Assembly of 2-D membrane protein crystals: dynamics, crystal order, and fidelity of structure analysis by electron microscopy. Membrane protein reconstitution into two-dimensional (2-D) ordered arrays is described. The assembly of 2-D crystals may be modeled as a two-step process: the membrane protein is first integrated in the lipid bilayer and then crystallized by removal of excess detergent or lipid and/or by precipitating agents. Lipid-detergent, protein-detergent, and lipid-protein interactions are critical during the first step, while lipid-protein and protein-protein interactions dominate events in the second step. The evidence supporting this model results from quasielastic light scattering analyses and electron microscopy of different lipid-detergent systems and reconstitution experiments with Escherichia coli porin OmpF, Phormidium laminosum photosystem I reaction centers, and integral membrane proteins of mammalian lens fiber cells.


Influence of endothelium in the in vitro vasorelaxant effect of magnesium on aortic basal tension in DOCA-salt hypertensive rat. The objective of this study was to examine the influence of the endothelium on the extracellular magnesium induced relaxation of basal tension in isolated aortas from both mineralocorticoid-salt (DOCA-salt) hypertensive and control normotensive Sprague Dawley male rats. After incubation in magnesium-free physiological salt solution (PSS) (O mM magnesium), the increase of extracellular magnesium (1.2; 4.8 mM magnesium) caused a decrease in aortic tone which was significantly greater when endothelium was disrupted. Magnesium-induced relaxation was also more pronounced when endothelial NO production was blocked by 10(-4) M N omega-nitro-L arginine methyl ester (L-NAME). It is suggested that the vasorelaxation induced by extracellular magnesium is linked to the level of aortic basal tension developed in magnesium-free PSS. The endothelium does not seem to be directly implicated in magnesium-induced vasorelaxation in aortas from normotensive rats. However, in DOCA-salt hypertensive rats, the magnesium-induced relaxation of basal tension was less in the intact aorta (though not when the endothelium was disrupted) when the cyclo-oxygenase pathway was blocked by 10(-6) M indomethacin. These data therefore suggest that extracellular magnesium can promote relaxation by endothelium-dependent and cyclo-oxygenase-dependent mechanisms such as the production of relaxing prostacyclin in isolated aorta from DOCA-salt hypertensive rats.


Actin crosslinking protein EF-1a of Dictyostelium discoideum has a unique bonding rule that allows square-packed bundles. The elongation factor 1a (EF-1a) of Dictyostelium discoideum is an actin crosslinking protein that gives rise to a unique kind of actin bundle. Purified actin and EF-1a were allowed to form bundles and then were characterized by electron microscopy, computed diffraction analysis, and modeling. In these bundles crosslinked actin filaments are rotated by 90 degrees relative to each other, whereas other known crosslinking proteins require filaments to be unrotated. Bundles of actin EF-1a would tend to exclude other actin bundling proteins. EF-1a can thus regulate the state of the actin cytoskeleton as well as regulate protein synthesis.


Spectral analysis of electroencephalography data in athletes with low erythrocyte magnesium. In a population of high level athletes (kayakists) we compared quantitative electroencephalography data in those with low erythrocyte (magnesium magnesium deficit) and those with normal magnesium (controls). Logistic regression showed that the relative power of the alpha frequency band in the occipital lead is the most discriminant (P < 0.05). There was a significant positive correlation between low erythrocyte magnesium and alpha relative power (P < 0.05). An alteration of magnesium homeostasis could explain the occurrence of magnesium deficiency in athletes.


New data on the antiarrhythmic value of parenteral magnesium treatment: magnesium and ventricular arrhythmias. Antiarrhythmic magnesium (Mg) therapy was evaluated in 20 normomagnesaemic patients affected by ischaemic dilated cardiomyopathy (ID) and severe ventricular arrhythmias, and in 10 patients with torsade de pointes (TdP) occurring in the setting of acquired QT interval prolongation. In the group with IDC, magnesium sulphate was given as slow infusions (50 mg/min over 60 min) twice a day for 7 d. This was antiarrhythmic in all of the patients: ventricular premature contractions and couplets decreased from 13,979 +/- 8964 (mean +/- SD) to 382 +/- 265 (P < 0.001), and from 516 +/- 274 to 9 +/- 6 (P < 0.001), respectively; runs of ventricular tachycardia (41.9 +/- 14.2) disappeared by the fifth day of treatment. The efficacy of antiarrhythmic treatment was evaluated by 24 h Holter monitoring obtained in baseline conditions and after 3, 5 and 10 d from beginning of therapy. In patients with TdP, Mg infusions were instituted at a slow rate (50 mg/min) and continued for 2 h after disappearance of Tdp, which occurred within 20 to 30 min from the start of the Mg infusions. These were followed by prophylactic infusions at rate of 30 mg/min for 90 min twice a day over the next 3 to 4 d. No side effects were observed, and heart rate and QTc remained unchanged from baseline values. In conclusion, Mg infusions may be an effective antiarrhythmic treatment for short and medium-term control of severe ventricular arrhythmias associated with IDC, and may prove useful in the acute treatment of TdP, especially in situations where conventional therapy might prove deleterious or difficult.


Effects of increased dietary phosphorus on magnesium balance in very low birthweight babies. The effects of three dietary phosphorus concentrations on magnesium balance in very low birth weight (VLBW) infants were measured. The infants consumed one of three special formulas for 20 consecutive days. Magnesium balance was calculated by measuring food intake, urinary magnesium and fecal magnesium. The highest dietary phosphorus concentration resulted in a higher (P < 0.05) fecal loss of magnesium. Net absorption and net retention of magnesium were lower (P < 0.10) in the high phosphorus group. A modest (33 per cent) increase in dietary phosphorus resulted in a decrease in magnesium absorption in VLBW infants.


Influence of the magnesium content of drinking water and of magnesium therapy on the occurrence of preeclampsia. A reverse relationship was found between the magnesium content of drinking water, ie. an adequate supply of highly available dietary magnesium, and the occurrence of preeclampsia. Where various parts of a settlement receive their drinking water from different sources (for example, surface water or well water) there may be an important difference in the level of magnesium supply to different population groups. In the population studied here, the occurrence of preeclampsia varied pari passu with the magnesium content of the drinking water in different parts of the city. The results show that during pregnancy the magnesium content of serum and erythrocytes decreases. This decrease may be prevented by magnesium therapy, which lowers the incidence of preeclampsia.


Magnesium and immune function: recent findings. Recent findings regarding roles for magnesium in immunocompetence confirm and extend previous knowledge of its participation in natural and adaptive immunity. The detrimental effects of severe magnesium deficiency have been confirmed. There is better comprehension of how magnesium relates to mechanisms that control cellular activities and regulate interactions among cells that affect immune functions. Insight has been gained into how magnesium status affects susceptibility to physiological disorders, such as cardiomyopathy and cancer, that are exacerbated by inflammation and by the chemical mediators of anaphylaxis. More information is needed about the impact of less severe magnesium deficiency and of supplemental magnesium on indicators of immune function. Future studies should explore interactive relationships between Mg and such nutrients as vitamin D to elucidate more completely the roles that Mg can play in optimizing immune function.


Experimental and clinical studies on dysregulation of magnesium metabolism and the aetiopathogenesis of multiple sclerosis. The proposed aetiologies of multiple sclerosis (MS) have included immunological mechanisms, genetic factors, virus infection and direct or indirect action of minerals and/or metals. The processes of these aetiologies have implicated magnesium. Magnesium and zinc have been shown to be decreased in central nervous system (CNS) tissues of MS patients, especially tissues such as white matter where pathological changes have been observed. The calcium content of white matter has also been found to be decreased in MS patients. The interactions of minerals and/or metals such as calcium, magnesium, aluminium and zinc have also been evaluated in CNS tissues of experimental animal models. These data suggest that these elements are regulated by pooling of minerals and/or metals in bones. Biological actions of magnesium may affect the maintenance and function of nerve cells as well as the proliferation and synthesis of lymphocytes. A magnesium deficit may induce dysfunction of nerve cells or lymphocytes directly and/or indirectly, and thus magnesium depletion may be implicated in the aetiology of MS. The action of zinc helps to prevent virus infection, and zinc deficiency in CNS tissues of MS patients may also be relevant to its aetiology. Magnesium interacts with other minerals and/or metals such as calcium, zinc and aluminium in biological systems, affecting the immune system and influencing the content of these elements in CNS tissues. Because of these interactions, a magnesium deficit could also be a risk factor in the aetiology of MS.


Brain and CSF magnesium concentrations during magnesium deficit in animals and humans: neurological symptoms. Magnesium is an essential cofactor for many enzymatic reactions, especially those involved in energy metabolism. Deficits of magnesium are prevalent due to inadequate intake or malabsorption and due to the renal loss of magnesium that occurs in certain disease states (alcoholism, diabetes) and with drug therapy (diuretics, aminoglycosides, cisplatin, digoxin, cyclosporin, amphotericin B). Protracted deficits of magnesium in humans and animals result in neurological disturbances, including hyperexcitability, convulsions and various psychiatric symptoms ranging from apathy to psychosis, some of which can be reversed with magnesium supplementation, others requiring correction of the dysregulation mechanism. Although the role of magnesium in neuronal function is not completely understood, a lowering of CSF or brain magnesium can induce epileptiform activity and there is an association between decreased CSF magnesium and the development of seizures. CSF concentrations of magnesium are normally higher than magnesium plasma ultrafiltrate (diffusible) concentrations due to the active transport of magnesium across the blood-brain barrier. Under conditions of magnesium deficiency, CSF concentrations decline, although this decline lags behind and is less pronounced than the changes observed in plasma magnesium concentrations. Decreases in CSF magnesium concentrations correlate with the alterations observed in extracellular brain magnesium concentrations in animals following the dietary deprivation of magnesium. CSF magnesium concentrations can readily be repleted following magnesium supplementation, although high dose magnesium therapy, such as that used in the treatment of convulsions in eclampsia, will only increase CSF magnesium concentrations to a very limited degree (approximately 11-18 per cent) above physiological concentrations. Greater increases in CSF magnesium may occur in neonates since neonatal swine, following treatment with magnesium, have CSF magnesium concentrations that are similar to their plasma concentrations. There has been a recent resurgence of interest in magnesium deficiency and its neurological consequences due to the finding that magnesium, at physiological concentrations, blocks N-methyl-D-aspartate (NMDA) receptors in neurones. NMDA receptors are normally activated by glutamate and/or aspartate which represent the principal neurotransmitters for excitatory synaptic transmission in vertebrate CNS. Magnesium deficiency produces epileptiform activity in the CNS which can be blocked by NMDA receptor antagonists. Other mechanisms, including alterations in Na+/K(+)-ATPase activity, cAMP/cGMP concentrations and calcium currents in pre- and postsynaptic membranes, may also be at least partially responsible for the neuronal effects associated with low brain magnesium. Further studies are necessary to increase our understanding of the neurological implications of magnesium deficit in the central nervous system.


