The divergent promoters mediating transcription of the par locus of plasmid RP4 are subject to autoregulation.

The partitioning region of broad-host-range plasmid RP4 contains four genes (parA, parB, parC, and parD) that encode products essential for partition activity. Two divergently arranged promoters located in the intercistronic region between parC and parD mediate transcription of these genes. The transcriptional initiation sites for both promoters were determined by primer extension. Transcriptional fusions were used to show that parA, parB, and parC are combined in an operon, while parD constitutes a separate transcription unit. Both parCBA (genes in order of transcription) and parD are negatively autoregulated at the level of transcription by the gene products of parA and parD, respectively. parD promoter mutants which have become insensitive to repression by parD were isolated. Comparison of wild type and the mutant parD promoter sequences indicated that three short repeats are likely involved in the negative regulation of this promoter. Potentially these sequence elements comprise target sites for the ParD protein.


Transcription and autoregulation of the stabilizing functions of broad-host-range plasmid RK2 in Escherichia coli, Agrobacterium tumefaciens and Pseudomonas aeruginosa.

The broad-host-range plasmid RK2 has been shown to encode several proteins important for its maintenance within bacterial populations of a number of Gram-negative bacteria. Their genes are organized into two operons: parCBA and parD. These operons have been proposed to be transcribed from two divergent promoters, p-parCBA and p-parD, located within a sequence of approximately 150 bases. In this report we identify and characterize the sequences required for regulated transcription from these promoters in Escherichia coli, Agrobacterium tumefaciens and Pseudomonas aeruginosa. Both of these promoters are repressed by their own gene products in the same manner in all three bacteria tested, with ParA functioning as the primary repressor of p-parCBA and ParD functioning as the repressor of p-parD. The binding regions of these proteins were determined through deletion analyses, DNA mobility shift assays, and an examination of the effect of mutations in this region. Based on these observations, the ParA protein appears to bind to either two inverted repeat or two direct repeat sequences, one downstream from the transcriptional initiation site and the other upstream of the p-parCBA -35 box. The ParD protein appears to bind to one inverted repeat sequence, located between the -35 and -10 boxes of p-parD.


Negative transcriptional control of iron transport in Erwinia chrysanthemi involves an iron-responsive two-factor system.

Systemic virulence of the phytopathogen Erwinia chrysanthemi 3937 requires a functional iron assimilation system which, in this enterobacterium, is mediated by the siderophore chrysobactin and the outer membrane transport protein Fct. We investigated the regulation of this system by iron. No direct similarity with the Escherichia coli fur gene was found. Insertional mutagenesis allowed isolation of a regulatory mutant which expressed chrysobactin and two other high-affinity iron transport systems previously characterized in strain 3937, regardless of the iron level. RNA/DNA hybridization analysis established that regulation of chrysobactin by iron occurs at the transcriptional level. From a wild-type gene library, a recombinant cosmid able to restore normal regulation in the mutant strain was isolated. By generating a series of subclones and mini-Mulac insertions, we identified a regulatory locus (cbr) extending beyond c. 2.5kb which encodes two polypeptides, CbrA and CbrB, with molecular weights of 34,000 and 55,000 respectively. Functional analysis of the locus suggests that the cognate genes cbrA and cbrB are clustered within an operon. Their expression was studied through chromosomal lac gene fusions, in the presence of plasmid-borne wild-type constructions, under high- and low-iron conditions. In summary, the data show that in the presence of iron, cbr negatively regulates the chrysobactin biosynthetic and transport genes, while under conditions of depletion, cbr is subject to negative autogeneous regulation.


Characterization of a novel regulatory gene governing the expression of a polyketide synthase gene in Streptomyces ambofaciens.

