Urinary type IV collagenase: elevated levels are associated with bladder transitional cell carcinoma. Accumulating experimental evidence has linked the overproduction of extracellular matrix-degrading metalloproteinases with tumor cell invasion. In the present study one member of the metalloproteinase family, type IV collagenase (M(r) 72,000 gelatinase), is shown to be elevated in the urine of patients with transitional cell carcinoma of the bladder. The form of the enzyme in the urine was studied by three independent methods: enzyme-linked immunosorbent assay, Western immunoblotting; and gelatin zymography. Immunoblotting revealed that the enzyme was present as a series of fragments, each retaining the amino terminus of the mature proenzyme. A prominent M(r) 43,000 fragment was associated with the transitional cell carcinoma cases. Zymography demonstrated that multiple enzyme species with gelatinase activity were present in urine and that high-molecular-weight bands of substrate lysis corresponded to complexes between type IV collagenase and tissue inhibitor of metalloproteinases 2. The total amount of type IV collagenase antigen was significantly elevated in the urine of 37 transitional cell carcinoma patients (range, 0-1081 ng/ml; mean, 318.4 +/- 147.3) compared to 19 normal controls (P < or = 0.004) and 17 inflammatory disease controls (P < or = 0.011). Immunohistochemical staining of bladder tumor biopsies verified that the transitional cell carcinoma cells were producing the M(r) 72,000 enzyme. Thus, M(r) 72,000 type IV collagenase, which is present in the urine in many forms including fragments and complexes with inhibitors, may be a useful marker for bladder cancer diagnosis or prognosis.


Type IV collagenase/gelatinase (MMP-2) is not increased in plasma of patients with cancer. We have developed a sensitive and specific sandwich-type enzyme-linked immunosorbent assay to detect M(r) 72,000 type IV collagenase [matrix metalloproteinase 2 (MMP-2)] in human plasma. As a result of the linkage between MMP-2 production by cancer cells and the metastatic phenotype, we undertook this study to compare plasma MMP-2 levels in healthy individuals, patients with various types of cancer, and hospitalized patients with chronic diseases other than cancer. The results demonstrate that MMP-2 levels are not increased in cancer patients regardless of the extent of disseminated malignancy. In an effort to explain this data, we compared MMP-2 secretion by human umbilical vein endothelial cells and lung cancer cells passaged as cell lines. Endothelial cells secreted higher levels of MMP-2 than did lung cancer cells propagated in vitro. We propose that blood vessel lining cells make a sizable contribution to plasma levels of MMP-2 and may thereby obfuscate the detection of increased levels of MMP-2 originating from extravascular sources such as solid tumors.


Allelic frequency of a p53 polymorphism in human lung cancer. p53 is a tumor suppressor gene that is mutated in diverse tumor types. Here we report the frequencies of common polymorphic variants at codon 72 of the p53 gene in germline DNA of lung cancer cases and controls as determined by a polymerase chain reaction strategy. The observed allelic distribution was found to be significantly different between African-Americans and Caucasians in this U.S. population. The frequency of polymorphic variants was similar in lung cancer cases and controls after adjustment for race. However, among lung cancer patients the proline variant at codon 72 was in excess in adenocarcinoma patients by comparison with other histologies.


Characteristics of women by smoking status in the San Francisco Bay Area. To better understand why smokers are more likely to develop cervical cancer than nonsmokers, we investigated laboratory and demographic differences between the two groups. Women between the ages of 18 and 49 who attended eleven community clinics in the San Francisco Bay Area were studied to investigate differences between smokers and nonsmokers. The 332 smokers and 365 nonsmokers were queried about smoking habits, sexual and reproductive history, and recent diet. Cervical mucus specimens were cultured for yeast, lactobacillus, and other microorganisms. Results showed that white Hispanic women were less likely to smoke than white non-Hispanic women. Smokers, when compared to nonsmokers, consumed larger quantities of coffee, soft drinks, liquor, and beer in the 24 h prior to the interview. Women who smoked were more likely than those who did not smoke to have had first sexual intercourse before age 16, had a greater number of lifetime sexual partners, and were more likely than nonsmokers to have been pregnant. After controlling for number of sexual partners, smokers reported a history of chlamydia, gonorrhea, and/or pelvic inflammatory disease more often than did nonsmokers, and cervical mucus of smokers was more likely than that from nonsmokers to contain greater than 8500 microorganisms/ml.


Host factors in lung cancer risk: a review of interdisciplinary studies. Host-specific factors influence risk for lung cancer. A few case-control and family studies of lung cancer susceptibility allowed for known lung cancer carcinogens and showed strong familial clustering with some evidence for a codominantly acting major gene. Cytochrome P-450 enzymes (e.g., CYP1A1) activate many carcinogens in tobacco smoke but have shown inconsistent associations with risk for lung cancer. Case-control studies that assess the effects of CYPIID6 on lung cancer risk have consistently shown a mildly decreased risk for lung cancer among poor metabolizers. Cell surface markers have shown little relation to risk for lung cancer. Studies involving DNA or hemoglobin adducts, sister chromatid exchange, or oncogene activation only indirectly measure host-specific risk, and these assays have suffered from poor reproducibility and high cost. We describe epidemiological designs to assess specific genetic factors that may alter lung cancer risk.


A case-control study of the etiology of Ewing's sarcoma. An interview case-control study was undertaken to search for risk factors for Ewing's sarcoma. The 208 cases, aged 5 months to 22 years at diagnosis and all white but one, were identified from hospitals participating in the Intergroup Ewing's Sarcoma Study therapeutic trials. Two controls were sought for each case: a sibling control and an age-matched regional population control identified through random-digit dialing telephone procedures. A questionnaire was administered to the parents of cases and controls. Parents were more likely to have smoked during the pregnancy with the case than during the pregnancy with the unaffected sibling. Risks rose with the number of cigarettes the mother smoked per day during the pregnancy. Concepti exposed to less than 1 pack/day were at 3.2 times the risk, and those exposed to 1 pack or more were at 6.7 times the risk of the nonexposed. However, risks associated with smoking were lower and not statistically significant in analyses using the region-matched controls. Hernias, mostly umbilical and inguinal, were diagnosed six times more frequently among the cases compared to region-matched controls. However, hernias occurred in just 10% of cases, and the matched siblings had hernias diagnosed with the same frequency as the cases. An apparent excess of heart disorders among cases versus siblings seems likely to be an artifact of increased medical surveillance of cases.(ABSTRACT TRUNCATED AT 250 WORDS)


Medical history and the risk of non-Hodgkin's lymphomas. The relationship between selected aspects of medical history and the risk of non-Hodgkin's lymphomas (NHLs) was investigated using data from a hospital-based case-control study conducted in northern Italy on 177 cases of NHL and 561 controls in hospital for acute conditions, other than nonneoplastic or immunological. Among six viral diseases considered, only herpes zoster (shingles) had a relative risk (RR) significantly above unity [RR = 2.7; 95% confidence intervals (CI), 1.5 to 4.7]. The association, however, was restricted to subjects whose diagnosis of herpes zoster dated back to less than 10 years, suggesting that this slow-acting virus could be reactivated by the early development of NHL. Six of eight bacterial diseases considered showed RR above unity, and the estimate was significant for scarlet fever (RR = 1.9; 95% CI, 1.1 to 3.5) and pyelonephritis (RR = 5.3; 95% CI, 1.8 to 16.2). These associations were not restricted to the few years before lymphoma diagnosis. When various classes of infectious or inflammatory diseases were grouped together, no association was evident for viral infections (RR = 0.8; 95% CI, 0.6 to 1.2), acute bacterial diseases (RR = 1.0; 95% CI, 0.7 to 1.5), or allergic conditions (RR = 1.0; 95% CI, 0.6 to 2.1). The risk estimates were nonsignificantly above unity for chronic bacterial diseases (RR = 1.2; 95% CI, 0.7 to 1.2) and autoimmune conditions (RR = 1.4; 95% CI, 0.9 to 2.2), and significantly elevated for chronic inflammatory disease (RR = 1.9; 95% CI, 1.2 to 3.0).(ABSTRACT TRUNCATED AT 250 WORDS)


Association of serum ferritin levels with the risk of stomach cancer. A group of 5908 men provided serum samples during their study examination from 1967 to 1970. After a surveillance period of over 20 years, 121 incident cases of tissue-confirmed gastric cancer were identified. Their stored sera and those of 121 matched controls from the study population were tested for serum ferritin and transferrin levels. Because of the suggested effects of previous thawing on the serum results, detailed data analyses were limited to the 46 cases and matched controls whose sera were never thawed before this study. The mean serum levels (In ng/ml) were 5.26 for the 46 gastric cancer cases and 5.68 for their controls (P < 0.01). For serum transferrin, the mean levels (mg/dl) were 249.8 for cases and 254.1 for controls (P = 0.53). The inverse association with serum ferritin, which reflect total iron body stores, was stronger for the 21 cases diagnosed within 15 years of examination (P = 0.02) than for the 25 cases diagnosed after 15 years (P = 0.15). The limitations of the study and the implications of its findings are discussed.


Immunohistochemical evidence of p53 overexpression in gastric epithelial dysplasia. Molecular abnormalities of the p53 gene in chromosome 17p may be among the most commonly observed in human cancer. Their role in gastric carcinogenesis is suggested by their frequent detection in invasive adenocarcinomas. To investigate the chronology with which these abnormalities appear in the gastric carcinogenesis process, the expression of p53 proteins was investigated in late stages of the process, namely dysplasia, and in superficial carcinomas. A polyclonal antibody, CM-1, against both wild-type and mutant proteins was applied to paraffin-embedded biopsy and gastrectomy specimens previously fixed in buffered formalin. Positive nuclear stain was obtained in 36.4% of 33 cases of gastric epithelial dysplasia, corresponding to 19% of mild, 27.3% of moderate, and 64.3% of severe dysplasias. Eight of 13 (61.5%) invasive carcinomas showed positive stain. The data indicate an increased incidence of p53 abnormalities in the late stages of gastric carcinogenesis.


