compared with the intake of the phytoestrogens that are present in food and beverages, and it is even more insignificant when compared with certain herbal potions used in "alternative medicine." Furthermore, while there has been much concern about negligible exposures to xenobiotics with weak hormonelike activities, the potent endocrine disruptor licorice is freely given to children. Long-term exposure to this substance induces severe toxic symptoms of mineral corticoid hormone imbalance. Although exposures to xenobiotics and many natural compounds occur by identical routes of administration and may contribute to the same toxicological end point, they are, regrettably, judged by completely different standards. As is the case with all other chemicals, rational risk assessment and risk management of man-made and natural endocrine modulators must be based on the mode of action and dose-response relationships. Such end points as the induction of reproductive developmental effects, cancer, etc, relating to actual exposures must also be taken into consideration.
Among 1 257 patients subjected to liver-spleen (RES) scintigraphy and radionuclide angiography (RNA), there were 13 cases of histologically confirmed hepatocellular carcinoma (1%). All 13 patients had scintigraphic findings indicating cirrhosis. Histologically, cirrhosis was present in only 9 out of 11 cases in which liver parenchyma was available for examination. One patient had hemochromatosis without evidence of cirrhosis. In 11 cases, the tumor was clearly demonstrated as a defect in the static scintigram. However, in 2 cases with cirrhosis and poorly differentiated hepatocellular carcinoma, the tumor nodules were hardly discernible. In RNA, the tumor displayed high activity in the arterial phase and decreasing activity during the portal phase, ending up as a defect. At RNA, the lesion was clearly outlined in 12 cases, including the 2 patients in whom the scintigraphic findings were inconclusive; in one case with severe cirrhosis and a well differentiated hepatocellular carcinoma, the tumor was barely detectable. We conclude that a combination of RNA and scintigraphy is a valuable screening which usually provides a correct diagnosis in hepatocellular carcinoma.
The prevalence of sexual behaviours was estimated from a survey of 3854 Australian secondary school students. Self-reported prevalence of intercourse increased from 9.9% (age 13 years or less) to 23.9% (age 15) and 51.2% at age 17 and over. Among 932 sexually experienced youth in the final 3 years of secondary school, 26% of males and 18% of females reported having 3 or more partners in the previous year; 89.4% had used a condom at least once, with males (71.8%) reporting more last occasion condom use than females (53.4%). 'Last occasion' and 'usual', but not lifetime, condom use was significantly lower among older respondents. Although nearly 90% of females in each of 3 age groups reported lifetime condom use, just 27.6% of female students aged 17 or more reported that condoms were always used during intercourse. The decline with age, noted in research with adults and older adolescents, may begin in the middle teens.
A 500 Hz pure tone is presented binaurally with earphones. The tone is adjusted to give a midline impression at confortable loudness level. An electronic variable time delay line unit and a generator for randomizing the shift of the phase lag of the signal to the right or to the left ear, respectively, are used. By shortening the time delay the threshold of the recognition of the phase difference is reached. At every test sequence the tone is first presented in the center of the head without delay and then with delay. The patient runs the test by indicating in which ear the tone is heard. The phase difference is thus gradually reduced from 500 musec down to a threshold value of about 48 musec equal on right and left ears in normal-hearing subjects. The results of phase audiometry on subjects with normal hearing and with different types of hearing losses are in good agreement with the results of sound localization tests in free field. Phase audiometry seems to be of especial value in diagnosing retrocochlear lesions.
Normal hearing subjects were monaurally exposed to 30 min of tape recorded shipyard noise (97 dB (A)) which is characterized by a variable temporal structure. The stapedius muscle activity was continuously recorded in the opposite ear as a change of the ear's acoustic impedance. The reflex function was, in addition, assessed as stimulus-response curves obtained before and, at various times after, exposure. A slight reflex fatigue was observed, together with a parallel shift of the stimulus-response curve (average 4 dB). The recovery was slow and not complete even 10 min after the end of the exposure. The individual variability was large. For 5 of the subjects the exposure was repeated at a later session and the individual degree of fatigue was found to be largely producible. The present results suggest that the stapedius reflex might play a role in the clinical picture of noise induced hearing loss.