Bone marrow imaging in plasma cell dyscrasias: review of 130 cases. Skeletal radiography, bone and bone marrow scintigraphy have been performed in 130 patients with plasma cell dyscrasias (119 multiple myeloma, 9 MGUS and 2 Waldenström disease). Our results confirm: 1) that radiography is much more sensitive than scintigraphy in the identification of the lesions typical of myeloma, but in the first stage bone scintigraphy and especially bone marrow scintigraphy are more sensitive than x-ray for the detection of regions affected by focal lesions; 2) that bone scintigraphy is of particular value in detecting some abnormalities in specific sites not fully visualized by x-ray; 3) that bone marrow scintigraphy is a valuable diagnostic tool in the early stage of myeloma, especially for evaluating the progression of the disease, because it is able to demonstrate not only focal lesions, but also bone marrow expansion. We believe that bone marrow scintigraphy may be a useful technique in the early diagnosis and follow-up of multiple myeloma, particularly in the detection of unusual forms (i.e., "smouldering" myeloma), but it remains only an "additional" technique for bone imaging.


Evaluation by captopril renal scintigraphy and echo-Doppler flowmetry of hypertensive patients at high risk for renal artery stenosis. Sixty-three hypertensive patients with probability of obstructive renal artery disease underwent both Captopril renal scintigraphy (CRS) and echo-Doppler flowmetry (EDF) before undergoing renal angiography. Angiography revealed renal artery stenosis (RAS) in 42 patients (unilaterally in 26 and bilaterally in 16). The sensitivity and specificity in the identification of RAS > or = 50% were 90% and 94%, respectively for Captopril renography, and 85% and 78% for echo-Doppler flowmetry. Captopril renography correctly identified stenoses greater than 50%, which is usually held to be the limit of hemodynamic significance. While the Doppler examination was more sensitive than Captopril renography (sensitivity 79% versus 64%) in the detection of all degrees of RAS, less information on the functional significance of RAS was provided. Both CRS and EDF could be usefully employed to assess kidney perfusion, but their appropriate clinical use must take into account inherent differences between the two techniques.


Quantitative evaluation of 99mTc-hexamethylpropylenamineoxime brain SPECT in childhood-onset epilepsy. In 10 patients with childhood-onset epilepsy, quantitative evaluation (QE) of interictal regional cerebral blood flow (rCBF) using technetium-99m-hexamethylpropylenamine oxime (99mTc HMPAO) single-photon emission computed tomography (SPECT) was correlated with seizure foci localized by electroencephalography (EEG). Eighty regions of interest (5 x 5 pixels) were placed at five different neocortical areas in both cerebral hemispheres, in coronal and transaxial planes. Mean counts/pixel were calculated for each region and multiple right-left comparisons were done. Quantitative evaluation of 99mTc-HMPAO increased detection of rCBF abnormalities by 26%. Abnormal EEG patterns correlated with abnormal rCBF in 75% of cases (Phi = 0.788, p < 0.001), and with visually detected abnormalities in 50% (Phi = 0.493, p < 0.001). Discordance between EEG and SPECT was most frequent in patients with non-localizing EEG (n = 3). In childhood-onset epilepsy, quantitative evaluation of brain perfusion scans provides: (a) objective estimates of interictal rCBF; (b) more precise detection of epileptogenic foci, when used to complement EEG.


67Ga-citrate imaging in rhabdomyosarcoma. A 22-year-old female patient with a swelling in the right forearm near the elbow underwent a 67Ga-citrate scan because of paraesthesia on the ulnar side of the right hand. The 67Ga total body scan showed intense focal uptake on the forearm in the same position as the swelling. At surgery a histological diagnosis of alveolar rhabdomyosarcoma was made. Five months later, a repeat 67Ga scan was normal. Eight months after the diagnosis, the patient complained of pain in the left lumbar region extending to the hypogastric area. A third 67Ga scan showed intense uptake near the spinal column which at surgery was found to be a metastasis of the primary tumor.


[The transcatheter recanalization of occluded portosystemic shunts]. The authors present their personal experience in percutaneous treatment of portosystemic shunt occlusion and stenosis by percutaneous transluminal angioplasty (PTA) and fibrinolytic local infusion. Twelve patients with portosystemic shunt stenosis or occlusion were percutaneously treated. In 8 patients only PTA was performed, 4 were treated with local fibrinolytic infusion, in 3 of the latter cases this treatment was followed by PTA. In all 12 patients recanalization was successful and non complications arose. Six patients died in the following 15 months, none due to rebleeding. In 5 of these patients the shunt was patent at post-mortem examination. In the 6 patients still alive in the follow-up period (2 to 25 months, mean 14.5 months) the shunt was patent in 4 and occluded in 2. percutaneous treatment with PTA or fibrinolytic local infusion is preferable in non-functioning portosystemic shunt; further surgery is always extremely risky in such patients.


[The clinical importance of physiopathological studies of the bile salts performed using the gamma-emitting bile acid SeHCAT]. The availability of the gamma-labelled bile acid 75SeHCAT, that allows a non-invasive assessment of the enterohepatic circulation of bile acids, has prompted in the last 10 years the implementation of several studies involving wide series of normal subjects and patients with various organic and functional bowel disorders. The clinical indications for performing a SeHCAT test have been clearly defined: the test can identify with high accuracy, in the setting of the irritable bowel syndrome, the patients with bile acid malabsorption that can be confidently and successfully treated with cholestyramine; it can also assess whether, and to what extent, the diarrhoea presenting in patients with intestinal organic disorders is due to bile acid malabsorption, permitting an optimal therapeutic strategy to be designed. The parameters of the hepatic handling of SeHCAT after bolus intravenous administration have been characterized in normals, and studies on various chronic hepatic disorders are now in progress. Interesting results are emerging from studies performed in patients with chronic non-obstructive cholestatic disease, where a specific defect in the excretion rate of SeHCAT is present: these studies may cast more light on the abnormalities of bile secretion and on the mechanism of action of drugs used to treat this condition, forming the rationale for the use of intravenous SeHCAT for hepatobiliary dynamic scintigraphy as a sophisticated liver function test. In conclusion, the SeHCAT test has become an important diagnostic tool for the gastroenterologist studying the diarrhoea, and awaits more studies to be used also by the hepatologist. The relatively long physical half-life of 75Se (180 days), preventing a wider use of the test, could theoretically be overcome by the synthesis of a similar gamma-labelled bile acid with a shorter half-life.


Diabetes in aborigines and other Australian populations. The aetiology of diabetes mellitus is reviewed in the light of Australian epidemiological studies. The prevalence of diabetes has been studied in a wide variety of Australian settings. Comparisons of prevalences in Aborigines and other populations suggest that occurrence of this disease has both genetic and environmental determinants. Diet and obesity are associated with diabetes, but to increase physical exercise may be the most feasible intervention. Public health approaches are discussed.


[Ileal adenocarcinoma in Crohn's disease. A report of 2 cases]. The incidence of intestinal adenocarcinoma in Crohn's ileal disease is reported in the literature to be higher than in the normal population. The authors report two cases of adenocarcinoma observed during the course of Crohn's ileitis and, by comparing these findings with earlier published data, highlight their characteristics. Two patients, a 53-year-old woman and a 62-year-old man, are reported as suffering from Crohn's ileitis. The woman underwent resection of the right colon with ileo-transversostomy due to stenosis twenty years earlier, whereas diagnosis in the male patient dates back to an appendicectomy 11 years earlier. Surgery, which was performed in both due to subocclusion which failed to respond to steroid therapy, showed the typical alterations of Crohn's disease. An adenocarcinoma was also found in both patients in the stenotic zone with highly dysplasic foci. The man presented a monoclonal gammopathy of an IgA-type with light lambda chains and Bence-Jones' proteinuria. Both patients are living and enjoy apparently good health respectively 2 and 6 years after surgery. The authors emphasize that the association between Crohn's ileal disease and intestinal adenocarcinoma cannot be considered casual. In the literature the relative risk is reported to be between 6 and 320 times higher, with approximately 1 out of 350 patients suffering from both diseases contemporaneously. In the series reported earlier, 2 cases of carcinoma were diagnosed in 38 Crohn's patients studied over a period of 12 years out of a total population of 114000 inhabitants, with a frequency of carcinoma of 5.13% compared to 0.3% reported in the literature. The incidence of Crohn's disease was 2.84/100000 per year.(ABSTRACT TRUNCATED AT 250 WORDS)


Future directions for mental health services in Australia. The last decade has seen a marked increase in the attention given to mental health policy and services at both a state and national level. Mental health consumers, carers, service providers, and a number of professional bodies have contributed to the scrutiny of what had been a relatively neglected area. The release of Australia's first National Mental Health Policy is a milestone in the development of a national focus on mental health promotion, prevention and the provision of enhanced services for persons with mental disorder and mental health problems. This paper discusses briefly the directions promoted in the national policy, including mental health promotion, reorientation of mental health services, the nongovernment sector, consumer rights, intersectoral links, service quality, research and evaluation.


Availability of cigarettes to minors.

Availability of cigarettes to minors. Legislation banning the sale of cigarettes to minors is potentially a cost-effective means of reducing smoking rates among adolescents. Such legislation has been in existence in Australia for over 80 years. Two studies examined the retail industry's adherence to the sales ban in two regions of New South Wales in 1990. The first study was a survey of 1,849 12- to 15-year-old adolescents from 12 high schools in New South Wales, providing data on self-reported purchasing of cigarettes from retail outlets by minors. In all, 38 per cent reported having purchased cigarettes illegally. A second study was undertaken to determine the proportion of retail shops which sell cigarettes to apparently underage youth. Two 16-year-olds who looked young for their age attempted to purchase cigarettes from 101 different retail outlets in one region of New South Wales. No challenge about age was made for 70 per cent of purchases, and proof of age was requested on only 15 per cent of occasions. The results suggest that legislation banning sales of cigarettes to minors requires strong enforcement procedures to be effective.