Effects of breast cancer treatments on plasma nutrient levels: implications for epidemiological studies. The interpretation of case-control studies in which blood nutrient levels are examined as etiological factors in cancer is complicated by the possibility that either the disease or its treatment may alter these levels. Circulating levels of selected nutrients were examined prior to diagnostic biopsy and compared with levels 3 to 4 months after diagnosis among 71 women with breast cancer and 95 women with benign breast disease. Among women with benign breast disease or women with breast cancer who were not given postsurgical adjuvant drug therapy, levels of alpha-carotene, lycopene, alpha-tocopherol, cholesterol, and triglycerides did not change over time. In contrast, women who received chemotherapy had increased levels of cholesterol, retinol, and alpha- and gamma-tocopherol, and women on antiestrogen therapy showed increased levels of triglycerides and alpha-tocopherol. Overall, the concentrations of carotenoids (lycopene, alpha-carotene, and beta-carotene) did not change in breast cancer cases, although subgroup analyses showed increased levels of beta-carotene among cases not receiving drug treatment and decreased levels among those receiving antiestrogens. In summary, blood levels of some nutrients did not appear to be affected by breast cancer or its treatments, but changes were noted for levels of plasma lipids, tocopherols, retinol, and beta-carotene. Those investigating the etiological relationship between breast cancer and circulating nutrients need to consider these effects in designing and interpreting epidemiological studies.


Impact of a physician intervention program to increase breast cancer screening. In order to improve compliance with the National Cancer Institute's breast cancer screening guidelines, we developed a multifaceted intervention designed to alter physician screening practice. A pre-post test, two-community design was used. Primary care physicians in one community served as the control. Data were collected by two mailed surveys (1987 and 1990). Response rates were 61% and 64%, respectively. The physician intervention program consisted of a hospital-based continuing medical education program and an outreach component which focused on implementing a reminder system. Outcome measures were self-reported attitudinal, knowledge, and screening practices changes. In spite of an impressive change in comparison community physicians' practice, the difference in change over time in the intervention community physicians' ordering of annual mammography compared to the change in the comparison community physicians' ordering was significant (P = 0.04). The adjusted odds ratio is nearly 8. We conclude that our in-service continuing medical education program was successful in improving breast cancer screening practices among primary care physicians.


Breast self-examination proficiency and training effects: women at increased risk of breast cancer. While breast self-examination (BSE) frequency has received extensive research attention, proficiency has been less frequently addressed. Moreover, BSE proficiency among women at increased risk has not been adequately examined. Assessment of BSE proficiency is critical in determining the value of BSE with mammography and clinical breast examination in the early detection of breast cancer. BSE proficiency was assessed in 101 first-degree relatives of breast cancer patients. Participants were stratified by BSE frequency and randomized to one of two training techniques (MammaCare or concentric circle). BSE performance was assessed at baseline and at three follow-up visits at 4-month intervals. Proficiency was assessed by verbal description, a projected grid observational method, and lump detection ability on two breast models. BSE frequency was also assessed, in addition to BSE confidence, knowledge of breast cancer, risk perception, and worry related to breast cancer development. At baseline, proficiency was poor and correlations were not significant across assessment modalities. Significant improvement occurred on self-report measures, lump detection ability (true positives) on both models, and the projected grid. Improvement occurred across both training groups by the first follow-up, with no changes at subsequent visits. Both training techniques significantly improved BSE proficiency and were viewed positively by participants.


Apoptosis in the genesis and prevention of cancer. A strong rationale exists for developing cancer control strategies designed to suppress or reverse the development of precancerous lesions in order to reduce the occurrence and recurrence of this disease. Whereas numerous agents have been identified that inhibit tumor development, little is known about how they work. Recently the hypothesis has been raised that misregulation of apoptosis results in a failure of tissue size regulation that contributes to the development of cancer. If validated, this concept has important implications for the prevention of carcinogenesis and could lead to the development of new cancer control approaches that have as their basis the restoration of competence to regulate tissue size. Thus, it is essential to consider the role of cell loss in the tumorigenic process. In this regard investigation of the role of specific types of cell death in tumorigenesis, particularly the role of apoptotic cell death in maintenance of tissue homeostasis, has been neglected. The fact that apoptosis is a highly conserved, specific, and selective means of controlling tissue mass and shape also suggests that it can be exploited for the prevention or control of cancer.


Urinary 6 beta-hydroxycortisol/cortisol ratios measured by high-performance liquid chromatography for use as a biomarker for the human cytochrome P-450 3A4. Cortisol is metabolized to 6 beta-hydroxycortisol by the human cytochrome P-450 3A4, an enzyme implicated in the critical epoxidation reactions of aflatoxin B1 and certain polycyclic aromatic hydrocarbons. A method has been developed to measure the 6 beta-hydroxycortisol:cortisol ratio in human urine by reverse-phase high-performance liquid chromatography using diode-array detection. This method permits measurement of both cortisols in a single chromatographic run and has the potential to measure other metabolites useful for the determination of other human cytochrome P-450 activities. Using the 6 beta-hydroxycortisol:cortisol ratio as a marker of cytochrome P-450 3A4 activity adjusts for the circadian fluctuation in cortisol levels, providing a determination that is consistent over a 24-h period, obviating the need for 24-h urine collections. This high-performance liquid chromatography technique was used for the analysis of 14 different human urines and a range of ratios of 1.6 to 21.7 (mean +/- SE, 6.2 +/- 1.6) was found. These values are consistent with those reported in the literature. This method should be useful in molecular epidemiological studies investigating relationships between the susceptibility from environmental carcinogen exposure and cancer risk.


A prospective study of hprt mutant and mutation frequencies in treated cancer patients. We previously reported that some Hodgkin's disease patients had elevated hprt mutant frequencies in peripheral blood lymphocytes long after cessation of therapy. To determine if these elevations in mutant frequency represent true persistently elevated mutation frequencies, we recruited for a prospective study six previously treated Hodgkin's disease patients and five patients who had been treated for squamous cell carcinoma of the head and neck. These individuals were studied several times over a 6-7-month period. The results confirmed that a subset of patients have persistently high mutant frequencies when compared to 71 previously studied controls. The present study was designed to determine if the elevated mutant frequencies of treated patients represented independent mutations or resulted from the in vivo expansion of single mutant cells. We used the polymerase chain reaction to examine DNA single-strand conformation polymorphisms at the T-cell receptor gamma locus of individual mutant clones. This analysis showed that at any given time 20.1% of the mutants from Hodgkin's disease patients and 17.5% of the mutants from squamous cell carcinoma patients consisted of siblings, identified as having identical polymerase chain reaction/single-stranded conformation polymorphism patterns. The remaining mutants had unique polymerase chain reaction/single-stranded conformation polymorphism patterns and therefore can be presumed to have arisen from independent mutational events. Particular sibling mutants generally did not persist over time. However, one patient had one mutant clone which persisted but slowly decreased in prevalence over a 7-month sampling period. The data demonstrate that treatments for cancer result in persistently elevated mutation frequencies at the hprt locus in some, but not all, patients.(ABSTRACT TRUNCATED AT 250 WORDS)


High-risk coronary angioplasty using percutaneous cardiopulmonary bypass support. Balloon angioplasty has a high success rate but results in abrupt closure of the vessel in 2% to 6% of patients. This can lead to haemodynamic collapse and death, particularly if the patient has poor left ventricular function. In the event of abrupt closure of the coronary vessels, such patients may not survive long enough to undergo emergency bypass surgery. The prophylactic use of cardiopulmonary bypass to support patients at high-risk for angioplasty has been reported recently. We describe our initial experience with this technique. Eighteen high-risk patients with severe angina were subjected to balloon angioplasty after instituting percutaneous cardiopulmonary bypass support to enhance the safety of high-risk elective coronary angioplasty. All patients had a low ejection fraction, a large amount of viable myocardium perfused by the targeted artery or both (left ventricular ejection fraction < 25% in 13 patients). Triple-vessel disease was present in all of them. Angioplasty of the only remaining vessel was done in 12 patients, 2 vessels in 5 patients and a sequential graft in 1 patient. Bypass flow ranged from 2.8 to 4.5 litres and was discontinued after a mean of 35 minutes. Haemostasis was achieved by external clamp compression in 16 patients. The angioplasty was successfully performed in all the patients and was well tolerated. During the bypass period, the pulmonary artery diastolic pressure ranged from 0 to 8 mmHg. There was no hospital death. Two patients required surgical exploration of the femoral artery puncture site--one because of poor distal perfusion and the other for continued bleeding. During the follow up period of 1 to 10 months, 11 patients were free of angina and 1 had died. Our experience confirms that percutaneous bypass support in selected patients undergoing high-risk coronary angioplasty is safe and effective.


Impact of cigarette smoking on pulmonary function in non-allergic subjects. Cigarette smokers have been shown to have a greater tendency to develop respiratory allergies than non-smokers. Since the early obstructive airway changes seen in respiratory allergy and smoking are similar, the early airway changes seen in populations of young smokers might be attributed to the fact that a proportion of smokers are allergic. We therefore studied the effects of smoking on non-allergic individuals. Forced expiratory spirograms and peak expiratory flows were measured in a population of asymptomatic non-allergic male medical students, 59 smokers and 110 non-smokers. They had between 2 and 5 examinations performed serially over a period of 4 years. Smoking had a negative impact on pulmonary function. Analysis of covariance and multiple regression analysis using age, height gain and weight change as covariables showed that smokers, when compared to non-smokers, had a significantly greater percentage decline in the forced expiratory volume in one second expressed as a fraction of the forced vital capacity (4.01 +/- 4.6 v. 1.52 +/- 5.84), the forced expiratory flow in the middle half of the forced vital capacity (FEF25%-75%; 11.36 +/- 15.09 v. 5.3 +/- 17.58) and the ratio of the FEF25%-75% to the forced vital capacity (FEF/FVC; 14.06 +/- 14.45 v. 6.95 +/- 17.94). Our results suggest that young smokers, within a few years of starting to smoke, develop changes in pulmonary function indicating early peripheral airway narrowing, and that these effects worsen progressively with continued smoking.