A key step in the biosynthesis of macrolide antibiotics is the assembly of a large macrocyclic lactone ring by a multienzyme protein complex called the polyketide synthase. In the species Streptomyces ambofaciens, the polyketide synthase for the assembly of the 16-membered ring of the macrolide antibiotic spiramycin is encoded by the biosynthetic gene srmG. Here we show that the accumulation of transcripts from the srmG promoter is governed by the regulatory gene srmR, whose predicted product, a 65 kDa polypeptide, is not significantly similar in its deduced amino acid sequence to that of previously reported proteins in the protein databases. The srmR gene product is also required for the accumulation of transcripts from srmX, an additional gene in the vicinity of srmR, but not for the accumulation of transcripts from srmR itself. Interestingly, mutations in srmR prevent the accumulation of transcripts from the spiramycin resistance gene srmB, but this is an indirect consequence of the failure of srmR mutants to produce spiramycin, which is an inducer of its own resistance gene. The possibility that srmR is the prototype for a new class of regulatory genes governing early events in the biosynthesis of macrolide antibiotics is discussed.


The role of syllabic and orthographic properties of letter cues in solving word fragments.

The present research examined the role of phonological and orthographic properties of cues in mediating the retrieval of words from the mental lexicon. The task required subjects to resolve fragmented words when provided with semantically related cues (e.g., spiteful:---DIC----). Phonological properties of the letter cues were manipulated such that the letters either corresponded to the syllables (e.g., DIC in vindictive) or nonsyllables (NDI) in the word. Orthographic properties of the letter cues were manipulated by selecting letter groups that either co-occurred frequently in the language or did not. In two experiments, results revealed little or no effect of the phonological variable (syllables) but a reliable effect of the orthographic variable (letter-cue frequency). Letter cues with a low frequency of co-occurrence in the language led to better completion of the fragmented words. We interpret these findings as support for models of lexical representation that are based on orthographic properties (e.g., Seidenberg & McClelland, 1989) rather than those based on phonological constraints.


Word frequency effects in associative and item recognition.

The word frequency effect (WFE) has been taken as evidence that recall and recognition are in some way fundamentally different. Consequently, most models assume that recall and recognition operate via very different retrieval mechanisms. Experiment 1 showed that the WFE reverses for associative recognition, which requires discrimination between intact test pairs and recombinations of study list words from different study pairs. Experiment 2, in which word triples were used, revealed an interaction between word frequency and test type: for item recognition, performance was better for low-frequency words; however, for associative recognition and free recall, performance was better for high-frequency words. In Experiment 3, item recognition was tested: although overall performance was better for low-frequency words, the recognition advantage for items in intact pairs was larger for high-frequency words, suggesting two components in recognition memory. These results imply common mechanisms in recall and recognition. Theoretical implications are discussed within the framework of the SAM model.


Age-related differences in the specificity of verbal encoding.

A communication paradigm was used as an analogue to cued recall to separate age-related differences in encoding and retrieval. Younger and older adults (senders) generated a series of one-word clues that would enable other subjects (receivers) to generate a designated target word. Clue and target generation tasks, analogous to the encoding and retrieval components of cued recall, were conducted in the context of either a strong or a weak associate of the target. Clues generated by older senders were less effective than clues generated by younger senders in enabling receivers to generate targets, especially when clues or targets were generated in the context of a weak associate. A deficit among older receivers was also obtained, especially when a weak-rather than a strong-associate context word was given to the receiver. Older adults experience difficulty with encoding and retrieval tasks that require processing of context-specific information that is not part of the generic information typically associated with a stimulus.


The discriminability of remembered magnitudes.

Psychometric functions and the associated indices of discriminative performance (i.e., the point of subjective equality [PSE], just noticeable difference, and Weber fraction) were obtained with the method of constant stimuli using perceptual and remembered line-length standards. Three important results were obtained. First, comparisons with a perceptual or a remembered standard were sensitive to variations of absolute stimulus differences with a common ratio; that is, Weber's law was violated. Second, relative to discriminative performance with the longest and shortest remembered standards, comparisons involving mid-range remembered standards displayed increased variability in the PSE and inflated Weber fractions, characteristic of a reduction in the quality of the memorial representation. Finally, large and negative time-order errors (TOE) were observed for successive line judgments but not for those involving remembered standards. The implications of these findings for research concerned with the relationships between perception and memory, as well as the TOE phenomenon, are discussed.