Patterns of service utilisation following the 1989 Newcastle earthquake: findings from phase 1 of the Quake Impact Study. A screening questionnaire was distributed to 5,000 adult members of the community six months after the 1989 Newcastle earthquake, with a response rate of 63 per cent (n = 3,007). The mean age of respondents was 46.7 years and 58 per cent were female. Subjects' earthquake experiences were rated in terms of weighted indices of exposure to threat and disruption. Psychological morbidity was measured using the General Health Questionnaire and the Impact of Event Scale. Subjects were asked to indicate which of a range of general and disaster-related support services they had used in dealing with the stressful effects of the earthquake. It was estimated that 21.3 per cent of the adult population used general and/or disaster-related support services. Users of these services reported greater exposure to threat and/or disruption and had higher levels of psychological distress than nonusers. However, a high level of use of general services and reliance on medical services were related more to psychological morbidity than degree of exposure to earthquake-related events. Overall, the Newcastle community's needs for assistance in the aftermath of the earthquake were effectively absorbed by the existing support services and the resources marshalled to supplement those services. Individuals and organisations mobilised following natural disasters need to be strengthened by enhancing the capacity of support service workers to identify and manage psychological distress in their clients.


Public knowledge about characteristics of moles and melanomas. In a study aiming to determine public knowledge about moles and melanomas 590 residents of Victoria aged 14 and over were interviewed in a face-to-face household survey. The majority believed that moles were primarily raised lesions. Recognition of the term melanoma was high (91 per cent), but many held misconceptions about key characteristics. Many thought an early melanoma was raised (20 per cent) or could be raised (42 per cent), compared with only 10 per cent who thought it was flat. Fifty per cent of respondents thought being ugly was a common characteristic. In response to photographs of skin lesions, a late melanoma, seborrhoeic keratosis and a squamous cell carcinoma were most likely to be identified as needing to be seen by a doctor, while a normal raised mole and two early melanomas were least likely. The data suggest that a large proportion of the community have misconceptions about the early signs of melanoma. Education programs are needed to inform the public that most early melanomas are flat. Strategies which might confuse this message, such as likening melanoma to moles, should be avoided.


A survey of infertility, surgical sterility and associated reproductive disability in Perth, Western Australia. Infertility, surgical sterility and associated reproductive disability were studied in a stratified cluster sample of 1,511 couples with women aged 16 to 44 years resident in metropolitan Perth in 1988. Sixteen couples were omitted from analysis because of missing data. The proportion of couples affected by current infertility was 3.5 per cent (53 of 1,495), and 67.9 per cent of these (36 of 53) had a reproductive disability, meaning that they were unable to achieve their desired level of reproductive function. Those affected by surgical sterility accounted for 37.1 per cent (555 of 1,495), and of these couples 2.0 per cent (11 of 555) had a reproductive disability. Empirically, the prevalence of both infertility and reproductive disability peaked at ages 30 to 34 years in the female partner. Of the factors studied, infertility was associated with surgery for a ruptured appendix, a history of pelvic inflammatory disease and number of sexual partners. In 10 of the 47 couples with reproductive disability, contraceptive sterilisation had been a cause of later regret. Most other cases were due to infertility. Almost one half of couples with reproductive disability had sought treatment. The affected couples had at least one child from the current union in 23 of the 47 cases of reproductive disability. The results support the need for development of a strategy to prevent infertility and other causes of reproductive disability.


A survey of contraceptive use and unplanned pregnancy in Perth, Western Australia. Contraceptive use and unplanned pregnancy were studied in a stratified cluster sample of 1,511 couples with women aged 16 to 44 years resident in metropolitan Perth in 1988. Twenty-one couples were excluded from analysis owing to missing data. The proportion of couples using contraception was 76.8 per cent (1,144 of 1,490), and all but three of the remaining couples gave a reason for nonuse. Among users, surgical sterilisation made up 42.3 per cent (484 of 1,144) of all methods, with a slight predominance of tubal ligation over vasectomy. Oral contraceptives accounted for just over half of nonsurgical methods. Comparisons with a Victorian survey performed in 1978 suggested that surgical methods and condom use may have increased, whereas use of oral contraceptives and intrauterine devices may have fallen. Unplanned pregnancies conceived during the 12 months before the interview affected 3.4 per cent (51 of 1,490) of respondents. The incidence of unplanned pregnancy was four times higher in couples with inconsistent usage patterns of contraception.


Evaluating the petrol-sniffing prevention programs of the Healthy Aboriginal Life Team (HALT). The evaluation of the Healthy Aboriginal Life Team's (HALT) petrol-sniffing prevention programs at Yuendumu, Kintore and the Pitjantjatjara Lands first required a specification of program outcome--which was not changed in the enumerated prevalence of petrol sniffing, but alteration in parental perceptions of the relevance and effectiveness of families' nurturant authority over recalcitrant youngsters. The evaluation then proceeded by a series of interviews with resident or ex-resident adults (Aboriginal and non-Aboriginal) of Yuendumu, Kintore, Kiwirrkurra, Ernabella, Indulkana and Fregon. Adults articulated their efficacy in different ways in each place. Some favoured the conclusion that HALT had helped them, others clearly identified HALT as an obstacle to or a distraction from the implementation of other preventive and curative community-based action. We discerned a ferment of cultural adjustment in the distribution of authority over children among parents and welfare agencies. We caution against finding in HALT's successes a model procedure for benign interventions into such cultural adjustment.


Smoking in aborigines and persons of European descent in southeastern Australia: prevalence and associations with food habits, body fat distribution and other cardiovascular risk factors. As part of a population-base study of risk factors for heart disease, we aimed to establish the prevalence of smoking and to identify associations between smoking and other risk factors in Australian Aborigines (n = 306) and persons of European descent (n = 553) in two country towns. Smoking prevalence was first analysed as a dichotomy (current smokers compared with nonsmokers), and according to three levels of exposure (< 10, 10-20 and > 20 cigarettes per day), and two levels of nonexposure (never and former smoker). Other behavioural, biochemical and physical variables were included in multivariable analyses. Of the Aborigines, 64.4 per cent (95 per cent confidence interval (CI) 59.0 per cent to 69.8 per cent) were current cigarette smokers, compared with 22.8 per cent of non-Aborigines (CI 19.3 per cent to 26.3 per cent). For persons aged 13 to 54 years, using the five categories of exposure, smoking in Aborigines again far exceeded that in non-Aborigines in all age groups (for males chi 2 = 72.8, for females chi 2 = 94.6, 4 df, P = < 0.0001 for both sexes). In non-Aboriginal females, the highest prevalence was in the youngest group (56 per cent of those aged 13 to 17 years). Food habit was associated with smoking. Subjects who ate meat without trimming the fat were more likely to smoke. In Australian country towns, Aborigines and all young women need smoking cessation programs. The nutritional status of smokers requires further study.


Assessing community attitudes toward medical practitioner authority. Despite the widespread belief that medical authority is under increasing challenge, no adequate research instrument has been available to measure relevant community attitudes. This paper reports the development of the Attitude Toward Medical Practitioners Scale (the AMPS). Samples of Australians (in total N > 1000) completed the AMPS, using three different procedures. The reliability of the scale, assessed by coefficient alpha, ranged from 0.80 to 0.86. A principal component analysis of the AMPS yielded loadings on each item exceeding 0.3 on the first unrotated factor; subsequent varimax rotation revealed dimensions associated with critical attitudes to doctors and evaluations of doctors' interpersonal competence and technical expertise. Positive and significant correlations between the AMPS and one measure of the General Attitude toward Institutional Authority (GAIAS) strongly suggested that the scale is consistent with generalised evaluations of community authorities. The specific validity of the AMPS was supported for each of three samples, using as validating criteria respondent ratins of the last doctor visited, satisfaction with the consultation and reported compliance with the doctor's advice. Significant improvements were found in the prediction of each of these criteria by the addition of the AMPS to contributions made by the GAIAS and the demographic variables, age and sex. The AMPS is an appropriate measure for assessing community attitudes towards medical practitioners conceived as institutional authorities, at least in the Australian context.


Occupational injury and disease among patients presenting to general practitioners in a community health centre. A prospective survey was conducted of all patients presenting over a six-month period to the primary medical care unit of a community health centre in an urban industrial area to determine the number and types of work-related injuries and disease, the causes, and details of the injured workers and their workplaces. Two-hundred and eighty-three patients, 7.2 per cent of the total number of patients attending, were diagnosed as having a work-related injury or disease; 250 patients had occupational injuries and 33 had occupational diseases. The most common injuries were open wounds, sprains and strains, contusions and eye injuries; the most frequent diseases were musculoskeletal strain syndromes, dermatitis and respiratory conditions. Most of those injured were skilled tradesmen or labourers from small (less than 30 employees) or medium-sized (30 to 99 employees) manufacturing workplaces. In five of the local medium-sized workplaces, more than 10 per cent of the workforce presented with occupational injury or disease in the six months. The mechanisms of injury for common injuries such as back strain and eye injuries are described. Most patients were managed totally within the primary care setting. Thirty per cent of all patients surveyed received a worker's compensation certificate. It is possible that occupational diseases were underdiagnosed and that worker's compensation was underutilized. The information obtained from the survey is being used in planning prevention.


General practitioner services under Medicare. This paper examines how general practitioner numbers, bulk-billing rates and sociodemographic variables determined usage of general practitioners and services delivered over the period from 1984 to 1990. A 10 per cent sample of patient services, maintained by the Commonwealth Department of Health, Housing and Community Services, provided the data. Data were aggregated into 148 electorates. Separate regression analyses examined the determinants of the proportion of the population attending a general practitioner and of the number of general practitioner services delivered per patient. Determinants of the growth of these levels over the seven-year period were also examined. Region (metropolitan versus rural), age structure and general practitioner supply were significant factors in these analyses. Bulk-billing rates explained nine per cent of variance in patient numbers and 22 per cent of variance in service numbers after sociodemographic variables and general practitioner supply had been taken into account. The analyses suggest that bulk-billing and general practitioner supply influence the behaviour of patients and doctors and that the effect of bulk-billing is independent of indices of medical need. This implies that bulk-billing may increase service rates and this increase is not clearly directed to improving access to medically necessary services. Because no measures of treatment outcome are available. it is not possible to decide whether the effects observed represent an improvement in health care or are better seen as overuse by patients and demand inducement by practitioners.