Single daily dose of carbimazole in the treatment of hyperthyroidism. The antithyroid drugs, methimazole and carbimazole, are conventionally used in divided daily doses. However, these drugs have a longer intrathyroidal than a plasma half-life. We undertook this prospective, controlled study, in an area of mild iodine deficiency, to compare the efficacy of a single daily dose of carbimazole with divided doses in the treatment of hyperthyroidism. Nineteen patients with hyperthyroidism received 30 mg of carbimazole daily at bed time (group A) while 14 received 10 mg of carbimazole every 8 hours (group B). These patients were assessed clinically and biochemically by estimation of serum total thyroxine, total triiodothyronine and thyrotropin before and 1, 2, 3, 4 and 6 weeks after treatment. There was no significant difference between mean baseline concentrations of thyroxine and triiodothyronine. After 1, 2, 3, 4 and 6 weeks there was a decline in their concentrations which was similar in both groups (p > 0.05). Euthyroidism was achieved in 4.6 +/- 1.4 weeks (range 2-6 weeks) in group A and in 3.8 +/- 1.2 weeks (range 3-6 weeks) in group B (p > 0.05). We conclude that carbimazole in a single daily dose is an effective method for treating hyperthyroidism in an area of mild iodine deficiency and its efficacy is comparable to divided dose therapy. This practical and acceptable method of treatment can be specially useful in patients who find it difficult to remember to take divided doses.


Bacterial adherence to cotton and silk sutures. Silk and cotton sutures are the most commonly used materials for skin closure, the choice being largely based on tradition. We undertook this study to compare the bacterial adherence in vitro to these two materials because it is well known that the physicochemical characteristics of a suture material influence its ability to attract bacteria and consequently promote wound infection. We determined the bacterial adherence in vitro to cotton and silk for Staphylococcus aureus and Escherichia coli, common organisms found in postoperative infection at our institute, using three inoculum strengths. The sutures were incubated with the organisms and bacterial counts per suture material calculated after 20, 60, 120 and 180 hours of incubation. The bacterial counts for the sutures were then compared at these intervals. The bacterial adherence for both organisms at all time intervals was significantly greater to silk than to cotton, except at 60 hours for Staphylococcus aureus. The bacterial count for each suture material appeared to be an intrinsic property of the suture and did not vary with the concentration of the bacteria in the initial inoculum. The cost of an equivalent thickness of silk is 50 times that of cotton. We suggest that cotton should be the preferred suture for skin closure because bacterial adherence to it is lower and it is much cheaper than silk.


Molecular pathogenesis of chronic myelogenous leukaemia. Chronic myelogenous leukaemia is a clonal neoplasm of the pluripotent haematopoietic stem cell which is characterized in most patients by a consistent cytogenetic abnormality known as the Philadelphia chromosome. This chromosome occurs as a consequence of a reciprocal translocation between the long arms of chromosomes 9 and 22 which results in the creation of a new gene comprising sequences from the c-abl gene on chromosome 9 and the bcr gene on chromosome 22. The protein encoded by this structurally altered hybrid gene differs from the normal c-abl gene product in both molecular weight and in tyrosine kinase activity. It is likely that these alterations in the c-abl gene product play a central role in the pathogenesis of this leukaemia.


Environment and narcotics trafficking in Brazil. This study of the State of Rondônia in Brazil sheds light on how and why the cultivation of illicit narcotics crops and drug trafficking are affecting non-industrialized regions. It also highlights the negative impact of such activities on tropical ecosystems and human population.


Environment and drug trafficking.

Environment and drug trafficking. Illicit drug trafficking is a very complex matter, not only because it causes serious and pernicious problems in the socio-economic sphere, but because drug-taking can lead to personal degradation. To this situation, lamentable enough in itself, must be added the immense ecological and environmental damage, which presents grave and serious dangers for the planet.


Drug abuse control and the environment in northern Thailand. The ecology in northern Thailand has been affected by the lifestyle of minority groups living there and some ethnic Thai people. Since 1970 development work to improve socioeconomic conditions and national security has been under way. The highlands cover an area of 17 million hectares consisting of forest and watershed areas. A new problem has arisen with the spread of heroin abuse in the neighbouring Lao People's Democratic Republic and Myanmar, producing a negative impact on the ecology, politics and the administration of minority groups. The Government of Thailand has shown flexibility in striving to solve these problems through development work in cooperation with the private sector. This has contributed to good relationships between the countries concerned. Some of the policies and programmes introduced by the Government of Thailand are reviewed in this article.


Environmental impact of coca cultivation and cocaine production in the Amazon region of Peru. Little or nothing has been written about the environmental consequences of the cultivation of coca and the production of basic cocaine paste. Nevertheless, there is much evidence that both activities have a severe and irreparable impact on the ecosystems in which they are carried out. This chapter describes the situation in the Peruvian Amazon, discusses the consequences of these activities, and recommends measures to improve current conditions.


Illicit narcotics cultivation and processing: the ignored environmental drama. Drug abuse and the environment are among the most preoccupying issues in today's world. Up to now, relatively little attention has been given to linkages between these two issues, which are at first glance unconnected in any meaningful way. More careful analysis identifies major linkages between the environmental impact of illicit drug cultivation, the rapid expansion of illicit cultivation into tropical forest areas, the efforts to eradicate illicit crops and pollution through the processing of raw materials into drugs of abuse. This article reviews those linkages and recommends measures that might be taken to deal with their consequences.


Serotonin receptor 1c gene assigned to X chromosome in human (band q24) and mouse (bands D-F4). In the mammalian nervous system, serotonin (5-hydroxytryptamine) binds to distinct cell surface receptor subtypes that are defined by their ligand binding and effector-coupling properties. The 5HT1c receptor is a G-protein coupled receptor that stimulates phospholipase C-catalyzed hydrolysis of phosphatidylinositol bisphosphate, leading to the mobilization of intracellular calcium and to the activation of protein kinase C. By using somatic cell hybrid analysis and FISH, we have mapped the HTR1C locus to the human X chromosome, band q24 and to the mouse X chromosome region D-F4. Comparison of these map positions offers new insights into the evolution of human and murine X chromosomes. Since HTR1C is expressed in certain parts of the central nervous system and abnormal function of the serotoninergic system has been implicated in affective disorders, obsessive-compulsive disorder and epilepsy, establishing the precise map position of HTR1C is an important first step toward evaluating this locus as a candidate for mutations in these syndromes and in X-linked mental disorders.


Structure and expression of the human pseudoautosomal gene XE7. The human pseudoautosomal region comprises a 2.6 megabase segment of the distal short arms of the X and Y chromosomes. Complete DNA sequence homology between the two sex chromosomes is found in this region, and is believed to be important in mediating X-Y pairing in male meiosis. The only known functional genes in this region are MIC2 and CSF2R; in addition a pseudoautosomal location has been proposed for a genetic locus controlling stature. Here we report the structure of a recently identified pseudoautosomal gene, XE7, and its expression in human tissues. Analysis of genomic and cDNA clones shows that alternative RNA splicing results in the production of two predicted protein isoforms, one containing 385 amino acids and the other with 695 residues. The smaller polypeptide is a truncated version of the larger, and results from the inclusion of a cassette exon that introduces an in-frame stop codon into the mRNA. The XE7 gene appears to be ubiquitously expressed, and the production of both protein isoforms is predicted in each of several tissues examined.


Cloning and characterization of an interstitial deletion at chromosome 11p15 in a sporadic breast cancer. In a number of types of cancer including breast, hepatocellular, and bladder carcinoma, frequent losses of heterozygosity (LOH) on chromosome 11p15 have indicated the presence of one or more tumor suppressor genes in this region. In the present study, we report the detection and characterization of a rearrangement at 11p15 in a sporadic breast carcinoma. Genomic DNA clones encompassing the rearranged region were isolated; localization of both flanking clones to 11p15 by two-color fluorescent in situ hybridization (FISH) indicated that the rearrangement was caused by an interstitial deletion in the affected allele. Although it is uncertain whether the region between the flanking two loci was missing from tumor cells, our result implied that a putative tumor suppressor gene on chromosome 11p15 is located between the loci on either side of the interstitial deletion or may be interrupted by one of the breakpoints.


Analysis of mutations at the neurofibromatosis 1 (NF1) locus. A panel of 200 unrelated NF1 individuals has been screened for mutations using a panel of specific clones for the entire gene. DNA analysis on conventional Southern blots indicated that (20) 10% of NF1 patients showed aberrant bands. Small lesions involving nucleotide alterations were detected in a further 10 patients; 5 of these alterations have been fully characterised and are the novel mutations in the NF1 gene. A number of mutations were identified in exon 2. Identical mutations in this exon in two unrelated individuals involved an insertion of cytosine into codon 5662 and resulted in an inappropriate stop codon. This mutation also created a new MnlI site. Another novel mutation in exon 2 resulted from the insertion of thymidine at nucleotide 5678, which also created an inappropriate stop codon. We have so far completed the screen of exons 1-9 of the NF1 gene for the identification of mutations and have found no evidence of clustering of such mutations in the gene.


Microdissection of a human marker chromosome reveals its origin and a new family of centromeric repetitive DNA. A series of procedures including chromosome microdissection, sequence-independent PCR, Southern-blot-hybrid-selection-cloning and sequencing of microdissected DNA-library members were used to analyze DNA from a familial marker chromosome centromere and to determine the origin of the marker chromosome in the case of a live-born, tetraploid human infant. A new family of repetitive DNA, termed sn5 satellite, was sequenced and characterized by DNA hybridization. The sn5 satellite family appears to be primate-specific and shows a chromosome-specific distribution which parallels that of alpha satellite suprachromosomal family 2. This suprachromosomal classification is based on sequence similarity of centromeric alpha satellite DNA within particular groups of chromosomes. It has been postulated that the similarity of alphoid sequences within each of the three suprachromosomal families results from homologous exchanges between nonhomologous chromosomes within each family. The parallel distribution of sn5 satellite sequences at the centromeres of chromosomes of alphoid suprachromosomal family 2 suggests that homologous exchanges between non-homologous chromosomes may be the basis of simultaneous chromosome-specific sequence conservation for multiple centromeric satellite DNA families.