Hemispheric specialization for categorical and coordinate spatial representations: a reappraisal.

The purpose of the present study was to examine Kosslyn's (1987) claim that the left hemisphere (LH) is specialized for the computation of categorical spatial representations and that the right hemisphere (RH) is specialized for the computation of coordinate spatial representations. Categorical representations involve making judgements about the relative position of the components of a visual stimulus (e.g., whether one component is above/below another). Coordinate representations involve calibrating absolute distances between the components of a visual stimulus (e.g., whether one component is within 5 mm of another). Thirty-two male and 32 female undergraduates were administered two versions of a categorical or a coordinate task over three blocks of 36 trials. Within each block, items were presented to the right visual field-left hemisphere (RVF-LH), the left visual field-right hemisphere (LVF-RH), or a centralized position. Overall, results were more supportive of Kosslyn's assertions concerning the role played by the RH in the computation of spatial representations. Specifically, subjects displayed an LVF-RH advantage when performing both versions of the coordinate task. The LVF-RH advantage on the coordinate task, however, was confirmed to the first block of trials. Finally, it was found that males were more likely than females to display faster reaction times (RTs) on coordinate tasks, slower RTs on categorical tasks, and an LVF-RH advantage in computing coordinate tasks.


Remembering emotional events.

Recent experiments have implied that emotional arousal causes a narrowing of attention and, therefore, impoverished memory encoding. In contrast, other studies have found that emotional arousal enhances memory for all aspects of an event. We report two experiments investigating whether these differing results are due to the different retention intervals employed in past studies or to their different categorization schemes for the to-be-remembered material. Our results indicate a small role for retention interval in moderating emotion's effects on memory. However, emotion had markedly different impacts on different types of material: Emotion improved memory for gist and basic-level visual information and for plot-irrelevant details associated, both temporally and spatially, with the event's center. In contrast, emotion undermined memory for details not associated with the event's center. The mechanisms for emotion's effects are discussed.


Familiarity, memorability, and the effect of typicality on the recognition of faces.

Typical faces are more poorly discriminated on tests of recognition than are atypical faces, an effect suggested to mediate similar findings for attractive or likable faces. We tested the hypothesis that the effect of typicality on recognition is a function of context-free familiarity and memorability, which function in opposition. Two orthogonal principal components were extracted from subjects' ratings of faces for typicality, familiarity, attractiveness, likability, and memorability--one consisting of the ratings of familiarity, attractiveness, and likability, and reflecting context-free familiarity, and the other consisting of the memorability rating. As expected, typicality loaded equally (r approximately .66), but with opposite sign, on both components. In subsequent experiments, both components were found to be significant and additive predictors of face recognition with no residual effect of typicality. General familiarity decreased discrimination, and the memorability component enhanced it, supporting the hypothesis. The results are discussed in terms of the mirror effect.


Semantic priming in the pronunciation of words in two writing systems: Italian and English.

Semantic priming effects in naming Italian and English words were investigated. Experiments 1 and 2 were in Italian. In Experiment 1, the subjects named a target word, which was either associated with or unrelated to a preceding prime. The results showed semantic priming effects. However, in Experiment 2, in which the same materials occurred in a list that also included pseudowords, priming effects were obtained with the lexical decision task, but not with pronunciation. In Experiment 3, the inclusion of pseudowords in the materials prevented priming effects from occurring in Italian, but not in English. Finally, Experiment 4 indicated that, even in Italian, nonlexical reading was abandoned when a few of the to-be-pronounced items required lexical knowledge for correct stress assignment. The findings suggest that reading normally occurs lexically. The characteristics of the various writing systems, however, are relevant in determining the strategies that people may adopt in unusual circumstances.