Accuracy of asthma death statistics in Australia. Asthma mortality statistics issued by the Australian Bureau of Statistics (ABS) were compared with clinical data from a survey of asthma mortality. Deaths in Victoria from May 1986 to April 1987 containing 'asthma' in Parts 1 or 2 of the death certificate (N = 405) were reviewed. For each subject, the cause of death attributed by the Victorian Asthma Mortality Survey was compared with the ABS cause of death, by age and sex of the subject. Information on 393 of the 405 deaths investigated by the Victorian Asthma Mortality Survey was analysed. The ABS estimate of the total number of asthma deaths in Victoria was 47 per cent higher than the estimate of the Victorian Asthma Mortality Survey. In subjects under 50 years of age the two estimates were within 10 per cent. The difference between the estimates increased with age at death for persons over 50 years old and was equivalent for males and females. If the assessment by the Victorian Asthma Mortality Survey of the number of deaths due to asthma is accepted as accurate, then the ABS estimate of asthma deaths was reliable for those under 50 years of age. In those who died at an older age, the ABS significantly overestimated the number of deaths due to asthma in Victoria.


Death certification in Western Australia--classification of major errors in certificate completion. We aimed to develop a method to classify those errors in the completion of death certificates arising from misunderstanding of the certification process. We reviewed 430 Western Australian death certificates registered in March 1990 using a method devised to differentiate between major and minor errors. Major errors were found in 16 per cent of certificates (95 per cent confidence interval 12 to 20 per cent). The error rate did not vary significantly between city and country areas, nor between teaching hospitals and other locations. The method was validated on a separate sample of 120 certificates. It has potential as a tool to monitor a critical but neglected step in the production of mortality statistics and to assess understanding of the process of death certification.


The rationing of health care: should Oregon be transported to Australia? The Oregon Plan is an ambitious attempt to address the widespread problem in the United States of a growing number of individuals who are without private health insurance and are not eligible for federal assistance programs. Its aim is to provide universal access for all Oregonians, without increasing total health care expenditure, by restricting the cover of some treatments. It has aroused interest in Australia and elsewhere. The appeal of the Oregon Plan lies in its explicit approach to rationing, in community participation in setting priorities, and the use of a cost-effectiveness framework. This paper describes the beginnings and the development of the Oregon Plan, and compares the actual development of the Plan with the rhetoric. There is a gap between the rhetoric of the Plan and its reality. The Oregon plan should be considered in the context of the United States health care system. We compare the American problems with those facing the Australian health care system and conclude that the answer to the question of whether Oregon should be transported to Australia is no. Nevertheless there are elements of the rhetoric of the Plan which could be applied in rationing health care in Australia.


QSAR, diagnostic statistics, and molecular modelling of antiallergic acrylamide derivatives. Quantitative structure-activity relationships of antiallergic N-[4-[4-(diphenylmethyl)-1-piperazinyl]-butyl]-3-(3-pyridyl)acr yl-amide s were studied. It was shown that the biological action depends on lipophilic and steric substituent features; apolar but small groups improve activity. Diagnostic statistics indicated that the QSAR equation is relatively robust. It was hypothesized from molecular modelling that the substituents influence primarily the pharmacokinetic-toxokinetic behavior of the compounds.


QSAR study of HMGR inhibitors: 7-(heteroaryl)-3,5-dihydroxy-6-heptenoic (-heptanoic) acids. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) inhibitory activity of pyridine- and pyrimidine-substituted 3,5-dihydroxyhept-6(E)-enoic acids and 7-(1H-pyrrol-3-yl)-substituted-3,5-dihydroxyhept-6(E)-enoic (-heptanoic) acids was quantitatively analysed using hydrophobicity, molar refractivity, electronic and Verloop's steric parameters. The results obtained were comparable to the earlier findings of 7-(aryl/biphenyl)-3,5-dihydroxy-6-heptenoic (-heptanoic) acids. The R'4-substituent of the aryl substituent of heteroaryl moiety was found to influence the inhibitory activity through its steric and electronic properties, and the equations confirm that substituents with minimum steric bulk, positive polar and negative resonance constants lead to better inhibitory activity. The changes in the heteroaryl moiety of the inhibitors did not correlate with the activity. Probably, the heteroaryl moiety of the inhibitors may be serving as a skeletal framework to hold the surrounding hydrophobic substituents.


Structure-activity relationships of N-n-propyl-2-(4-fluoro-3-hydroxyphenyl)ethylamine derivatives as dopamine receptor ligands. A series of N-n-propyl-2-(4-fluoro-3-hydroxyphenyl)ethylamine derivatives obtained by introducing on nitrogen atom a 2-phenylethyl moiety (with aromatic nucleus substituted at 3 or 4 position with fluorine, chlorine or hydroxy and methyl groups), as well as a 2-cyclohexylethyl or 3-phenylpropyl groups were synthesized. These substituents can interact with the D2 accessory binding site pi 3. The affinities of new compounds for D1 and D2 subtypes of dopamine (DA) receptor were measured in a test involving displacement of [3H]SCH 23390 and [3H]spiperone, respectively, from homogenates of rat striatum. The new derivatives are selective for D2 sites, and are more potent than the parent compound N-n-propyl-N-(2-phenylethyl)-2-(4-fluoro-3-hydroxyphenyl)ethylamine 2a. The N-n-propyl-N-[2-(4-hydroxyphenyl)ethyl]-2-(4-fluoro-3-hydroxyphenyl) ethylamine (11f) is the most potent and selective member in the series. Other derivatives are less effective but are as potent as the D2 agonist RU 24213. The results indicate that the pi 3 site is a rather large lipophilic pocket which can accommodate not only aromatic nuclei, but also the cyclohexyl group.


Tumor necrosis factor alpha production as a possible predictor of relapse in patients with multiple sclerosis. No biological parameter is currently available as a specific marker of multiple sclerosis (MS) activity. The aim of this study was to determine whether an evolution of the neurological disability is associated with a modified profile of cytokine production. Clinical disease activity was quantitated by the Kurtzke's expanded disability status scale (EDSS). Whole blood was stimulated with phytohemagglutinin (PHA) for 2 hours at 37 degrees C and the activated plasma was assayed for Tumor necrosis factor alpha (TNF-alpha) and Interleukin-1 beta (IL-1 beta). Relapsing-remitting MS patients enduring a relapse (RRMS, in relapse) (721 +/- 58 pg/ml, n = 27) and chronic progressive MS (CPMS) patients (516 +/- 33 pg/ml, n = 17) had an higher TNF-alpha production capacity as compared to healthy subjects (143 +/- 25 pg/ml, n = 17), RRMS, stable patients, (123 +/- 11 pg/ml, n = 26) or other neurological diseases (OND) without immunological or inflammatory disease in the peripheral immune compartment (131 +/- 24 pg/ml, n = 14) (t test: p < 0.0001). IL-1 beta production was also significantly higher but to a lesser extent in the same conditions. Concentration of TNF-alpha was also found to be significantly higher in the cerebrospinal fluid (CSF) of CPMS patients (199 +/- 7.8 pg/ml, n = 7, p < 0.0001) but also in RRMS, in relapse (149 +/- 5.7 pg/ml, n = 11, p < 0.05) as compared to RRMS, stable (130 +/- 4.4 pg/ml, n = 7) or OND without inflammatory or immunological disease of the central nervous system (CNS) (142 +/- 6.2 pg/ml, n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)


The biosynthesis of tumor necrosis factor during pregnancy: studies with a CAT reporter transgene and TNF inhibitors. Tumor necrosis factor (TNF) is a protein hormone which mediates diverse inflammatory conditions, but which also may be involved in physiologic processes. To detect the expression of TNF as it might occur in normal tissues we developed a transgenic mouse line bearing a reporter gene construct in which the INF coding sequence and introns are replaced by a chloramphenicol acetyl transferase (CAT) coding sequence. In these animals, expression of CAT within tissues has been shown to reflect TNF production. We now report upon the pattern of CAT expression that is observed during normal pregnancy. CAT is constitutively expressed in both the fetal and maternal thymuses, and in the placenta, but in no other tissues. Placental CAT activity first becomes measurable at day 13 of gestation, peaks at day 16, and is maintained at high levels until parturition. Crosses between transgenic and non-transgenic mice clearly indicate that the trophoblast, rather than the decidua or uterus, is the source of CAT activity. A soluble TNF receptor/IgG heavy chain chimeric protein, which strongly inhibits TNF activity in vitro and in vivo, was shown to cross the placenta, gaining access to the fetal circulation when administered on the maternal side. However, the chimeric protein did not interrupt pregnancy, and had no obvious effect on fetal development, suggesting that TNF may not be required for completion of a normal gestation.


Expression of CD23 by human bone marrow stromal cells. CD23 is a surface antigen expressed by a variety of human hematopoietic cells and shown to display multiple biological functions. In present work, we assayed CD23 expression by human bone marrow (BM) or by stromal cells derived from this tissue. While freshly isolated BM-cells showed low CD23 expression, a subset of long term BM-culture (LTBMC)-derived stromal cells expressed CD23 mRNA at high levels in their steady state and secreted soluble CD23 in their culture supernatants. To assay the role of CD23 in LTBMC, these cultures were initiated in the presence of neutralizing anti-CD23 mAb. A dramatic decrease in total numbers of hematopoietic cells and CFU-GM recovery was observed in these cultures as compared to controls. These data suggest a role of CD23 expression in stroma cell functions and further confirm the ability of this antigen to regulate human hematopoietic cell development.