Lambda CM8, a human sequence with putative centromeric function, does not map to the centromere but is present in one to two copies at 9qter. A DNA fragment isolated from a human genomic library, was reported to be present at all human centromeres and present at 16-32 copies per genome. Reintroduction of this DNA into mammalian cells as a concatenated phage clone gave rise to dicentric chromosomes which gave rise to a new, stable, chromosome. Taken together these observations could mean that this DNA is part of a native centromere. We have reexamined the location and copy number of this sequence and find it to be present at 1-2 copies per genome with a single site of in situ hybridisation at 9qter.


A new Tay-Sachs disease B1 allele in exon 7 in two compound heterozygotes each with a second novel mutation. Three novel Tay--Sachs Disease (TSD) mutations have been identified in two unrelated, non-Jewish compound heterozygous patients. A G772C transversion mutation causing an Asp258His substitution is shared by both patients. The mutant enzyme had been characterized, on the basis of previous kinetic studies (1) as a B1, or alpha-subunit active site mutation. This is the first B1 mutation not found in codon 178 (exon 5). A C508T transition causing an Arg170Trp substitution also occurred in one of the patients. The third mutation is a two base deletion occurring in exon 8 involving the loss of either nts 927-928 or 929-930 in codon 310. The deletion creates an inframe termination codon 35 bases downstream. The Arg170Trp mutation was also detected in a third unrelated TSD patient. In both families this allele was traced to French Canadian ancestors originating in the Estrie region of the province of Quebec. This mutation is the third TSD allele unique to the French Canadian population and the ancestral origins of the carrier parents are distant from the center of diffusion of the more common 7.6 kb deletion mutation which is in the eastern part of the province.


A Brassica napus transcript encoding a protein related to the Künitz protease inhibitor family accumulates upon water stress in leaves, not in seeds. A cDNA clone encoding a Brassica napus drought-induced 22 kDa (BnD22) protein has been isolated and characterized. The BnD22 transcript accumulated in response to drought reversibly, and to other conditions of leaf water deficit such as rapid water stress or salt acclimation, but not to cold acclimation or heat shock. Exogenously applied abscisic acid induced both changes in leaf morphology similar to the drought-adaptive response and a pronounced accumulation of the BnD22 mRNA. In control and drought-adapted plants, the BnD22 transcript was expressed in an organ-specific manner: the mRNA level was highest in leaves, low in hypocotyls and undetectable in roots. Sequence analysis indicates that the BnD22 protein is related to the Künitz family of protease inhibitors. In contrast to most members of this family, and also to most polypeptides expressed in vegetative tissues upon drought, the BnD22 mRNA was absent in seeds, before or during the seed desiccation phase. The BnD22 gene represents a new class of genes which are strictly induced in vegetative tissues upon environmental stress, and its pattern of expression shows that the responses to water deficit differ, at least partially, in seeds and in leaves.


Characterization of a pollen-specific cDNA from sunflower encoding a zinc finger protein. We have isolated, via differential hybridization screening of a floral cDNA library from sunflower, a cDNA clone that hybridizes to a 1100 nucleotide-long mRNA found exclusively in mature pollen grains. The cDNA encodes a 219 amino acid-long polypeptide containing two potential zinc fingers alternating with two basic domains. A similar organization is found in the erythroid-specific transcription factor Eryf1 from chicken and its murine homolog GF-1. The C-terminus of the protein contains a sixfold repeat of the pentapeptide sequence (S,T,A)(E,D)TQN. These features suggest that the SF3 protein is a transcription factor required for the expression of late pollen genes. The SF3 gene is a member of a multicopy gene family. A genomic copy of the gene has been isolated and sequenced; it is split by four short, AT-rich introns.


The ptl1 gene expressed in the transmitting tissue of Antirrhinum encodes an extensin-like protein. ptl1, a gene expressed specifically in pistil transmitting tissue of Antirrhinum flowers, encodes a protein with similarity to plant extensins. The protein is rich in proline (28%) and serine (9%) and contains several proline-rich repetitive amino acid motifs found in other extensin-like proteins. The presence of three consensus N-glycosylation sites indicates that it is probably glycosylated. RNA blots show that the ptl1 transcript is abundant in mature pistillar tissue but absent from immature flower buds and all other plant organs tested. In-situ localization of mRNA demonstrates that ptl1 expression is confined to the transmitting tissue of the style and stigma. The presence of a putative signal peptide at the N-terminus of the protein, taken together with the expression pattern, indicates that the ptl1 product may be secreted into the extracellular matrix of the transmitting tissue. The possible contributions of the ptl1 product to the physical properties of the transmitting tissue are considered in the light of current views on extensin structure and function.


The adenine nucleotide translocator of higher plants is synthesized as a large precursor that is processed upon import into mitochondria. Two maize genes and cDNAs encoding the mitochondrial adenine nucleotide translocator (ANT), a nuclear-encoded inner mitochondrial membrane carrier protein, have previously been isolated in this laboratory. Sequence analysis revealed the existence of much longer open reading frames than the corresponding fungal and mammalian ANT genes. Potato ANT cDNAs have subsequently been isolated and sequenced and alignment of the deduced plant amino acid sequences with the equivalent fungal and mammalian polypeptides indicated that the plant proteins contain N-terminal extensions. When the plant cDNA clones are expressed in vitro they direct the synthesis of precursor proteins that are specifically processed at the N-terminus upon import into isolated mitochondria. N-terminal amino acid sequence data obtained from the native proteins purified from both maize and potato mitochondria has allowed identification of the putative processing sites. Further import analysis has shown that two distinct regions of the maize precursor protein contain targeting information, the 97 amino acids at the N-terminus and the 267 C-terminal amino acids. This is the first report that provides experimental evidence that the adenine nucleotide translocator of higher plants is synthesized as a large precursor protein that is specifically cleaved upon import into mitochondria. Import of ANT into higher plant mitochondria therefore appears to be different to the corresponding process in fungal and mammalian systems where targeting of ANT to mitochondria is mediated by internal signals and there is no N-terminal processing.


Molecular analyses of a barley multigene family homologous to the yeast protein kinase gene SNF1. Genomic sequences homologous to the yeast gene SNF1 have been isolated from barley (Hordeum vulgare) cv. Sunbar. SNF1 encodes a protein serine/threonine kinase required for the derepression of a number of genes, including SUC2 (invertase) in response to glucose deprivation. Southern blotting showed the presence of a family of related genes in barley and full-length sequences have been determined for two members of the family, one of which lacks an exon and is almost certainly non-functional. A partial sequence has been obtained for a third member of the family. The transcription start site of one of the genes has been determined by S1 nuclease protection. A transcript almost identical in sequence to the exons of one of the genes has been amplified from barley endosperm mRNA using the polymerase chain reaction. One of the full-length genomic sequences contains nine introns and 10 exons and the number and position of the introns in the second full-length sequence is identical except that it lacks exon 2. However, the length and sequence of the introns vary. Northern blot analyses indicated that related transcripts are present in aleurones, coleoptiles, endosperms, internodes, leaves, ovules, roots and root tips, with highest levels of expression in the aleurones and endosperms.


Efficient initiation of translation at non-AUG triplets in plant cells. The efficiency of translation initiation at triplets differing at one residue from AUG was tested by transient expression in protoplasts from two different plant species. All possible alternative codons were tested. Some triplets showed significant CAT activity, with CUG (30% of the AUG activity) being most active. Most others had between 5 and 15% of the activity obtained from AUG, whereas UUG and AUC yielded about 2% and the two composed only of purines, AAG and AGG, had no significant activity. Translation initiation from AUC, especially, responded to leader sequences outside the immediate context which did not affect translation initiation from AUG.


A pathogen-induced gene of barley encodes a protein showing high similarity to a protein kinase regulator. A full length cDNA of a barley leaf messenger, found to increase in amount during infection attempts by the powdery mildew fungus (Erysiphe graminis), is characterized. The messenger encodes a polypeptide of 261 amino acid residues with a calculated mass of 29.2 kDa and a pI of 4.6. Sequence comparisons as well as serological studies demonstrate that the encoded protein is closely related to a family of mammalian proteins believed to have functions associated with the multifunctional Ca(2+)-dependent protein kinases.


The promoter of the rice gene GOS2 is active in various different monocot tissues and binds rice nuclear factor ASF-1. A single copy gene has been isolated, termed GOS2, from rice. Sequence comparison revealed highly similar genes in mammals and yeast, indicating that GOS2 encodes an evolutionary conserved protein. GOS2 mRNA was detected in all tissues examined. When the upstream region was translationally fused to the reporter gene gusA it was found to drive expression in a variety of rice tissues and in cell suspensions of other monocot species following introduction by particle bombardment. Therefore, the GOS2 promoter is potentially useful for genetic engineering of monocots. A DNA-binding activity from rice, termed rice ASF-1, with similar binding specificity as the cloned tobacco transcription factor TGA-1a, was found to bind to a TGACG sequence motif in the GOS2 promoter. Possible roles for rice ASF-1 in the transcriptional activation of the GOS2 promoter are discussed.


Molecular characterization of cDNA encoding for adenylate kinase of rice (Oryza sativa L.). Two types of genes (Adk-a, and Adk-b) encoding for adenylate kinase (AK, EC 2.7.4.3.) were isolated from the cDNA library constructed from poly(A)+ RNA of rice (Oryza sativa L.). Two cDNAs were heterogeneous at 5' and 3' ends of non-coding sequences and had possible polyadenylation signals. One of the genes, Adk-a, had 1154 bp sequences encoding 241 amino acid residues, while the other type, Adk-b, contained 1085 bp sequences encoding for 243 amino acid residues. Homology between Adk-a and Adk-b was 73.7% in nucleotide sequences, and 90.8% in amino acid level. Two genes showed about 53% homology to bovine mitochondrial adenylate kinase (AK2) at nucleotide and amino acid levels. Concerning the codon usage of rice AK genes, T was abundant at the third position of a codon in the reading frames. In order to examine the enzyme activity of the protein encoded by the rice cDNA, Adk-a was cloned into an expression vector, pUC119, which was introduced into Escherichia coli strain CV2, a temperature-sensitive mutant of adenylate kinase. We found that the transformant carrying the rice Adk-a gene in the sense orientation recovered cell growth at non-permissive high temperature (42 degrees C) and expressed enzyme activities higher than the untransformed CV2 and the transformant possessing Adk-a cDNA in the antisense orientation. These observations suggest that rice Adk-a codes a biologically active enzyme. Furthermore, sucrose was found to regulate the transcription of AK genes in rice cell cultures. Organ related accumulation of mRNA in whole plants was also found.