Interference in memory for tonal pitch: implications for a working-memory model.

The degree of interference caused by different kinds of stimuli on memory for tonal pitch was studied. Musically trained and untrained subjects heard a sequence of two tones separated by an interval of 5 sec. The tones were either identical in pitch or differed by a semitone. Subjects had to decide whether the tones were identical or not. The interval was filled with tonal, verbal, or visual material under attended and unattended conditions. The results revealed clear group differences. Musically trained subjects' retention of the first test tone was only affected by the interposition of other tones. In contrast, the performance of musically untrained subjects was also affected by verbal and visual items. The findings are discussed in the framework of Baddeley's (1986) working-memory model.


Consistency of perimenopausal estrogen use reporting by women in a population-based prospective study.

The authors assessed the accuracy of perimenopausal estrogen use reporting by 430 women in a prospective study of bone health risk factors. Data from two time points 5 years apart indicated that 383 (89%) women could consistently report having ever used perimenopausal estrogens or not. Of the 383, 138 reported some lifetime perimenopausal estrogen use; 97 (70%) of these consistently reported duration of use. The age-adjusted relative odds that women would misreport having ever used perimenopausal estrogens was 11.7 (1.3, 100.6) for women with 11-20 years since last use, and 22.2 (1.8, 277.4) for 21+ years. Among women who inconsistently reported ever use of perimenopausal estrogen, the relative odds of reporting use at baseline and never use at follow-up as compared to reporting the converse by women aged 70-75 was 8.1 (1.2, 53.2) times that for women aged 60-69 at follow-up, and increased to 9.6 (1.8, 49.9) for women aged 76-85. This suggests that women can consistently report perimenopausal estrogen use, but accurate report of use declines in women whose last use precedes the interview by over 10 years. Accurate report of duration or dates of perimenopausal estrogen use may be compromised in women of more advanced age.


Effects of vaginally-administered oestriol on post-menopausal urogenital disorders: a cytohormonal study.

Forty post-menopausal women with urogenital disorders who were inpatients in the same geriatric hospital were treated with oestriol (E3) for 6 weeks. For the first 2 weeks 0.5 mg E3 (Leo AB, Sweden) was administered intravaginally every day. Over the following 4 weeks the patients received the same quantity either once or twice weekly as a maintenance dose. Oestrogen influence on the vaginal and urethral epithelium was assessed by means of the karyopyknotic index (KPI), while the degree of maturation of the vaginal epithelium was estimated visually. Urinary bacteria were cultivated. A pronounced and progressive rise in KPI was seen in both the vaginal and the urethral epithelium following daily E3 treatment. However, neither of the two maintenance dosages was sufficient to sustain the initial maturation of the vaginal and urethral epithelium induced by E3, since the KPI returned to pretreatment values within 4 weeks. The effect of E3 administration on the vaginal epithelium was overestimated by the visual assessment method. No changes were seen in urinary bacteria. Medroxyprogesterone acetate was given before and after E3 treatment. None of the women suffered from withdrawal bleeding.


Effect of fever on menopausal hot flashes.

Some women report that they have fewer hot flashes when they have a fever. This is the first case of physiological monitoring of hot flashes during fever in a subject with a well documented pattern of frequent hot flashes when afebrile. During fever, there were fewer hot flashes than during afebrile periods, and these hot flashes also tended to be less intense. For most of the period of reduced hot flashes, internal (core) temperature was elevated, above 37.5 degrees C. When the fever broke, hot flashes resumed in a pattern similar to that of afebrile periods. Possible explanations for the reduction in hot flashes during a fever include: (1) a hot flash is triggered, but the characteristic physiological changes do not occur due to competing thermoregulatory drives, (2) the febrile core temperature inhibits whatever it is that triggers a hot flash; or (3) some product of the fever process inhibits the hot flash trigger or masks the physiological changes that occur during hot flashes.