Simultaneous quantitation of cytokine mRNAs in interleukin-1 beta stimulated U373 human astrocytoma cells by a polymerisation chain reaction method involving co-amplification with an internal multi-specific control. The measurement of cytokine mRNA levels is of fundamental importance in the understanding of diverse pathological states. We present a simplification of a polymerase chain reaction-based technique which permits the simultaneous measurement of up to 20 cytokine mRNAs, together with those of several other cellular products, including beta 2-microglobulin and beta-actin. The technique makes use of internal standards bearing multiple PCR primer sites which are identical to those on the mRNAs to be assayed. Known quantities of the standards are added to the cellular RNA and the mixture is co-reverse transcribed and co-amplified. The simplifications described here are based on the fact that each pair of amplicons accumulates in a constant ratio even in the plateau phase of amplification. As a result, no preliminary experiments to determine the limits of the exponential phase of amplification are necessary; the same number of cycles may be chosen for all the mRNAs to be measured, whatever their level in the mixture might be; pipetting errors are avoided since all calculations are based upon the relative quantities of co-amplified material. Here we illustrate the method through a quantitative study of the expression of cytokine mRNAs in U373 human astrocytoma cells before and after stimulation with IL-1 beta. Quantitation was carried out either by incorporating radioactivity in the amplicons or by fluorescence measurements after propidium iodide staining. Only very low numbers of transcripts for IL-6, IL-8, CSF-1, MCP-1 and either Gro alpha or Gro beta were detectable in unstimulated cells. The levels of these cytokine mRNAs increased dramatically following IL-1 beta stimulation and, in addition, transcription of IL-1 beta, TNF alpha, GM-CSF, G-CSF, Gro gamma and MCP-1, some of which have not previously been detected in U373, was initiated in the stimulated cells. At the same time we found that transcripts for IL-2, IL-3, IL-4, IL-5, IFN gamma, huMlP1 alpha and huMlP1 beta were totally absent in this cell line. These results suggest a potentially important role for astrocytes in the local amplification of inflammatory responses in the brain.


Subcellular distribution in vivo of testosterone and salt extractability of nuclear androgen complexes in the prostate and prostatic adenocarcinoma: effect of estrogen treatment. The distribution of injected [3H]testosterone into nuclear (Nt) mitochondrial-microsomal (Mp) and cytosolic fractions (Cs) obtained from hormone-dependent R-3327 Dunning tumor, dorsal prostate, ventral prostate and heart ventricle, as a non-target tissue, was studied. Since it has been suggested that salt resistant steroid receptor complexes may represent acceptor sites, extractability of nuclear androgen complexes with high KCl (0.6 M) solution was also determined. Both orchiectomized (Or) and estrogen treated (E2) rats were used. The distribution of bound radioactivity between Nt and Cs fractions was very similar in tumors, dorsal and ventral prostate, being approximately 50% and 10% in Nt and Cs, respectively. In heart the corresponding figures were 15% and 12%, respectively. The concentration of radioactivity/mg protein in nuclear KCl-extract (Ne) from tumors was approximately 10-fold higher than that in the salt-resistant (Nr) fraction and also nearly 10-fold higher than that in Cs. Similar distribution patterns were observed in dorsal and in ventral prostate, but the concentration in Ne from ventral prostate was higher than that from tumors or dorsal prostate. Both total and bound radioactivity in Cs from heart was similar to that in the tumors, whereas the concentration in Ne from heart was < 2% of that in Ne from tumors. No significant differences were found in the distribution of radioactivity in tumors or tissues obtained from Or or E2 rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Leiomyoma-derived growth factors for smooth muscle cells. The presence of growth substance(s) for smooth muscle cells and fibroblasts was documented in extracts of human leiomyoma tissues (Koutsilieris et al, Am. J. Obst. Gynecol. 163: 1665-1670, 1990). In this study leiomyoma tissues (700 grs) obtained at surgery were extracted and purified using CM-sepharose, heparin-sepharose and reverse-phase high performance liquid chromatography (r-HPLC). The mouse NIH/3T3 cell fibroblasts (ATCC-CRL 1658) and the rat smooth muscle cells A10 (ATCC-CRL 1476) were used as indicator bioassay systems assessing the proliferative effect (tritiated-thymidine incorporation and cell number) of leiomyoma extracts. The profile of peptides purified by cm-sepharose, heparin-sepharose and by r-HPLC was analyzed by standard SDS gel electrophoresis. An overall 50,000 fold purification was achieved of a preferentially acting material on rat aorta smooth muscle cells (A10 cells). This material possessed mitogenic activity equivalent to epidermal growth factor (EGF) on A10 smooth muscle cells, in vitro. We believe that the final chemical definition of such leiomyoma-derived growth substance with preferential action on smooth muscle cells may elucidate the paracrine and/or autocrine interactions among myometrial cells and thus could provide new clues for the pathogenesis of uterine leiomyomas.


Induction of anti-Escherichia coli activity in mice by phenothiazines, benzo[a]phenothiazines and benz[c]acridines. The abilities of 14 phenothiazines, 8 benzo[a]phenothiazines and 12 benz[c]acridines to induce anti-Escherichia coli activity in mice were compared. Pretreatment with several benzo[a]phenothiazines or benz[c]acridines protected mice from lethal infection of Escherichia coli in a dose-dependent manner, whereas most of the phenothiazines induced much weaker anti-Escherichia coli activity. However, direct contact of Escherichia coli with these compounds or their administration just after bacterial inoculation were ineffective. These data suggest the immunopotentiation activity of benzo[a]phenothiazines and benz[c]acridines.


Stimulation of host resistance against tumors by glycyrrhizin, an active component of licorice roots. The effect of glycyrrhizin (GR), a Chinese herbal drug extracted from licorice roots, on the host resistance to tumors was investigated in a murine system. Administration of GR to BALB/c mice, which were inoculated s.c. with 1 x 10(6) cells/mouse of Meth A tumors, resulted in either no antitumor effect (8/20, 40%), a delay in tumor growth (9/20, 45%), or elimination of tumor growth (3/20, 15%) in these mice. In addition, the incidence of Meth A solid tumors was inhibited by GR when mice were inoculated with 1.5 x 10(4) cells/mouse or less of Meth A tumor cells, but not 7.5 x 10(4) cells/mouse or more. These results indicate that in this murine tumor system GR has a very weak antitumor effect. When GR at a dose of 20 mg/kg was administered to mice immunized with allogeneic lymphocytes 1 to 9 days after the immunization, the generation of suppressor macrophages (S-M phi) was clearly reduced as compared with that of S-M phi generated in immunized controls. In addition, when allospecific CTL (allo-CTL), which were generated in alloimmunized mice treated with GR followed by in vitro stimulation with allogeneic lymphocytes in a mixed lymphocyte reaction, were adoptively transferred to tumor-bearing mice treated with GR, the antitumor activity of allo-CTL derived from immunized mice treated with GR was markedly enhanced as compared with that of allo-CTL from immunized mice. Furthermore, established solid tumors were completely eliminated when interleukin-2 immunotherapy was performed in these mice in combination with GR treatments, but not interleukin-2 or GR alone.(ABSTRACT TRUNCATED AT 250 WORDS)


Detection of IgM antibodies to Chlamydia trachomatis, Chlamydia pneumoniae, and Chlamydia psittaci from Japanese infants and children with pneumonia. Chlamydia trachomatis (C. trachomatis) is now well established as a pathogen of neonatal inclusion conjunctivitis and infantile pneumonia. C. pneumoniae (TWAR) and C. psittaci also cause pneumonia and other respiratory infections. Serum samples from 223 Japanese infants and children with pneumonia were tested for IgM antibodies to C. trachomatis, C. pneumoniae and C. psittaci. IgM antibodies to C. trachomatis were measured by an enzyme immunoassay (EIA) and by a microimmunofluorescence (MIF) test. IgM antibodies to C. pneumoniae and C. psittaci were determined by MIF. Of 223 patients, 48 (21.5%) were positive for IgM antibodies to C. trachomatis, 11 (4.9%) were positive for C. pneumoniae and 5 (2.2%) were positive for C. psittaci. From nasopharyngeal swabs collected from 87 infants with pneumonia (0 to 1 year of age), we attempted to isolate C. trachomatis with tissue culture. C. trachomatis was isolated from 23 (26.4%) of 87 infants with pneumonia, and IgM antibodies to C. trachomatis were detected in 17 (19.5%) of them. Our data suggest a role for chlamydial infection in childhood pneumonia beyond infancy with both C. trachomatis and C. pneumoniae being contributing pathogens.


Differential effects of butyrate derivatives on human breast cancer cells grown as organotypic nodules in vitro and as xenografts in vivo. The antiproliferative and cytodifferentiating effects of a new stable butyric derivative, monobut-3, were compared using human MDA-MB-231 breast cancer cells grown in three dimension as either in vitro tumor nodules or in vivo xenograft tumors. In in vitro tumor nodules, monobut-3 exhibited marked growth inhibitory effects consistent with the results obtained in monolayer cell cultures. Some functional cell differentiation was also detected in treated nodules. In in vivo xenografts, monobut-3 significantly decreased MDA-MB-231 tumor take but did not affect the rate of tumor growth. No difference was noted in the histological characteristics of the xenografts between untreated and treated mice. Moreover, once monobut-3 treatment was discontinued, tumor growth rapidly resumed in tumor-free animals. The decreased efficacy of monobut-3 in in vivo MDA-MB-231 xenografts as compared to in vitro tumor nodules indicates that factors related to host environment may still limit the clinical effectiveness of this compound.


In vivo 31P magnetic resonance spectroscopy and 1H magnetic resonance imaging of human bladder carcinoma on nude mice: effects of tumour growth and treatment with cis-dichloro-diamine platinum. In vivo 31P NMR spectroscopy and 1H NMR imaging were used to examine the bladder T24B carcinoma in nude mice during untreated growth and in response to chemotherapy by Cis-dichloro-diammine-platinum (CDDP) at a dose of 8 mg/kg i.p. Untreated growth was associated with an increase of inorganic phosphate and phosphomonoesters and a decrease of phosphocreatine. Fast growing tumours and early stage of regrowth after treatment presented a higher phosphocreatine/beta NTP ratio. Following CDDP treatment, 31P metabolite ratios and pH were significantly altered compared with age-matched controls, as early as 6 hours after treatment. Although necrotic area was clearly visible in MRI, no treatment effect could be detected on the images of treated tumours.


Morphohistochemical characterization of suramin--induced chronic toxicity in rat kidney. The effects of a chronic administration of suramin were evaluated on renal parenchyma of young rats. Animals were given suramin 18 mg/kg i.p. twice a week for two months, a treatment schedule equivalent to that used in cancer patients. At the end of the treatment, suramin concentrations in plasma and kidney were assayed and a morphohistochemical examination of renal parenchyma was carried out. Marked and widespread alterations were detected in both cortex and medulla and were associated with elevated tissue suramin levels exceeding 5 mg/g of tissue. The present data demonstrate that suramin induces a severe chronic renal damage in the rat, associated with high drug tissue levels.