Expression pattern of a tobacco lipid transfer protein gene within the shoot apex. A genomic clone coding for a putative lipid transfer protein was isolated from Nicotiana tabacum. The gene is expressed in all aerial organs of the tobacco plant, with expression being highest in the upper part of the plant and declining towards the base (i.e. with increasing age). In the shoot apex transcript levels are highest in the LI layer, lower in the underlying cell layers, and are again higher in the submeristem region. This pattern is markedly different from those previously described for genes expressed within the shoot apex.


Genome reorganization in Nicotiana asymmetric somatic hybrids analysed by in situ hybridization. In situ hybridization was used to examine genome reorganization in asymmetric somatic hybrids between Nicotiana plumbaginifolia and Nicotiana sylvestris obtained by fusion of gamma-irradiated protoplasts from one of the parents (donor) with non-irradiated protoplasts from the other (recipient). Probing with biotinylated total genomic DNA from either the donor or the recipient species unequivocally identified genetic material from both parents in 31 regenerant plants, each originating from a different nuclear hybrid colony. This method, termed genomic in situ hybridization (GISH), allowed intergenomic translocations containing chromosome segments from both species to be recognized in four regenerants. A probe homologous to the consensus sequence of the Arabidopsis thaliana telomeric repeat (5'-TTTAGGG-3')n, identified telomeres on all chromosomes, including 'mini-chromosomes' originating from the irradiated donor genome. Genomic in situ hybridization to plant chromosomes provides a rapid and reliable means of screening for recombinant genotypes in asymmetric somatic hybrids. Used in combination with other DNA probes, it also contributes to a greater understanding of the events responsible for genomic recovery and restabilization following genetic manipulation in vitro.


A functional promoter shift of a chloroplast gene: a transcriptional fusion between a novel psbA gene copy and the trnK (UUU) gene in Pinus contorta. A comparative transcription analysis of the chloroplast trnK-psbA-trnH region of the two pine species Pinus contorta and Pinus sylvestris is reported. The chloroplast genome of P. contorta has previously been shown to contain a duplicated psbA gene copy integrated closely upstream of the split trnK gene. This rearrangement has resulted in the gene order psbAI-trnK-psbAII-trnH, where psbAII is the ancestral psbA gene copy. In P. sylvestris, a species which lacks the psbA duplication, transcription of the trnK gene originates from a position 291 bp upstream of the trnK 5' exon, adjacent to a canonical promoter structure. In P. contorta, the corresponding promoter structure has been separated from the trnK gene by the insertion of psbAI, and has, in addition, been partially deleted. Analysis of the transcriptional organization of the trnK-psbA-trnH region of the two pine species revealed that the trnK gene in P. contorta is transcriptionally fused to the inserted psbAI gene copy. As a result, trnK is under the control of the psbA promoter in this species and has therefore acquired psbA-like expression characteristics. In P. sylvestris, accumulation of trnK transcripts is not significantly higher in light-grown than in dark-grown seedlings. In contrast, the level of trnK transcripts in P. contorta is approximately 12-fold higher in the light than in the dark. When light-grown seedlings of the two pine species were compared, an approximately 20-fold higher level of trnK RNAs was found in P. contorta. In both pine species, evidence was obtained for trnK-psbA and psbA-trnH co-transcription.


Temporal and spatial expression of a thiolprotease gene during pea ovary senescence, and its regulation by gibberellin. Clones encoding a thiolprotease (tpp) have been isolated from a cDNA library of unpollinated, senescent pea ovaries and its pattern of expression during both ovary senescence and parthenocarpic development have been studied. The sequence of the tpp cDNA displays a high similarity with other plant and animal thiolproteases of the papain group. The homology is highest around the Cys-His of the active centre; a 109 amino acid sequence at the carboxy terminus was found to be homologous only to thiolproteases of plant origin; this part of the mRNA is also present in another pea mRNA that exhibits similar patterns of induction. tpp mRNA shows a temporal pattern of accumulation that precedes that observed for proteolytic activity. Such accumulation did not occur when ovaries were induced to grow parthenocarpically by gibberellic acid (GA) treatment; furthermore the initial low level of expression present in ovaries decreased after GA treatment, indicating that the gene is down-regulated by gibberellins. Spatially, tpp mRNA is localized mainly within the ovule and ovary vascular elements, and transiently within the endocarp of senescent ovaries. This pattern of expression precedes the development of the cytopathogenic effects observed as unpollinated ovaries undergo senescence.


Four distinct nuclear proteins recognize in vitro the proximal promoter of the bean seed storage protein beta-phaseolin gene conferring spatial and temporal control. A proximal promoter (-422/-13) of the bean seed storage protein beta-phaseolin gene contains cis-regulatory elements conferring spatial and temporal gene regulation. To correlate trans-acting elements with these cis-elements, we performed gel mobility shift and exonuclease III protection assays using bean seed nuclear proteins, and identified target sequences of four DNA-binding proteins associated with this promoter. Three CANNTG motifs, CACGTG (-248/-243), CACCTG (-163/-158), and CATATG (-100/-95), were determined as target sequences of the same DNA-binding protein designated CAN. Competition assays using oligonucleotides containing the wild-type or mutated CANNTG motif indicated that the CANNTG motif appears to be a preferred target sequence for CAN binding. Competition assays also demonstrated that DNA-binding protein AG-1 binds to AAAAAG(A/G)CAA (-356/-347, -191/-182), CA-1 binds to two CA-rich sequences (-201/-192, -175/-160), and that a TATA-box binding protein binds to either TATATAA (-43/-37) or TATAAA (-32/-27) or both. Based on these and other results, it is proposed that CACGTG motif (-248/-243) is a major cis-acting regulatory element conferring spatial and temporal control of the beta-phaseolin gene.


A gibberellin-regulated gene from wheat with sequence homology to cathepsin B of mammalian cells. A previous report described several cDNAs corresponding to mRNAs which accumulated in wheat aleurone layers treated with gibberellic acid (GA) (Baulcombe and Buffard, 1983). The protein sequence deduced from one of these clones (2529) has extensive similarity to the thiol protease, cathepsin B from mammalian cells. Southern analysis of wheat DNA has shown that the 2529 mRNA is encoded by a small family of genes carried on the group 4 chromosome. The nucleotide sequence of a member of the gene family expressed at a low level in aleurone layers and the use of a primer extension assay to identify a clone of a member of the gene family producing an abundant mRNA are reported. The 2529 mRNA accumulates in the scutellum and the aleurone layer of germinating grains where its expression is regulated by GA. In the scutellum the expression was restricted to the parenchyma, suggesting that the 2529 product may have a role other than for mobilization of the endosperm.


The root-knot nematode resistance gene (Mi) in tomato: construction of a molecular linkage map and identification of dominant cDNA markers in resistant genotypes. A dominant allele at the Mi locus on chromosome 6 of tomato (Lycopersicon esculentum Mill) confers resistance to three species of root-knot nematodes (Meloidogyne). The resistance, which is associated with a localized necrotic response, was originally introduced into tomato from the wild species Lycopersicon peruvianum. As a step towards the molecular cloning of Mi, we have identified closely linked DNA markers from both cDNA and genomic DNA libraries as restriction fragment length polymorphisms (RFLPs). DNA from tomato populations segregating for nematode resistance was analyzed to generate a high-resolution genetic map of this region. Additional information on gene order was obtained by comparing the size of the introgressed L. peruvianum chromosomal segment within a collection of nematode-resistant tomato lines. Among the four cDNA markers that are tightly linked to Mi, three are dominant, i.e. L. peruvianum-specific. One cDNA marker corresponds to a gene family comprising 20-30 members, one of which is diagnostic for all nematode-resistant genotypes tested. The presence of non-homologous sequences around the Mi gene may contribute to the suppression of recombination in this region of the genome in crosses heterozygous for Mi. The potential of 'walking' from closely linked markers to Mi is discussed.


Identification of an S-locus glycoprotein allele introgressed from B. napus ssp. rapifera to B. napus ssp. oleifera. Self-incompatible Brassica napus ssp. oleifera lines were generated by introgressing the S-locus from the self-incompatible B. napus ssp. rapifera Z line into the self-compatible cultivars, Topas and Regent, resulting in T2 and R2, respectively. Screening of a cDNA library made from R2 stigma RNA produced several candidate SLG (S-locus glycoprotein) cDNAs. One of the cDNAs, A14, was found to be represented in only the R2, T2 and Z lines. In addition, the corresponding A14 gene was demonstrated to segregate with the T2 self-incompatibility phenotype in an F2 population derived from a cross between T2 and Topas, and to exhibit high mRNA levels in the stigmas prior to anthesis. Sequence analysis of the A14 cDNA revealed close homology to B. oleracea SLG alleles associated with a Class I high activity self-incompatibility phenotype.


RNA binding characteristics of a 16 kDa glycine-rich protein from maize. We have previously described a developmentally regulated mRNA in maize that accumulates in mature embryos and is involved in a variety of stress responses in the plant. The sequence of the encoded 16 kDa protein (MA16) predicts that it is an RNA-binding protein, since it possesses a ribonucleoprotein consensus sequence-type RNA-binding domain (CS-RBD). To assess the predicted RNA binding property of the protein and as a starting point to characterize its function we have used ribohomopolymer-binding assays. Here we show that the MA16-encoded protein binds preferentially to uridine- and guanosine-rich RNAs. In light of these results a likely role for this protein in RNA metabolism during late embryogenesis and in the stress response is discussed.