Short term effects of SHD 386L and levonorgestrel on bone and mineral metabolism in the postmenopause: a double-blind randomised placebo-controlled trial.

Forty-five healthy postmenopausal women participated in a study designed to examine the effects on bone and mineral metabolism of SHD 386L, a new hormone replacement therapy (HRT) regime. This oral preparation delivers 2 mg estradiol valerate daily and 75 micrograms of levonorgestrel from days 17-28 inclusive of a 28-day cycle. The study was double-blind, randomized and placebo controlled. Patients who received SHD 386L exhibited significant falls in plasma calcium, ionised calcium, phosphate and total alkaline phosphatase. No alteration, however, was observed in plasma osteocalcin. No significant changes in mineral metabolism were observed in a parallel group receiving levonorgestrel alone. The results indicate that SHD 386L is likely to be protective to the skeleton through inhibition of bone resorption and that such actions are attributable to the estrogen component. The preparation was well tolerated, compliance was satisfactory and serious adverse affects were not seen. The above biochemical evidence for skeletal protection will require to be supplemented by prospective biophysical evidence of the effect of SHD 386L on bone mineral density.


A new methodological approach to the evaluation of quality of life in postmenopausal women.

An approach employing a range of standardized questionnaires, which included the Nottingham Health Profile (NHP), the Psychological General Well-Being (PGWB) index and the Mood Adjective Check List (MACL), was used to assess health-related quality of life (QoL) in conjunction with a study comparing two doses of transdermal oestrogen (50 or 100 micrograms/24 h) combined with an oral progestogen (5 mg medroxyprogesterone acetate for 14 days each cycle). In addition to the QoL measures, climacteric symptoms were self-rated and also summarized by means of the Kupperman index. In all, 59 women, median age 52 (39-71) years, who completed 4 months of therapy were evaluated. The use of a battery of standardized questionnaires enabled a comprehensive evaluation to be made of perceived health, well-being and day-to-day functioning. Not only was symptomatic relief, e.g. reduced frequency of sweating episodes, sleep disturbance and hot flushes, observed during treatment, but there were also improvements in terms of sleep, energy and emotions. The frequency of health-related problems associated with paid employment, housework, social life, home life and sex life decreased, indicating enhanced ability to take part in daily activities. The PGWB index showed improvement in the subscales representing well-being, anxiety, depression, vitality, health and self-control, while the mood scales indicated that the women experienced less tension and more satisfaction. Although the results of this study need to be further documented on the basis of a placebo-controlled trial, the findings nevertheless imply that the use of a battery of standardized questionnaires optimizes the possibility of evaluating climacteric complaints reliably before and after treatment.


Long-term effect of transdermal hormonal therapy on aspects of quality of life in postmenopausal women.

The long-term effect on aspects of quality of life (QoL) of treatment with transdermal oestrogen for 2 weeks followed by transdermal oestrogen/progestogen norethisterone acetate/oestradiol TTS 0.25/0.05 mg/day for the next 2 weeks was investigated in postmenopausal women within the framework of a 1-year seven-centre trial. Of the 136 women who were included (mean age 53 +/- 4.8 years), 110 completed the study. Aspects of QoL that are of relevance in the perimenopause and postmenopause were evaluated using the Psychological General Well-Being (PGWB) index, the Women's Health Questionnaire (WHQ) and the Sleep Dysfunction Scale before and after 3 and 9 months of therapy in the oestrogen phase. Climacteric complaints were also assessed by means of the Kupperman Index. Improved well-being, i.e. less anxiety and depression, increased vitality and better self-control (P less than 0.0001) were observed, as well as reduced sleep disturbance (P less than 0.0001). The WHQ showed decreased vasomotor and somatic symptoms, and improved sex life, emotions and cognitive function (P less than 0.0001). Improvement was the same at 3 and 9 months. According to the Kupperman Index, climacteric symptoms were alleviated (P less than 0.0001). Relief of vasomotor symptoms was correlated with improvement in the WHQ (r = 0.82), the PGWB index (r = 0.58, P less than 0.0001) and sleep (r = 0.51, P less than 0.0001). Because of the absence of a placebo control group, the results must be regarded with caution until confirmed in a placebo-controlled trial.