In vivo cytotoxicity and antineoplastic activity of a transferrin-daunorubicin conjugate. Transferrin, the major iron-binding protein in the plasma of vertebrate species, is an essential growth factor for proliferating malignant cells. The specific receptor binds diferric transferrin and is endocytosed into the cell. We would like to take advantage of this physiologic phenomenon using an active transferrin-daunorubicin conjugate to target cancer cells. We have compared the in vitro and the in vivo activity of free daunorubicin and of daunorubicin transferrin conjugate on cancer cells. The results suggest that our conjugate is less toxic and more active upon malignant cells than the free drug, daunorubicin, while being less toxic for normal cells.


Measurement of platelet volume using a channelyzer: assessment of the effect of agonists and antagonists. Platelets undergo morphological changes prior to aggregating. This phenomenon is known as the platelet shape change (PSC) and is usually accompanied by at increase in median platelet volume (MePV). We evaluated MePV changes in human platelet rich plasma (PRP) using a high resolution pulse-height analyser ("channelyzer"). Increases in MePV were induced by the addition of low concentrations of known aggregating agents. These agonists showed different patterns in terms of potency, duration and reversibility.


Nucleotide sequence of the third cytokine LD78 gene and mapping of all three LD78 gene loci to human chromosome 17. Cytokine LD78 is a member of a newly identified cytokine superfamily. We cloned the third human gene for the LD78, termed LD78 gamma and the sequence analysis showed that it is a 5'-truncated pseudogene. Exons 2 and 3 and the intron between them are highly homologous to those of the LD78 beta gene, hence, the gamma gene was probably derived from the beta gene. Southern blot analysis of human x mouse somatic hybrid cell DNAs and in situ hybridization experiments mapped all the three gene loci on human chromosome 17q21.1-q21.3. Analysis of DNAs from family members supports our previous finding that the beta and gamma genes on each of the paired chromosome 17 vary in copy number and that the LD78 alpha gene is presumably a single copy. In our analyses of cosmid clones, the LD78 beta gene and the second gene for AT744, which is also a member of the superfamily are closely linked in a head-to-head arrangement. The mechanism of generation of the three LD78 genes is discussed.


Secondary structure analysis identifies a putative mouse protein demonstrating similarity to the repeat units found in CDC4, the G protein beta subunits and related proteins. The predicted protein product of an anonymous clone isolated from a cDNA library prepared from 12 day post coitum (p.c) embryonic mouse heart tissue demonstrated the same segmental repeats previously identified in the cell division control protein, CDC4 and the G protein beta 1 subunit. A search of the protein database subsequently identified three other classes of protein containing the repeat. Secondary structure analyses performed on the repeat sequences revealed a high degree of conservation suggesting that the repeat motif performs a specific function in a diverse range of proteins.


Differential changes of prostanoid synthesis by the gastrointestinal tract, mesenteric vasculature and hepatic portal vein of diabetic rats: comparison between pair and ad libitum feeding. The synthesis of the prostaglandins (PG) I2 (measured as 6-oxo-PGF1 alpha), E2, E2 alpha) and thromboxane (TX) A2 (measured as TXB2) by the mucosal and muscular portions of the stomach, duodenum, jejunum, ileum, mesenteric vessels, hepatic portal vein and two arteries (carotid and aorta) was investigated in long term streptozotocin-induced diabetes mellitus (DM; fed ad libitum and pair fed). In all regions of the gastrointestinal tract there were no changes in PG synthesis (per unit weight of tissue) in diabetic rats (pair fed or fed ad libitum) compared to controls. However, there were marked increases in PG synthesis (up to 3 fold) by the mesenteric vasculature and hepatic portal vein in diabetic animals fed ad libitum and in pair fed diabetic rats and decreases in the aorta and carotid artery. These data suggest that increases in PG synthesis by the splanchnic vasculature may constitute a specific adaptive response to DM. The similarity of the responses of pair fed rats to those of rats fed ad libitum indicates that DM and not hyperphagia is the likely determinant of these adaptive changes. Given that increased splanchnic blood flow enhances nutrient uptake (both known to occur in DM), the increase in splanchnic vascular PG synthesis, in particular of vasodilatory PGI2, may contribute to enhanced nutrient uptake.


The glgB gene from the thermophile Bacillus caldolyticus encodes a thermolabile branching enzyme. We have cloned the structural gene for the Bacillus caldolyticus glycogen branching enzyme (glgB) in Escherichia coli. The glgB gene consisted of a 1998 bp open reading frame (ORF) encoding a 78,087 Da protein, which was highly similar to the Bacillus stearothermophilus branching enzyme. The 5' end of a second gene that encoded a protein with extensive similarity to E. coli ADP-glucose pyrophosphorylase (ADPGP) partly overlapped the 3' end of the glgB gene. A putative promoter recognized by Bacillus subtilis RNA polymerase containing the sigma factor H (E-sigma H) preceded the genes. These data suggest that in contrast to the situation observed in B. stearothermophilus, the genes involved in glycogen synthesis in B. caldolyticus are clustered on the chromosome, and are presumably coordinately expressed during the early stages of sporulation. An incomplete third gene started upstream of B. caldolyticus glgB. This gene was highly similar to a gene found directly upstream of B. stearothermophilus glgB, which encodes a putative membrane protein with unknown function. The B. caldolyticus glgB gene was expressed in E. coli and B. subtilis. Surprisingly, the branching enzyme appeared to be thermolabile, the temperature of optimal activity being only 39 degrees C.


Cloning and sequencing of human kappa-casein cDNA. A cDNA encoding kappa-casein of human milk was cloned and sequenced. The kappa-casein cDNA was isolated from a lambda gt11 library generated from mRNA prepared from a mammary gland biopsy obtained from a lactating woman. The library was screened with polyclonal rabbit antibodies raised against purified native kappa-casein. The obtained nucleotide sequence contained an ORF sufficient to encode the entire amino acid sequence of a kappa-casein precursor protein consisting of 182 amino acids. This includes a tentative signal peptide of 20 amino acids and a processed protein of 162 amino acids.


Nucleotide sequence of a Drosophila melanogaster gene encoding a calreticulin homologue. A Drosophila melanogaster gene encoding a homologue of the mammalian ER calcium binding protein, calreticulin, was cloned and the nucleotide sequence determined. Four exons can be identified, contained within 1700 bp of sequence, separated by introns of 124, 266 and 92 bases. The exons encode a 389 amino acid protein which may be a precursor form as it includes an N-terminal signal region of 17 residues that could potentially be cleaved to form a mature protein. The C-terminal region of the protein contains the established pattern of polyacidic clusters, common to calreticulins of other species and ends in the ER retention signal HDEL. Excluding the N-terminal signal region, the Drosophila protein amino acid sequence has a 67% identity to mammalian calreticulins and the length and acidity of the C-terminal zone in the insect protein are intermediate between higher mammalian and lower nematode values.


Isolation of different brain-specific isotypes of alpha-tubulins from chum salmon (Oncorhynchus keta). An alpha-tubulin cDNA clone, pTUB5 (1496 bp), encoding a protein of 444 amino acids (mol. wt. 48,840), has been isolated from the brain of Pacific salmon, Oncorhynchus keta. Partial sequence data were also obtained for two other alpha-tubulin isotypes, pTUB6 and pTUB9, which are similar in sequence to pTUB5 except in the carboxy region of the protein. This region of alpha-tubulin has previously been shown to be important for the binding of microtubule associated proteins suggesting that the isotypes described in this study may represent differentially controlled elements of the neural tubulin population. The isotypes show brain-specific expression and are the first tubulins to be reported for this tissue in fish.


Nucleotide sequence of the mitochondrial 5S rRNA gene from lupine (Lupinus luteus). A lupine mitochondrial clone containing 5S rRNA gene is characterized. The gene is located on the same strand as 18S rRNA and separated from it by 190 nucleotides. The intergenic region in different plants shows high degree of homology. In the case of lupine and soybean 43 nucleotides upstream of 5S rRNA gene exhibits 100% of homology. Comparisons of lupine 5S rRNA gene sequence with other plant mitochondrial 5S rRNA genes displays high degree of homology (from 89.8% to 95.8%).


Utilization of rat and human sera to carry out incubation and perifusion of pancreatic islets. Incubation of isolated pancreatic rat islets in a medium consisting of fresh rat or human sera and the measurement of insulin secretion after 60 min in the presence of 6.0-7.0 and 16.7 mM of glucose, were carried out. Perifusion experiments with isolated rat islets preincubated in the presence of rat or human sera and 0.2 mCi/mL of 45Ca2+ were also performed, and 45Ca2+ outflow rate and insulin secretion were analyzed. In both experiments, the usual islet responsiveness to glucose stimulation was preserved when compared with experiments in which Krebs-Henseleit (K-H) buffer was used as the medium. The results obtained demonstrate that both rat and human sera can be used as media for islets perifusion and incubation experiments, thus allowing for the effect(s) of circulating substances on insulin release to be examined.


Administration of the anesthetic isoflurane to mice: a model for acute intermittent porphyria? The effects of isoflurane, a commonly used volatile anesthetic, on the activity of some haem enzymes in liver, kidney, and blood, and glucose content in liver and blood were studied. Mice were injected with different doses of the drug (0.5-6 mL/kg) and killed at varying intervals after injection (5-240 min). Within this dose range, optimal effects on alteration of haem metabolism were obtained at 2 mL/kg. The time-response profile for each enzyme was different. Blood porphobilinogenase (PBGase) and deaminase showed lower activities 20 min after anesthesia. This diminution coupled with the induction of delta-aminolevulinate synthetase activity observed soon after anesthesia (5 min) would fit well with the expected biochemical changes occurring in acute intermittent porphyria, indicating that this may be a suitable animal model for this disease.