Strength and bite, Part 2: Testing isometric strength using a MORA set to a functional criterion. The effect on isometric strength of biting on three intraoral devices and habitual occlusion was analyzed. Only subjects who showed a relative weakness to the Isometric Deltoid Press (IDP) when biting as opposed to maintaining the mandible in an unsupported rest position were included in the study. Both in the original 35 subjects and the 23 subjects returning on the second day, performance wearing the appliance set by a functional criterion of peak strength (locking) to the IDP was significantly greater than wearing a placebo appliance and a bite raising appliance that deflected the mandible 1 mm to the left. Strength biting on the appliance set by a functional criterion was significantly greater than all these conditions. Strength biting in habitual trials that were matched with the deflection condition was found to be significantly greater than that biting in the placebo condition. It was concluded that a relationship does exist between bite and isometric strength. Previous speculation about the role of placebo effect was not substantiated by the data gathered in this experiment.


Influence of mucosal mechanoreceptors on anterior temporalis EMG activity in patients with craniomandibular dysfunction: a preliminary study. An analysis of saliva swallowing and tonic electromyographic (EMG) activity was undertaken in 15 young adult patients with craniomandibular dysfunction with and without a palatal base inserted. Recordings were performed by placing surface electrodes on the right and left anterior temporal muscles. Saliva swallowing and tonic activity were initially recorded with and without the palatal base inserted. After one week of continuous use of the palatal base, EMG activity was recorded again. Nonsignificant differences in EMG activity were observed in the studied conditions. EMG results do not support the therapeutical use of palatal base as a conservative and reversible treatment in patients with craniomandibular dysfunction.


Evaluation of pressure pain threshold in head and neck muscles by electronic algometer: intrarater and interrater reliability. Using a new electronic algometer, the mean values and standard deviations of pressure pain threshold and the intrarater and interrater reliability were evaluated on 13 muscles of the human head and neck region. The subjects were 40 healthy individuals, 21 females and 19 males. A comparison with data obtained from contralateral muscles failed to demonstrate significant differences. Statistically significant correlation coefficients were obtained from the values of intra-examiners and inter-examiners in all muscles except the medial pterygoid and middle sternocleidomastoid muscle in male subjects (p < 0.05). This study showed that the electronic algometer could be recommended for evaluation of the pressure pain threshold of human head and neck muscles in clinical and experimental studies.


Temporomandibular joint vibration analysis in a sample of non-patients. In a sample of 20 non-patients, 60% of the subjects had an absence of subjective temporomandibular joint (TMJ) complaints (noises/sounds) that agreed with objective joint vibration analyses (electrovibratography). Among the remaining 40% of subjects, only 50% of the examined joints showed agreement between subjective and objective findings. Subjects appeared to be unable to reliably detect "weak" (early) symptoms of TMJ dysfunction but were able to reliably detect "strong" (late) symptoms of TMJ dysfunction and possibly disease. As measured through active protrusion and laterotrusion of the mandible, the guidance angles of the anterior teeth could not explain the absence and presence of TMJ vibrations.


Video display terminal operation: a potential risk in the etiology and maintenance of temporomandibular disorders. Surveys indicate over 50 million Americans, mostly women, currently operate video display terminals (VDTs) at home or in the workplace. Recent epidemiological studies reveal more than 75% of approximately 30 million American temporomandibular disorder (TMD) sufferers are women. What does the VDT and TMD have in common besides an affinity for the female gender? TMD is associated with numerous risk factors that commonly initiate sympathetic nervous system and stress hormone response mechanisms resulting in muscle spasms, trigger point formation, and pain in the head and neck. Likewise VDT operation may be linked to three additional sympathetic nervous system irritants including: (1) electrostatic ambient air negative ion depletion, (2) electromagnetic radiation, and (3) eyestrain and postural stress associated with poor work habits and improper work station design. Additional research considering the roles these three factors may play in the etiology of TMD and other myofascial pain problems is indicated. Furthermore, dentists are advised to educate patients as to these possible risks, encourage preventive behaviors on the part of employers and employees, and recommend workplace health, safety, and ergonomic upgrades when indicated.


Temporomandibular joint adaptation following inferior repositioning of the maxilla in adult monkeys. Treatment of adults with vertical maxillary deficiency (short faces) has continually been an intriguing challenge for surgeons and orthodontists. For this category of patients, the introduction of simultaneous bone grafting and Le Fort I osteotomy has opened the door for improved treatment. However, despite the improved surgical techniques, surgeons have been reluctant to increase the vertical dimension of the maxilla by Le Fort I osteotomy with interpositional bone grafts because of inconsistent and variable stability after surgery. This study examines structural and functional adaptation of the adult temporomandibular joint and stability in a primate model following surgical lengthening of the maxilla in the vertical dimension. Results suggest that maxillary surgery and autorotation can alter condylar stress within physiologic ranges. However, further studies are indicated to clarify the surgery's long-term effect.


Rheumatoid arthritis and its implications in temporomandibular disorders. Rheumatoid arthritis is known to afflict the temporomandibular joint (TMJ) with common symptoms including pain during function, tenderness on palpation, stiffness, and crepitus. New evidence suggests that metalloproteinases may be responsible for tissue changes that occur in rheumatoid arthritis. These enzymes are collagenase, gelatinase, and proteoglycanase. Antiinflammatory drugs are the first line of management for pain and inflammation in rheumatoid arthritis. This paper, however, suggests that because increased joint load is believed to cause a greater expression of destructive metalloproteinase, it is appropriate to assess even the asymptomatic temporomandibular joint and the muscles of mastication for early objective signs of dysfunction or discomfort. Interceptive management, by the use of load-reducing appliance therapy, may enable reduction of the expression of destructive metalloproteinase within the joint, thereby reducing joint destruction.


Comparison of MMPI scores with self-report of sleep disturbance and bruxism in the facial pain population. Sleep disturbance and bruxism are common clinical characteristics of the chronic facial pain patient. Previous studies have shown that chronic pain patients reporting disturbed sleep show more psychopathology and respond less readily to treatment. Bruxism has been linked to emotional stress and periods of difficult life change. The present study explored the question of whether sleep disturbance or bruxism are useful predictors of psychopathology in the facial pain population. Psychopathology was measured by using the Minnesota Multiphasic Personality Inventory (MMPI). It was predicted that facial pain patients who reported sleep disturbance or bruxism would correlate with more elevated scores on the MMPI profiles. The results of the study revealed a strong association between self-report of disturbed sleep and higher MMPI scores. No difference between the MMPI scores of bruxers and non-bruxers was found. It was concluded that sleep disturbance may be an effective predictor of psychological disturbance within the facial pain population, while bruxism was not found to be associated with psychological disturbance as measured by the MMPI.


Changes in elongation of falx cerebri during craniosacral therapy techniques applied on the skull of an embalmed cadaver. Craniosacral therapy supports that light forces applied to the skull may be transmitted to the dura membrane having a therapeutic effect to the cranial system. This study examines the changes in elongation of falx cerebri during the application of some of the craniosacral therapy techniques to the skull of an embalmed cadaver. The study demonstrates that the relative elongation of the falx cerebri changes as follows: for the frontal lift, 1.44 mm; for the parietal lift, 1.08 mm; for the sphenobasilar compression, -0.33 mm; for the sphenobasilar decompression, 0.28 mm; and for the ear pull, inconclusive results. The present study offers validation for the scientific basis of craniosacral therapy and the contention for cranial suture mobility.


Reading the medical record. I. Analysis of physicians' ways of reading the medical record. Physicians were interviewed about their routines in everyday use of the medical record. From the interviews, we conclude that the medical record is a well functioning working instrument for the experienced physician. Using the medical record as a basis for decision making involves interpretation of format, layout and other textural features of the type-written data. Interpretation of these features provides effective guidance in the process of searching, reading and assessing the relevance of different items of information in the record. It seems that this is a skill which is an integrated part of diagnostic expertise. This skill plays an important role in decision making based on the large amount of information about a patient, which is exhibited to the reader in the medical record. This finding has implications for the design of user interfaces for reading computerized medical records.


A scanning system for digital analysis of cineangiography films. A system for scanning and digital analysis of cinefilms is presented and its performance is compared with entirely digital radiographic equipment. Apart from the difference between logarithmic and linear gray-scale representation, a higher noise level was found in the scanning system. When its spatial resolution was assessed visually, it was comparable to that of the digital system, although lower than when the cinefilming and scanning steps were evaluated separately. Algorithms for the correction of varying exposure and geometric ("pin-cushion") distortion are also presented. It is concluded that digital analysis after scanning of cinefilms can be a useful alternative to completely digital cineradiographic studies.


Reading the medical record. II. Design of a human-computer interface for basic reading of computerized medical records. A user interface for reading the medical record was designed and implemented on a workstation with a 19-inch colour screen. The text is presented on imitations of paper-pages. The pages are organized in bundles which are dynamically connected to scrollable index lists. The turning of pages on the screen is the fundamental concept of the interface. A page can be turned by a mouse-click or by a circular mouse-movement. Elaborated feedback is given to the user in order to provide effortless orientation and navigation. The interface supports the basic ways of use identified in our analyses of reading habits. It also enables human perceptual and cognitive skills to be used. It seems very easy to learn and efficient in use.


PRIST-2: a Graphic User Interface based tool for the development of medical software. A 4th generation tool, called PRIST-2, is presented that has been designed as an interactive environment for the rapid prototyping of clinical applications in a large-scale Hospital Information System project. We adopted an SQL-based commercial Relational Data Base Management Systems (RDBMS) to guarantee portability on different hardware and operating systems. Relational databases, however, are characterized by a simple data structure and do not incorporate the application semantics required to ensure a high degree of data independence. To reach this goal, we propose an extension to the relational model, adding some of the main characteristics of the Object Oriented Data Base Management Systems (OODBMS) approach, such as "types" and "encapsulation".


A computerized analysis system for vigilance studies. A digital signal analysis system for vigilance studies is presented. The analysis is based on adaptive segmentation, band pass filtering, nonlinear eye movement detection and rule-based decision making. A preliminary evaluation of seven subjects falling asleep showed that the system is able to detect small vigilance fluctuations reliably.