[A comparison of the level of resistance and irritability in Anopheles hyrcanus and An. superpictus to insecticides].

The resistance and irritability to malathion, fenitrothion, propoxur and DDT (WHO insecticide impregnated paper) were determined in the endophilic Anopheles superpictus population in Dushanbe and in the exophilic An. hyrcanus population in Parkhar district. An. superpictus proved to be completely susceptible to malathion, fenitrothion and propoxur, low resistant to DDT, and highly or moderately irritable to all the insecticides. On the contrary, An. hyrcanus, was low irritable to insecticides but highly resistant to DDT and moderately resistant to propoxur, while its susceptibility to malathion and fenitrothion remained complete. It is supposed that the nature of adaptation to insecticide pressure is, to a great extent, determined by mosquito endophily or exophily.


[Variability in scabies mites Sarcoptes scabiei De Geer (Acariformes, Sarcoptidae) in relation to scabies epidemiology. 1. A statistical model of female variability].

Individual variability of 235 grain mite females from Moscow and the Moscow Province was studied. The data were processed on a computer. Body proportions were used as a representative dimension index. The size of proterosomal scutellum was stable. A map of the chaetoid cover of notum is given, and its variability was studied. Statistical analysis of all signs was made. Frontal chaetoid and sejugal sections and the number of caudal chaetoids are stable. Naked, middle and abdominal chaetoid sections are the most variable. Linear sizes of naked section and the number of chaetoid sets on middle and abdominal sections correlate with the number of undeveloped chaetoids. The statistical model of variability may be useful for populational analysis of Sarcoptes forms in connection with scab epidemiology.


[The insecticidal action of the synthetic pyrethroid Decis on the rodent flea].

A new aspect of insecticide action of synthetic pyrethroid "Decis" as a system poison for wild rodent flea control is discussed. Rapid decay of the insecticide gives an opportunity to use it in grain baits in the natural foci of plague.


[The ecology of Echinococcus multilocularis (Leuckart, 1863) and E. granulosus (Batsch, 1786) on the Kamchatka Peninsula].

Some aspects of dwelling of Echinococcus multilocularis and E. granulosus populations in the Kamchatka Peninsula were considered. Transformation of their natural foci to natural synanthropic due to enrichment of mammalian fauna, increased human density and rural development was noticed. Main quantitative characteristics of infectivity of the worm definitive and intermediate hosts are presented using literature and the author's own data. A correlation was noted between host density and their infectivity with Echinococcus.


[The efficacy of Vermox and albendazole in an experimental model of nippostrongylosis in mice].

Experiments with the model of Nippostrongylus brasiliensis and white outbred mice showed that vermox and albendazole are highly effective anthelmintics in nippostrongyliasis. The ED50 of albendazole for 7 days invasion (adult worms) is 148.9 times higher than for 4 days (fourth instar larvae) and 25.1 times higher than for 2 days (third instar larvae). The ED90/ED10 ratio for albendazole is 1.4, 4.4, and 12.4 at days 7, 4, and 2, respectively. At the adult stage, susceptibility to anthelmintics (vermox and albendazole) increases with age.


[The search for new antiparasitic agents. 10. The synthesis, toxicological and antimalarial properties of nitrogen-containing heterocycles with a 4-(4-alkylpiperazinyl-1) phenylamine substituent (the preparation quinoprazine)].

Synthesis is described and acute toxicity and antimalaria action is studied in new derivatives of quinoline and benzo(g)quinoline containing a 4-(4-alkylpiperazinyl-1)phenylamine substitute. Only the derivatives of benzo(g)quinoline were found to have a high antimalaria effect and to have advantages over the standard agent chloroquine on their tolerance and protective action. One of the compounds, 4-[4-(4-ethylpiperazinyl-1)phenylamino] benzo(g)quinoline, named QUINOPRAZINE, showed some action against Plasmodium berghei chloroquine--resistant infection (isolate LN-K65). This agent was elected for further tests.