Effects of milrinone on lung water content in dogs with acute pulmonary hypertension. To evaluate the effects of milrinone (MIL) on hemodynamics and lung water content, we used 10 mongrel dogs with pulmonary hypertension (PH). To induce pulmonary hypertension, we administered two injections of glass beads stirred in saline to dogs. Mean pulmonary arterial pressure (PAP) and pulmonary vascular resistance significantly increased following induction. Milrinone, which inhibits cyclic AMP phosphodiesterase-(PDE) demonstrated pulmonary vasodilation, indicated a reduction in these two parameters. To clarify the drug mechanism, we measured lung water content as extravascular lung thermal volume (ETVL) using a thermo/sodium double-indicator dilution method. The induction of pulmonary hypertension produced a transient reduction in extravascular lung thermal volume. The parameter remained constant following milrinone administration, whereas the control showed a gradual increase. Of the 10 dogs, five were killed to measure gravimetrically the volume of lung water content as a comparison with extravascular lung thermal volume. We concluded that milrinone produced pulmonary vasodilation which induced a reduction in the transmural capillary pressure gradient according to Starling's hypothesis. This study suggests that the reduction in the transmural pressure gradient induced by milrinone may also prevent the re-elevation in extravascular lung thermal volume. Milrinone increases the cyclic AMP level in the endothelium and in the platelet which may affect either directly or indirectly the permeability of capillary endothelium.


Analysis of concentration-response relationships by seemingly unrelated nonlinear regression (SUNR) technique. In performing statistical evaluation of concentration-response relationship in pharmacological studies, all the commercially available statistical packages assume each data point is an independent measure of the drug response, and do not account for the dependence between the multiple measurements taken from the same subject (tissue, animal, or sample). Seemingly unrelated nonlinear regression (SUNR) is a statistical technique that takes into account both within-and between-subject variance. This technique has been implemented in an SAS-based interactive program called SUNR. The statistical analyses are based upon the original work by Gallant (Gallant, 1975, J Econometrics 3:35-50; Gallant and Goebel, 1976, JASA 71:961-967), which has been further developed by Muller and Helms (1984) (Presented at ASA meeting in Washington, D.C.) To test this program, we have analyzed both simulated and actual data with SUNR, comparing our results to those of several popular statistical programs. All the programs yielded essentially the same estimates for the EC50, minimum and maximum response in both the simulated and experimental data sets. However, our results differed markedly from the commercial packages in the estimates of standard errors associated with the estimated maxima. When analyzing simulated data, which were far less noisy than the experimental data, differences between the analyses were minimal. However, in the analyses of experimental data, the standard errors calculated by the commercial programs appear to significantly underestimate the standard error. Using SUNR, however, the 95% confidence limits on the maxima are markedly wider, and, importantly, always cover the observed actual data range.


Efficacy of various water-soluble chelator molecules in the liposome-mediated macrophage "suicide" technique. In earlier studies, we described a technique for the "in vivo" depletion of macrophages, using liposome-encapsulated dichloromethylene bisphosphonate (C12MBP). The aim of the present study was to compare the effects on macrophages of various other liposome-delivered Ca2+ chelators: EDTA, DTPA, and EGTA. It appeared that both EDTA and DTPA as well as Ca(2+)-and Cu(2+)-EDTA complexes were also effective in the elimination of splenic macrophages when encapsulated in liposomes and intravenously injected. EGTA, a well-known and frequently used Ca2+ chelator, had no effect.


Method for study of endothelium-dependent vasodilatation in rabbit intrarenal arterial network. The objectives of this study were twofold: 1) to determine whether a microdissected rabbit intrarenal arterial network (IAN), consisting mainly of interlobar, arcuate, and interlobular arteries exhibits endothelium-dependent vasodilatation, and 2) to establish a means of selectively abolishing this response. The IAN was perfused at a constant flow with heated-oxygenated Krebs-bicarbonate buffer through the main renal artery, and evoked responses were limited to vessels distal to the renal artery. A decrease in perfusion pressure reflected a vasodilator response, after vascular tone had been induced by intraarterial infusion of phenylephrine. Bolus injections of acetylcholine produced graded endothelium-dependent vasodilator responses, whereas glyceryl trinitrate caused endothelium-independent responses. Manual de-endothelialization was accomplished by gently stroking the IAN and at the same time removing any remaining glomeruli. This procedure blocked the response to acetylcholine, but not to glyceryl trinitrate (n = 6). A 10-min infusion of NG nitro-L-arginine (NArg) (4 x 10(-5)-3 x 10(-4) M) into the IAN also selectively attenuated the response to acetylcholine (n = 7). The third procedure, consisting of a 10-min infusion of 22-44 mM hydrogen peroxide into the IAN also attenuated the response to acetylcholine, but not to glyceryl trinitrate in nine of 12 experiments. This investigation demonstrates that intrarenal arteries are capable of undergoing endothelium-dependent vasodilatation, and the potential use of the IAN for further study of renal endothelium-derived vasoactive factors.


[The management of the development of occupationally important qualities for the purpose of improving the training of flight personnel]. The issues of purposeful development of occupationally important qualities (OIQ) of the pilots using a specially devised set of psychological, pedagogical, psychophysiological methods are studied. Evidence for an effect of the applied methods on the development of OIQ, success and reliability of flying activity is presented. Some mechanisms of creating an integral system of OIQ during pilot training are discussed. The peculiarities of OIQ influence on specific aspects and parameters of pilot activity including a real flight are considered. The views on the patterns of creating the professional flying abilities, their place in the structure of a pilot fitness for flying are discussed.


[Age-related changes in the hemoglobin concentrations and erythrocytes of pilots]. Longitudinal retrospective study has revealed the changes in the health of 706 pilots and air navigators and in the hemoglobin (Hb) and erythrocyte levels in peripheral blood once within a 5 year period. The duration of an examination is 10 years and even longer. It is established that the Hb concentration increased with an increase of the age. At the age of 20-30, this parameter is lower in persons being healthy for a long time. An analysis based on curve plotting of the remainder of life time indicated that the high level of Hb and high mean concentration of Hb in the erythrocytes have an adverse effect on the health and flight fitness. The regularities are noted within the normal values and validate a differentiated approach to evaluating the results of diagnostic examinations instead simplified normal-non-normal estimates.


[Psychosomatic status and the quality of the piloting in flyers during geomagnetic disturbances]. After using the psychological tests, namely Minnesota Multiphasic Personality Inventory (MMPI) and Luchaire 8-color test, a large group of pilots was divided into the individuals with high and low levels of anxiety. The highly anxious persons as opposed to those with a low level of anxiety are characterized by a more anxious level of operating during the quiet days free from magnetic disturbances. On heliogeomagnetic exposures, the pilots with a high level of anxiety unlike those with a low anxiety level operate at a new, even more intensive homeostatic level which is accompanied by a decreased functional activity of the central nervous system. The latter leads to a sharp decline in flying skills. Since there have been no significant changes in the physiological status and flying skills of the pilots with a low anxiety level during magnetic disturbances, it should be considered that the high level of anxiety is the risk of heliometeolability and flight safety. The ways to correct the high level of anxiety are developed.


[The characteristics of the action of ethanol in operators with different states of the skin tissue basophils]. The changes in some parameters of an operator activity after ethanol administration at a dose of 1.9 g/kg body weight in 10 men doing the job of two-dimensional compensatory tracking in simulator, have been studied. In this case, the population state of tissue basophils (mast cells) of the body by studying the amounts of various structural and metabolic forms of these cells, contained in the skin biopsies, was studied. The degree of deterioration in operator activity was evaluated separately for the subjects with the population characteristics of tissue basophils higher or lower than mean values. It is indicated that the subjects with a low initial number of tissue basophils exhibiting signs of a holocrine-typed secretion and with a more pronounced response of these cells to ethanol were characterized by a significantly higher degree of the impairing many parameters of operator activity. Such differences were especially marked immediately after ethanol administration and practically lacked 12 hours after.


[The circadian rhythmicity of human orthostatic tolerance]. The results of studying the daily rhythmicity of orthostatic tolerance of blood system in practically healthy men are presented. The orthostatic test was performed 6 times a day with a 4-hour interval. The parameters of systemic, cerebral and peripheric hemodynamics have been recorded. It is found that a degree of a change in an intensity of cerebral blood supply experiences the marked variations depending on time of day. The day-night cycling of orthostatic tolerance of cerebral circulation is greatly determined by the biorhythm of the responses of arterial vessels of the lower extremities, i.e., by the natural periodization of blood redistribution processes. The highest orthostatic tolerance is noted at 3 to 11 a.m. and the lowest one at 3-7 p.m.


[Human blood biochemical parameters under the conditions of an arid zone]. Seven participants of 23 day walking march in an arid environment have been examined. Biochemical analysis of blood serum made on Day 2 of marching revealed a decrease in the levels of glucose, triglycerides and an increase in the concentration of non-esterified fatty acids which the authors characterize as the state of moderate stress in an acute period.


[Metabolism in cosmonauts: the results of biochemical research on the blood of the crew members of the 7 prime expeditions on the Mir orbital space complex]. The pre- and postflight biochemical analyses of the blood of 16 cosmonauts flown aboard Mir orbital station over 125-366 days revealed the changes in carbohydrate, lipid and protein metabolism being in line with the present-day ideas about the space flight effects on the human metabolism. A particular individual pattern of the responses and the absence of correlation with flight duration of space expeditions ranging from 4 months to a 1 year, are noted.


[Microwaves and the visual analyzer].

[Microwaves and the visual analyzer]. The results of studying an effect of microwaves on the different regions of visual analyzer are investigated. The morphofunctional changes at the light-optic and electron-microscopic levels are revealed. The changes involve not only peripheric area of visual analyzer but also its central regions. Some epidemiologic observations are indicative of: altered sizes of blind spot; decreased magnitudes of optic rheobase and chronaxy; color vision disorder; increased diastolic pressure in central artery of the retina. Study of bioelectrical activity of the retina enabled some investigators to make a conclusion about a reaction disorders occurring in the subcortical visual centers. It is noted that the animal studies not always explain unequivocally the microwave effects on the visual analyzer.