A low-cost system for digital image processing of moving images in real time: application to X-ray fluoroscopy. A low-cost image processing system and two real-time digital image processing algorithms using parallel processing have been developed to provide automatic equalization of moving images at video frequencies. The algorithms differ in the processing time required and the characteristics of the final image. The system takes an entire image from the video sequence, digitizes it, automatically calculates its histogram and the lowest and highest useful grey levels, equalizes the histogram, and finally converts it to the analogue image. Methods were applied to X-ray fluoroscopy (angiography) images, which are usually saturated or of uniform intensity (low contrast), leading to information loss. An application of these methods is in interventional radiography, which requires images in real time.


Periodontal healing of replanted dog teeth stored in Viaspan, milk and Hank's balanced salt solution. This study examined, histologically, periodontal healing and root resorption of replanted dogs teeth stored in Viaspan for different time periods and compared these healing patterns to those after storage in milk or Hank's balanced salt solution (HBSS). Seventy-two beagle incisors were endodontically treated, extracted, randomly divided and placed in Viaspan or milk for 6, 12, 24 and 36 h, and Viaspan or HBSS for 36, 48, 72 and 96 h, after which they were replanted. Four negative control teeth were immediately replanted while four positive controls were allowed to dry for one hour before replantation. All replanted teeth were splinted for 14 days. Two months after replantation the dogs were killed and the teeth histologically examined for healing of the supporting tissues. For Viaspan neither replacement nor inflammatory root resorption was seen after 6 and 12 h storage. A statistically significant rise in the incidence of replacement resorption was seen at 24, 36 and 48 h which decreased again at 72 and 96 h to levels equal to storage for 6 and 12 h. The occurrence of inflammatory root resorption was low and significantly increased only at 48 h after which it decreased significantly again. Viaspan proved superior to milk as a storage medium. Teeth stored in HBSS showed healing results similar to those stored in Viaspan.


The determination of the absolute bioavailability for drug substances with long elimination half-lives (with PC-programs for the method of truncated areas). A survey is given of the methods for the determination of the absolute bioavailability for drug substances with long elimination half-lives. All methods depend on the assumption of linear pharmacokinetics. Emphasis is laid on Urso and Aarons' regression method of truncated areas-under-the-curve (AUC) to obtain estimates of the absolute bioavailability, F, and the absorption rate constant, ka, without obeying the otherwise general rule of following blood or plasma levels for at least three times the terminal half-life. It is shown by simulation when the linear and when the logarithmic trapezoidal rule is to be used for the calculation of the AUC. Two PC-programs for the regression method of truncated areas are presented: one program (SIMF&KA.EXE) simulates, based on tentative pharmacokinetic parameters, whether a blood sampling scheme, together with the precision of the analytical assay, is adequate to obtain accurate and precise estimates of F and ka; the method is insensitive to large variations in the tentative value of the elimination half-life. The other program (ESTF&KA.EXE) provides estimates of F and ka, with standard deviations of the estimates, from empirical data.


Observations of acoustic streaming fields around an oscillating ultrasonic file. The steady acoustic streaming generated around straight and precurved oscillating ultrasonic files driven by the Piezon-Master 400 unit was examined in the free field and in small channels using a stereomicroscope. In addition, the effect of file-wall contact on streaming production was also investigated. The results indicated that the ultrasonic files can generate acoustic streaming both in the free field and in the small channel. Higher velocity streaming was observed when smaller size files were employed and when the file was precurved. Light file-wall contact did not totally inhibit streaming while severe file-wall contact inhibited movement of the file and, as a result, no streaming was observed. The positions and length scales of the streaming vortices appeared to be influenced by the presence of boundaries. In the free field, two rows of vortices were situated along the sides of the file while in the small channel, the vortices were positioned above the surface of the file. These results indicated that it is possible for acoustic streaming to occur in a confined space as in a root canal provided that severe file-wall contact is avoided. It is therefore recommended that light filing or allowing the file to freely vibrate during some stage of treatment should be carried out in order to generate streaming in the root canal.


Computer-assisted rheological evaluation of microsamples of mucus. Dynamic viscoelasticity measurements are required in many studies on biological fluids and they can be performed by determining the corresponding strain when a sinusoidal shear stress is applied to a sample. In several circumstances the amount of fluid that can be obtained for analysis in physiological conditions does not exceed microliters. In this context, the microrheometer technique is a useful approach to determine the dynamic rheological profile of the samples. However, the manual calculation of the desired parameters is tedious and time-consuming. This paper describes a menu-oriented program in order to facilitate its use by non-experts. The comparison between manual and computer-aided calculations demonstrated that the program reduced the time of measurement, and reduced intra- and interobserver variations. The program was developed on an IBM compatible PC in Microsoft C 5.1, and tested in a blind study to check the advantages in terms of time and reproducibility of the system verified by the concordance of two independent observers (interobserver influence) in two different occasions (intraobserver influence).


Using the job-exposure matrix for elaborating job histories. A first software (JHS) for the elaboration of job histories oriented toward risks was designed and results published In an article "A software for the elaboration of Job Histories". This article presents a second software (JES), based on the use of a job-exposure matrix designed for one company. The matrix is essentially a database, an organized gathering of information concerning the company. The two softwares are inter-faced and both run on a PC. When properly exploited, the two softwares can serve as an asset for epidemiological studies dealing with occupational health.


Morphology of the mineralizing front and observations of reparative dentine following induction and inhibition of dentinogenesis in the rat incisor. An extra oral approach was made to 26 pairs of Wistar rat incisors and a small bur used to expose the pulps which were then dressed with either calcium hydroxide paste (Pulpdent) zinc oxide-eugenol cement (Kalzinol) or a triamocinolone acetonide/tetracycline containing cement (Ledermix). Animals were sacrificed at 7 days, incisors removed, a window cut to the pulp opposite the site of exposure, soft tissues removed with 7% NaOCl for 30 minutes before teeth were dehydrated in graded concentrations of acetone and gold coated for examination under SEM. Calcium hydroxide produced rapid complete repair with a remarkably regular formation of calcospherites, except for a zone of relative inhibition perforated by nutrient canals at the periphery of each lesion. Both zinc oxide-eugenol and triamcinolone acetonide cements inhibited both bridging of the defect created by the exposure and dentine formation in the surrounding pulpal wall. Data was grouped according to the degree of hard tissue repair. The results were statistically significant (Chi-square p < or = 0.001). This method demonstrated qualitative and quantitative differences in the repair process resulting from chemical variations in the dressings applied.


Computer processing of artifact and arrhythmias in heart rate variability analysis. Analysis of heart rate variability (HRV) with Holter monitoring is often difficult due to excessive artifacts and arrhythmias. While short sudden surges are treated successfully by most methods, slow heart rate (HR) variations, nocturnal trapezoidally-shaped HR increases and special types of arrhythmias which are similar to normal HRV fluctuations may distort further time domain and spectral analysis. This paper examines the advantages and disadvantages of different methods for preprocessing of HR data. We have developed the following approach to the analysis of HRV. (1) A combination method based on the absolute difference between HR values and both the last normal HR value and an updated mean is used for removal of artifacts and arrhythmias. This method can detect both sudden surges in HR values as well as longer periods of noise combined with slow normal variations. An additional stage of wild point removal is then optionally applied. (2) Certain special problems such as large T-waves, bigeminal rhythm, slow HR variations and nocturnal trapezoidally-shaped HR increases are also identified. Although none of the algorithms can be applied successfully to all cases, the final computer analysis for preprocessing described in the present study has proved to be superior to the simplified methods which are usually used and provides more suitable data for HRV analysis.


Effect of cervical coating of ethyl cellulose polymer and metacrylic acid copolymer on the radicular penetration of hydrogen peroxide during bleaching. Extraradicular leakage of oxidizing agents during bleaching is an undesirable event and thus need to be prevented. The effect of external cervical coating of ethyl cellulose (EC) and metacrylic acid copolymer (MAC) on the radicular penetration of hydrogen peroxide during intracoronal bleaching was examined. Single rooted human premolars extracted for orthodontic reasons were used. The cementum covering the cemento-enamel junction was mechanically removed and the teeth treated endodontically and bleached with 30% hydrogen peroxide. Radicular hydrogen peroxide penetration was measured before coating the teeth and after applications of 1-3 layers of EC or 3 layers of MAC external cervical coatings. It was found that the radicular penetration of 30% hydrogen peroxide was related to the number of layers of cervical EC coatings. Application of one layer of EC did not reduce the hydrogen peroxide penetration. Two and three layers of EC reduced the hydrogen peroxide penetration by 38% and 85% respectively. Three layers of MAC reduced the radicular hydrogen peroxide penetration in 83%. Statistically, a highly significant difference was found between the teeth coated with three layers of either EC or MAC and the noncoated teeth (p < 0.001). It was concluded that application of ethyl cellulose or metacrylic acid copolymer to exposed cervical root surfaces may effectively prevent extraradicular leakage of bleaching agents.


Special computer graphical method for detection of myocardial infarction. The application of computer graphics for detection of myocardial infarction is reviewed and a special method is described. It is based on construction of two isointegral maps (Q wave map and ST segment map) realized in contour representation and using the Selvester distribution of the left ventricle.


A comparison of four root canal obturation methods employing gutta-percha: a computerized analysis of the internal structure. The purpose of the present investigation was to compare the internal structure of gutta-percha for presence/absence of empty spaces when used in four different obturation methods: thermoplastic, chloroform-softened, thermomechanical, and warm lateral condensations. Each obturation was performed five times in a metal mold representing a root canal system. Following obturation the mold was disassembled and the gutta-percha was freeze-fractured at the 1.0, 3.5, and 6.5 mm levels as measured from the tip of the obturations. The fractured gutta-percha was placed in a scanning electron microscope, the image transferred to a computer, and converted to digital data. The results were subjected to statistical evaluation. The results demonstrated no difference between the obturation methods at the 1 mm level, however at the 3.5 mm level, thermomechanical condensation produced an internal structure characterized by a greater number of empty spaces (p < 0.0007). At the 6.5 mm level, thermomechanical condensation differed only from the chloroform-softened gutta-percha (p < 0.01).


GCG Stacks: a friendly interface for the GCG programs. A 'PLUS' stack which provides a friendly user interface for the GCG suite of programs is presented. The interface takes advantage of the whole set of programming tools available in a graphical and object-oriented environment and its major features include: (i) an efficient management of the on-line help documents, and (ii) a flexible editor for macrocommands. The former facilitates finding specific information in the huge documentation bundled with the GCG suite, and the latter is useful whenever several GCG programs must be run in sequence with automatic piping of the intermediate results.