[Data on the spread of Culex pipiens on the territory of the USSR].

A map of Culex pipiens molestus distribution over the USSR was made using data of sanitary epidemiological stations of various regions of the country, literature and the authors' own data. It was shown that during the last decades (1978-1990) the Cx. p. molestus breeding occurring predominantly in flooded basements of comfortable houses, especially in new built towns and cities, was recorded throughout the European part of the USSR including some subarctic regions. Cx. p. molestus is also widespread in the Asiatic part of the country including Western and Eastern Siberia, southern regions of Far East and the Sakhalin Island and Kamchatka. In the permafrost areas, most of new houses are built on piles without basements and cellars, and it prevents Cx. p. molestus breeding. The dates of appearance of these mosquitos in various parts of the country due to the development of transportation are discussed.


[Experience with the diagnosis of taeniarhynchiasis caused by the northern isolate of the beef tapeworm by B. E. Rabinovich's method].

It has been shown that the method of B. E. Rabinovich may be used for the diagnosis of infestation caused by the northern isolate of Taeniorhynchus. Bearing in mind biological specificities of the above helminth species, to enhance the efficacy of diagnostics it is advisable to use the technique in combination with the method of Kato.


A digital-radiographic technique for in vitro tissue thickness measurement using iodine displacement.

A novel digital radiographic method has been developed for measuring the thickness of a tissue sample by iodine displacement. This simple, accurate method is useful both in medical research and in the comparison of pathological and clinical findings. Radiographic measurements of tissue samples in air suffer from the limitation that the quantity measured depends on the product of both thickness and radiographic attenuation coefficient. This technique allows one to obtain thickness measurements from a digital radiograph of a tissue sample suspended in a bath of radio-opaque contrast agent. The attenuation of the iodinated contrast agent is much higher than that of tissue or calcium. Thus the resulting image is determined largely by the contour of the surrounding bath, and is only slightly influenced by the composition of the tissue. This technique improves both the accuracy and precision of radiographic thickness determination. In this paper the iodine displacement technique is described and the accuracy and precision of thickness measurements in appropriate phantoms are quantified. This technique has been used with both image intensifier and screen-film based imaging systems to obtain thickness maps of calcified human aorta, with precision better than 4% and spatial resolution of 2.5 mm-1.


A review of the processes by which ultrasound is generated through the interaction of ionizing radiation and irradiated materials: some possible applications.

The production of acoustic waves following the absorption of energy deposited by ionizing radiation, with a consequent production of localized thermal spikes has been confirmed by a number of papers published in the physics literature. This paper reviews the basic theory and presents most of the supporting experimental data. Some of the experimental methods used and the results obtained are summarized. In addition to the rather straightforward and routine use of acoustic phenomena produced by ionizing radiation for the detection and measurements of such radiation, there are some special applications that appear to be especially attractive for medical physics. Some of these are unique to ionizing radiation in that the amplitude of the ultrasound wave is proportional to the energy deposited in small volumes at localized sites of these interactions, while others derive from methodologies already in use with nonionizing radiations. The detection and measurement of this ultrasonic radiation could possibly lead to methods for the study of such fundamental phenomenon as track structure, precision localization of therapeutic treatment beams, and even the possible imaging of internal anatomic structures to provide on-line portal images.


Considerations regarding the application of capillary optics to medical radiography.