[The effect of moderate altitude on the maintenance of a good health status and high physical work capacity in cosmonauts over the course of a long period of time]. The development of the methods to maintain good health and high performance and occupational longevity of cosmonauts is an urgent problem. For this end, an effect of periodic (1-2 times a year) training in mid-lands on working and functional capacities of cosmonauts being members of cosmonauts corps for extended periods of time (20 years) was studied; the results of 40 trainings in mid-lands at 1,600 to 2,400 m above sea level are summarized. Before, during and after training, the physiological and physical parameters of the body (BP after Korotkoff, HR, VO2max) during exercise bicycle ergometer tests as well as the time of running on treadmill at a rate of 4.5 m/s to failure have been examined. The experimental findings indicated that after terminating physical training in mid-lands the major group of test subjects exhibited a significant decrease in HR as compared to the control value. During acclimatization, the arterial pressure (systolic and diastolic) measured when exercising on bicycle ergometer at 600 and 1000 kgm/min also reduced. As a result of improving the measured parameters after acclimatization to mountain environments the total body tolerance increased. A cumulative effect of the regular stay in mid-lands appears to change VO2max which did not decrease in man with age and the performance value (after i.v. Aulik classification) in the 40-49 age group subjects became very high.


[Vestibulo-oculomotor reactions during immersion hypokinesia]. The results of studying the spontaneous oculomotor responses and those induced by vestibular and visual stimulation in 30 test subjects exposed to a 3-day dry immersion are presented. The subjects were tested every day under conditions of free diving and during additional tactile-proprioceptive, optokinetic and vestibulo-optokinetic stimulation. It is indicated that an exposure to immersion is inherent in an increased amplitude and rate of spontaneous floating movements of the eyes and in 30 percent of cases in: developing of spontaneous nystagmus; decreasing of an accuracy of fixed turns and tracking; facilitating of oculomotor responses during optokinetic and optovestibular stimulation. When used an additional support, on Day 0-1 after optokinetic and optovestibular stimulation on Days 2-3 of immersion the tested oculomotor responses were improved.


[The humoral immunity indices of rhesus monkeys under the action of extreme factors in space flight]. Some features of nonspecific resistance of rhesus monkeys (G and A immunoglobulins and C3 complement component) are studied. Standards of IgG, IgA and C3 complement component in healthy rhesus monkeys are determined. The changes in the parameters of nonspecific resistance of the animals in all stages of their preflight training and shortly after flight experiment are examined. These alterations were appeared first of all as an increase in IgA level.


[The hemodynamics in monkeys during head-down tilt hypokinesia at angles of -6 and -20 degrees]. Hemodynamic changes in the monkeys (2 groups of 3 animals each) during 6 degrees and 20 degrees head down tilts (HDT) of various duration have been studied. An increase of the arterial blood pressure and linear velocity of the blood flow in the common carotid artery was noted immediately after HDT followed by a compensatory decrease of the values. A significant decline in orthostatic tolerance after 20 degrees HDT with developing a precollaptoid state is indicated. The changes of a circulation pattern in the common carotid artery bed are induced by a cranial shifting of the body fluids.


[The dynamics of the central and peripheral blood circulation in waking rats in the first 24 hours of head-down tilt hypokinesia (the role of training)]. The male Wistar rats were used to study an effect of preliminary antiorthostatic training on the systemic and regional hemodynamics during 24-hour head down tilting (HDT). It is indicated that the main parameters of the systemic hemodynamics (arterial blood pressure, heart rate, central venous pressure, total peripheric resistance, systemic veins) in trained animals were changed to a lesser extent as opposed to the controls. The dynamics of the mean pressure of blood filling--a parameter responsible for the state of systemic veins of the body--was group different. The blood flow changes in the organs and tissues were tended to be the same, however these changes were less severe in the trained rats. Thus pretraining of the rats, not changing the general trend of the shifts in the recorded values, decreases the severity of their variations.


[The combined action of head-down tilt hypodynamia and gamma irradiation on higher nervous activity in rats]. The paper deals with a combined effect of 30-day HDT and gamma radiation at a dose of 3 Gy on the higher nervous activity of the experimental rats. In the rats, the immobilization and isolation stresses induced by HDT are found to cause the development of pathologic aggressive reaction with the disorder of a species-typical pattern of an aggressive act and long-term change in animal social relations. The 30-day HDT disturbs the process of forming the motor-drinking differentiated conditioned reflex coming to a reduction of internal inhibition, generalization and sluggishness of a stimulation process. Functionally, these processes are reflected by a behavioral pattern shifting to stable stereotype impeding the formation of differentiated inhibition. Against HDT the unidirectional gamma radiation exposure increases this effect. In some cases, it leads to blocking the adaptational processes showing in the development of neurotic responses or deep, beyond the limits, inhibition.


[The healing of bone fractures in rats during the readaptation after a 14-day head-down suspension]. Histological, histochemical and histomorphometric methods have been used to study an effect of a 14-day head-down suspension on healing the fractured fibular diaphysis in the rats traumatized immediately after suspension. The study of the fibulae on Days 11 and 17 following an operative fracture indicated that both in control and experimental rats the ends of fractured bones were tightly interconnected by the calluses. A comparative study of the calluses and their structural components as well as detailed investigation of histological structure of calluses on the 11th and 17th post-traumatic days did not reveal significant differences between control and experimental animals. Furthermore, the rate of cartilage replacement by spongy bone tissue in calluses of experimental animals was even somewhat higher than that in control rats. Thus the data obtained give ground to believe that in a readaptation period after 14-day suspension resulting in the osteoporotic changes of weight-bearing bones a repair process in the bones is rapidly normalized and in some parameters exceeds it in control animals.


[Ultrastructure of the myocardium in the calcium channel blocker withdrawal syndrome]. Changes in the ultrastructure of rat myocardial cells were investigated after withdrawal of therapy with the calcium entry blockers diltiazem, nifedipine, and verapamil. Two hours after the last administration the ultrastructure was without significant changes in comparison to the control group. However the incidence of contracture bands, dehiscence of intercalated discs and lesions of mitochondria observed 30 hours after therapy withdrawal demonstrated serious damage of myocardial tissue. The recorded changes, practically identical with changes associated with the calcium paradox, were the consequence of withdrawal of calcium entry blocker therapy. The reported morphological changes reflected biochemical and functional changes characteristic of the calcium entry blocker withdrawal syndrome.


[The effect increased choline levels on the synthesis and release of acetylcholine in heart atria in white rats]. The paper addresses the problem of (1) the relationship of choline in extracellular fluid and acetylcholine (ACh) synthesis in chambers of the heart of white rats, and (2) the possibility of physiological involvement of this ACh in the control of cardiac activity. Within 60 min after s.c. administration of choline in the dose of 300 mg/kg body weight the ACh content rose to 136% of the control value in isolated heart chambers and after administration of 400 mg/kg body weight to 159% of the control value. Increased ACh synthesis failed to affect the heart rate, nor did it increase the tonic effect of vagus innervation of the heart. Excessive ACh could however be released by electric transmural stimulation of isolated heart chambers as well as by potassium depolarization. The release depended on the presence of calcium ions. The obtained results demonstrate that an increase in the level of choline in extracellular fluid results in increased ACh synthesis in nerve terminals. Enhanced release of this ACh is a precondition for high choline levels to induce an increase in parasympathetic control of cardiac function.


[Familial supravalvular aortic stenosis]. By means of two dimensional echocardiography supravalvular aortic stenosis was diagnosed in two siblings and their cousin. Autosomal dominant transmission with incomplete penetrance or even non-penetrance is assumed to be involved. Somatic stigmatization, typical for Williams' syndrome, failed to be present in the affected children. The reported family provides further evidence that familial supravalvular aortic stenosis and Williams' syndrome are two distinct clinical entities. (Tab. 1, Fig. 3, Ref. 23.)


[Isolated arteritis of the central nervous system]. Isolated arteritis of the central nervous system (CNS) is a relatively rare condition. Of the patients treated at our department two presented with characteristic features and eventually the diagnosis of isolated arteritis of the CNS was established. Headaches and relapsing lesions of cerebral nerves were predominant in the clinical picture of the first patient. In agreement with the clinical picture suggesting that small arteries were affected, the angiographic (AG) finding was negative and the diagnosis was based mainly on the positive effect of immunosuppressive treatment. The second patient with relapsing monofocal brain damage had a typical AG finding and a positive response to the treatment. The clinical picture of isolated arteritis of the CNS can be rather varied, with headaches and different neurological features being predominant. Both AG and bioptic examinations may prove negative. Positive response to immunosuppressive treatment is to be considered a characteristic feature of the disease. (Fig. 3, Ref. 11.)


[Precancerous and malignant tumors of the uterine cervix]. Bioptic findings recorded in 366 women with lesions of the endocervix and exocervix were analyzed in a retrospective study covering the years 1988 to 1990. The series represented 24.5% of the total number of 1495 gynecological precancerous and tumorous changes. Severe dysplastic changes and malignant tumors of the endocervix were seen in 31 patients (19.4%). Concurrence of endocervical and exocervical lesions was recorded in 66 patients (18.0%). In the studied series 35% of the women were below the age of 40 years. Signs of koilocystic dysplasia were recorded in 72 women (37%) with precancerous and tumorous lesions. (Fig. 4, Ref. 15.)


[The ecological-morphological characteristics of the growth and distribution of cultures of single-cell organisms in a gravitational field]. The paper analyses and summarizes the experimental results obtained by the authors and data accumulated in the literature during recent years in order to reveal the general regularities of the growth, distribution and behavioral parameters of the cells under conditions of reduced gravity ranged from 10(-5) to 5 g. It is indicated that an intensity of gravity effect on these parameters of unicellular organisms depends greatly on the environments, types of cells and their metabolic levels. The effects of changed gravity at the cellular level are the result of shifting the primary physiological characteristics and physicochemical parameters of the culture and cell environments as an integrated biological system.


[Biological effects of selenium].

[Biological effects of selenium]. The role of selenium concerning its biological effects particularly in relation to cardiovascular and tumor diseases has been in the focus of intensive studies. Selenium is a constituent part of the enzyme glutathion peroxidase (E.C.1.11.1.9) which catalyzes the conversion of hydrogen peroxide and organic hydroperoxides into water and corresponding alcohols. A review of epidemiological studies is presented focusing predominantly on countries where a low concentration of selenium in blood serum was found. The role of selenium in the etiology of cardiovascular diseases may probably be accounted for by its protective effect as it prevents platelet aggregation and protects the arterial endothelium from being damaged by lipid peroxides. The results of experimental studies, carried out in research institutes in many parts of the world, suggest that coordinated supplementation of food with selenium may reduce the risk of cancer and moreover, the effect of selenium can be modified by other dietary factors, such as vitamin A and E. (Fig. 2, Ref. 29.)