Traumatic injuries to primary teeth in Mexico City children. The purpose of this retrospective study was to analyse traumatic injuries to primary teeth in children attending an emergency dental service in a pediatric hospital in Mexico City. A total of 563 children 6-mo to 7 yrs-old were treated during the period from January 1981 to December 1987. The 563 children presented 936 traumatic dental injuries. The most common type of trauma was soft tissue injury, followed by luxation and avulsion. More males presented with traumatic injuries (61.8%) than females (38.2%). In both sexes, maxillary teeth received more traumatic injuries than mandibular teeth. Children 2-3 yrs old presented the highest number of injuries (195) followed by the 4-5 and 6-7 year-olds. The largest number of injuries were seen during winter (36%) followed by summer (25%), spring (21%) and fall (18%).


Two-dimensional distribution of sound velocity in ground sections of dentin. The longitudinal velocity of sound in a specific material depends, amongst others, on the material's density and elasticity (Young's Modulus). Ultrasound therefore may be used for indirect characterization of materials. In this paper a method is described which allows high resolution measurements on coplanar ground sections of human teeth. The results are presented in two-dimensional velocity profiles. There is evidence from the first images, that longitudinal sound velocity (LSV) in dentin varies depending on the location. The use of LSV may be another way to characterize hard dental tissues physically, and to monitor induced changes.


A case of progressive external root resorption treated with surgical exposure and composite restoration. Progressive external, root resorption was observed apical to the alveolar crest on the buccal surface of a tooth. The area of root resorption was surgically exposed. To gain access to the root resorption cavity osteoectomy was performed. The soft tissue in the resorption cavity was removed and a composite filling (Retroplast) was placed in the cavity using a dentine bonding system (Gluma). The pulp was removed and the root canal was obturated with gutta-percha points and root canal sealer (AH26). Eight months after treatment no further root resorption was observed. Increased pocket depth and slight bleeding on probing in the area of resorption were evident.


Influence of irrigation and intracanal dressing on the healing process of dogs' teeth with apical periodontitis. Dogs' teeth with apical periodontitis were treated endodontically, Dakin's solution being used in an experimental group as the irrigation solution, and camphorated paramonochlorophenol as an intracanal dressing. For a second group of teeth, the irrigation solution used was physiologic saline, dry cotton only being placed into the pulpal chamber to take the place of an intracanal dressing. In a second visit, overinstrumentation and a new application of the same kind of dressing were performed, the root canals being then filled with gutta-percha cones and zinc oxide-eugenol cement. Other specimens were treated, in one visit, where physiologic saline or Dakin's solution were the irrigation solutions. The animals were sacrificed 6 months after the obturation of the root canals. Histologic exams showed better results for the experimental group where Dakin's solution and camphorated paramonochlorophenol had been used, with signs of repair characterized by newly formed cementum and bone tissue, as well as a marked reduction in size of the periapical lesions. No differences were seen in the results with physiologic saline or Dakin's solution as irrigants.


Reasons for and incidence of tooth mortality in a Swedish population. Longitudinal studies on tooth mortality are rare but the reasons for tooth mortality have been studied by several authors. The aims of this investigation were to study the reasons for and incidence of tooth mortality in an earlier described Swedish population of 200 patients on two occasions with an interval of 5-7 years, and to see if the reasons for extractions were correlated to posts, crowns or endodontic status, respectively. 197 (4.0%) of the 4889 teeth registered at the first examination were lost during the interval. 65 (33%) of the lost teeth were endodontically treated. 44 (68%) of these were registered as having one or more root with a root-filling ending more than 2 mm from the apex and 29 (45%) were judged to have an improper seal. In 93 of the 197 lost teeth it was possible to find the reason for extraction from the patient chart. Based on distribution of selected variables, these 93 teeth seemed to be representative of the whole group of 197. It was concluded that tooth losses were evenly distributed in the different age-groups and that above all molars but also premolars were lost more often than teeth in the frontal region. Furthermore, endodontically treated teeth were lost more often than other teeth and the quality of the root-filling affected the risk for losses while crowned teeth did not run a higher risk of being lost than teeth without crowns. Finally, it was found that caries, including pulpitis and apical periodontitis, was the main reason for tooth extractions.


An experimental study of the stability of irradiated teeth in the region of the dentinoenamel junction. In this in vitro study we investigated the influence of ionizing gamma rays on the stability in the region of the dentinoenamel junction. We removed the enamel on the labial surface of 30 incisors of bovines up to the dentinoenamel junction, so that a circular area of enamel with a diameter of 2.0 +/- 0.1 mm was left and an enamel cylinder was created. 15 teeth were irradiated by a cobalt-60-source (energy dose 70 Gy). The other 15 teeth were used as controls. Using a material testing apparatus the shear bond strengths were measured by breaking off the enamel cylinders. Furthermore, the breaking modes were investigated in SEM. Comparing the results of the shear bond strength experiments, it was obvious that the stability in the region of the dentinoenamel junction was significantly less among the irradiated teeth than among the non-irradiated teeth. The median value of the gamma ray treated teeth was x = 19.1 MPa and that of the non-ray-treated teeth was x = 37.4 MPa. The non-irradiated teeth showed fractured surfaces only in dentin in 10 cases and in 5 cases in both dentin and enamel. In contrast to that, the irradiated teeth had fractured surfaces in 12 cases exclusively in dentin and only in 3 cases the enamel was also fractured. These results lead us to conclude that changes of biophysical property of teeth can be caused by the influence of ionizing rays.


Pulpal and radicular changes following maxillary subapical corticotomy. Pulpal and radicular changes after subapical corticotomy in combination with posterior transfer of the maxilla were studied histopathologically using monkey jaws. When the surgical procedures were successful, the pulp tissues were kept alive, even though some slight atrophy and degeneration appeared. In some cases, however, severe reticular atrophy occurred which might be due to anaemia during operations.


Profiling of Propionibacterium acnes recovered from root canal and blood during and after endodontic treatment. This report describes the first results of an ongoing study of bacteremia after endodontic treatment of teeth with Asymptomatic apical periodontitis. After access cavity preparation, microbiological samples were taken from the root canal under aseptic conditions in 4 single-rooted teeth in 4 patients. In treatment of 2 of the patients, the first 3 reamers (sizes 15-25) were deliberately used to a level 2 mm beyond the apical foramen. In 2 patients the instrumentation ended inside the root canal 1 mm short of the apical foramen. Blood samples were taken from the patients during the endodontic instrumentation and 10 min after the treatment was completed. Using lysis-filtration under anaerobic conditions, the blood was passed through a cellulose membrane filter. The filters as well as the root canal samples were incubated using an anaerobic technique. Anaerobic bacteria were isolated from all root canals. In the 2 patients where overinstrumentation had occurred, Propionibacterium acnes was recovered both from the root canals and from the blood samples taken during and after the treatment had been completed. Biochemical profiles, antibiotic susceptibility tests and electrophoresis of soluble proteins revealed that Propionibacterium acnes isolated from the root canal and blood samples were identical within patients, but varied between patients. Facultative anaerobic bacteria including Streptococcus sanguis were recovered from only one root canal sample and not from the blood samples.


Ectopic eruption of a maxillary canine following trauma. Traumatic events at an early age may lead to developmental dental anomalies and ectopic tooth eruption. A case is reported in which a traumatic injury at two months of age resulted in the development of supernumerary teeth in the upper right premaxillary region. The maxillary canine ectopically erupted or transposed into the space left by the missing central incisor and eliminated the need for a prosthesis in this region.


Generalized "complete" calcific degeneration or pulp obliteration. Extensive calcification of the pulp is a pathologic condition that occurs as an answer to various factors (trauma, caries, periodontal disease). The increase in the amount of calcification may lead to partial or complete radiographic, but not microscopic, obliteration of the pulp chamber and root canals. Complete calcific degeneration (pulpal obliteration) may be found in two forms, generalized or localized. The generalized form which is presented in the present case report is probably part of the aging process.


[The efficiency of thermoregulatory reactions in the cooling of the body]. Immersion of the rabbit body model in water of 4 degrees C temperature induced fast cooling of the model even though the heater of the model was 3-fold more powerful than the respective heat-production mechanism in a live rabbit. Only 10-11-fold more powerful heat production was able to keep the model temperature about 37 degrees C.


[The neuronal activity of the ventromedial hypothalamus during pharmacological exposures that modulate motivational and emotional states]. Neuronal activity of the ventromedial hypothalamus was studied in food- and water-deprived, saturated unrestrained rats and after i. p. administrations of alcohol, nembutal, 5-HT and disulphiram. The neurons whose activity did not depend on motivational states decreased their firing rate. The data obtained suggests that motivational and emotional effects of the ventromedial hypothalamus are based on various cell mechanisms.


[Visual recognition processes in monkeys and their neuronal correlates in the visual cortex: the effect of an M-cholinoreceptor blocker]. Unit activity was studied in the visual cortex prior to and after amyzyl administration in monkeys trained for delayed visual differentiation of different colour stimuli. The data obtained suggests that the cholinergic mechanisms of the visual cortex are involved in the visual recognition and seem to play different functional roles at different stages of the behaviour.


[The informational significance of the pulse waves of an intracerebral rheoencephalogram]. The evidence obtained on the pulse waves of intracerebral rheoencephalogram in rabbits and cats, suggests active responses of cortical vessels to the loads altering the correlation of the CSF and blood pulse volumes in the process of formation of these waves. The intracerebral rheoencephalogram seems to be able to reflect the changes of both the vascular tone and the brain tissue hydration.


[The effect of the ambient temperature and motor activity on brain temperature in bullfinches]. In increasing of the ambient temperature, the difference between the brain and body temperatures diminished from 1.4 degrees C (at the ambient temperature 0 degree C) to 0.5 degrees C (at the ambient temperature +37 degrees C) in bullfinches, the brain temperature being always the lower one. In combination of high ambient temperature and locomotor activity the brain-body temperature difference increased as the body temperature had raised higher than the brain one.