The depression of the stapedius reflex after a whole workday in industrial noise was studied in 11 normal-hearing employees at a shipbuilding yard. The reflex activity was assessed with simultaneous bilateral recordings of impedance change induced by stimulation with 2 000 and 500 Hz tones. One ear was exposed for approximately 7 hours in the plant, the other one was protected. The dose was measured individually at 89--103 dB(A) equivalent level. Utilization of bilateral recordings together with a unilateral exposure enabled an analysis based on the whole stimulus response curves. The results show that the reflex is depressed on the average 4 dB at 2 000 Hz 10 min after end of workday. By extrapolation the stapedius reflex was estimated to be depressed less than 10 dB at the end of the exposure. Since the stimulus-response curves are shifted in parallel, the contraction during the high-level components of the noise were largely unaffected. No evidence was found for creation of transtympanic pressure differences during noise exposure. It was concluded that the reflex fulfils one necessary condition for influencing the individual pattern of noise damage to the ear, fatigue resistance in the presence of long-term exposure to hazardous noise.
Shipyard noise is a variable noise which induces permanent threshold shift (PTS) in exposed workers. In humans, the stapedius reflex has been found to be very stable in this type of exposure. Temporary threshold shift (TTS) in the absence of stapedius reflex has been found to extend downwards through the speech-frequencies instead of showing a high frequency dip as when the stapedius reflex is normal. The features of PTS produced by the same type of noise was investigated in rabbits with and without functioning middle ear muscles. The auditory sensitivity was measured by auditory brain stem response (ABR) and by the stapedius reflex response. Middle ear muscle function was blocked by denervation of the stapedius muscle or by general anesthesia. With normal middle ear reflex very little PTS was found. When the muscles were inactivated during the noise exposure the PTS was very extensive and covered the mid frequency range. On the basis of previous findings in humans and the present animal study it is suggested that the features of the stapedius reflex should be considered both in assessment of individual susceptibility and design of optimal acoustic environments.
Iodinated epidermal growth factor was used to identify its specific receptor in 32 human colorectal carcinomas. The receptor was found in 25% of the tumors with values between 6.9 - 104.0 fmoles/mg DNA. Receptors for estrogen and progesterone were detected in 45 and 25% of the tumors respectively. No correlation was observed between short term survival and content of receptors for sex steroid hormones. Four of the 8 patients with detectable levels of epidermal growth factor receptor had experienced relapse.
The use of radiographic contrast media is occasionally accompanied by more or less serious adverse effects, evidently of complex etiology, following intravascular administration. Some of these reactions are suspected of having an allergic basis. The in vitro and in vivo formation of iodinated serum proteins following gamma irradiation in the presence of two commonly used radiographic contrast media is demonstrated. Non-toxic concentrations of ascorbate present during the irradiation is shown to prevent the formation of such iodo-proteins in vitro as well as in vivo. The amounts of potentially antigenic iodoprotein formed during radiographic procedures will certainly be very small, but this quantity may be sufficient to elicit a hypersensitivity reaction in cases when an individual has been previously sensitized to immunologically similar iodo-proteins, a mechanism that could account for certain rare and unpredictable reactions. The radiation induced formation of iodo-proteins may also serve as a model for the formation of iodine containing antigens mediated by a free radical mechanism, i.e. in the metabolism of iodinated compounds like erythrosine, a widely used colouring agent for certain foods.
Thirty cases of chronic recurrent multifocal osteomyelitis have been reported in the literature. A radiologic evaluation of thirty-one additional cases, 25 of whom also underwent bone scintigraphy, is presented. Bone biopsy specimens were obtained in 16 patients. Most lesions were located in the metaphyses of the long bones adjacent to the physis and had a characteristic, probably pathognomonic appearance. Extension into the epiphyses was rare. Lesions in the vertebral bodies, clavicle and pelvis had possibly a less specific radiographic appearance. Lesions in short tubular bones were non-specific. Bone scintigraphy had a practical value in evaluating the global distribution of lesions including asymptomatic lesions and lesions in the spine or pelvis, the latter being somewhat hard to detect with conventional radiography. All biopsies showed acute, subacute or chronic unspecific osteomyelitis, sometimes mixed in the same lesion. Staining for bacteria and fungi was negative.