The generation of monoenergetic or quasimonoenergetic x-ray spectra has been accomplished by several methods including the use of K-edge filtration, characteristic radiation, crystal monochromators, and multilayer mirrors. In this paper some practical questions are discussed regarding the possibility of obtaining narrow-band spectra using x-ray reflection in glass capillary optics which have been reported recently in connection with the focusing and generation of parallel x-ray beams. Derivation of formulas for double and triple reflection with and without additional K-edge filtration imply that these methods are superior to the use of filtration alone. It is shown that the double reflection scheme is most sensitive to the angular divergence of the beam emanating from the capillary array used to generate the incident parallel beam. Simulations using three reflections predict output spectra which are relatively insensitive to blurring due to angular divergence. A small amount of K-edge filtration in combination with three reflections provides considerable sharpening of the x-ray spectrum. Aside from the spectral selectivity provided by the capillary array, the reduced divergence of the primary transmission may have advantages for scatter rejection in situations where the air gap between the patient and detector is increased by an amount consistent with the resolution requirements of the application. In parallel beam situations, the use of capillary arrays between the patient and detector may also be useful for the rejection of divergent scattered radiation.


Computerized detection of clustered microcalcifications in digital mammograms: applications of artificial neural networks.

Artificial neural networks have been applied to the differentiation of actual "true" clusters from normal parenchymal patterns and also to the differentiation of actual clusters from false-positive clusters as reported by a computerized scheme for the detection of microcalcifications in digital mammograms. The differentiation was carried out in both the spatial and frequency domains. The performance of the neural networks was evaluated quantitatively by means of receiver operating characteristic (ROC) analysis. It was found that the networks could distinguish clustered microcalcifications from normal nonclustered areas in the frequency domain, and that they could eliminate approximately 50% of false-positive clusters of microcalcifications while preserving 95% of the positive clusters, when applied to the results of the automated detection scheme. A large, comprehensive training database is needed for neural networks to perform reliably in clinical situations.


High-contrast resolution of CT images for bone structure analysis.

The modulation transfer function (MTF) of an imaging system may be used as a figure of merit to assess its geometrical resolution. As such it is often derived from the point spread function (PSF) through a Fourier transformation, or through a FFT in case of digital images. Using the special features of the convolution-backprojection algorithm and making some simplifying assumptions about the number of rays, it is shown that the desired MTF is also obtainable without a Fourier transformation of the PSF, different shapes and sizes of the beam-profile are then analyzed, and finally it is shown that calculated and measured MTF functions are in good agreement. The effects of aliasing on the cutoff frequency are also discussed.


Two thermal methods to measure the energy fluence of a brief exposure of diagnostic x rays.

This paper describes two simple thermal methods for measuring the energy fluence in J/cm2 from a diagnostic x-ray exposure. Both detectors absorb essentially 100% of the radiation and give a signal that is directly proportional to the energy fluence of the x-ray beam. One detector measures the thermal effect when a pulse of x rays is totally absorbed in the pyroelectric detector of lead-zirconium-titanate (PZT). The other detector measures the expansion of a gas surrounding a lead disk detector in a photoacoustic chamber. The increased pressure of the gas is transmitted through a 1-mm duct to a sensitive microphone. Both detectors have previously been used to measure the energy fluence rate of continuous x-ray beams in the same energy region using a chopped beam and a lock-in amplifier. Measurement of the energy fluence of a pulse of radiation eliminates the need for the beam chopper and lock-in amplifier and results in a simple, rugged, and inexpensive dosimeter. Either method can be combined with the area of the beam to give an estimate of the imparted energy to the patient from a diagnostic x-ray exposure.


Evaluation of video gray-scale display.

Setting up and maintaining video display monitors properly will help to reduce display variation and improve overall presentation of the radiological image. Display monitor gray-scale characteristics were examined using the SMPTE test pattern. This test pattern may be used as a standard for adjusting brightness and contrast. The controls should be adjusted to display the full dynamic range so that the 5% and 95% signal levels in the pattern are visible. Measured luminance on a laboratory workstation used for radiological perceptual experiments, and on the Siemens CT gray-scale monitor was determined to range from 0.17 to 76.0 nit, and 0.17 to 24.66 nit, respectively. These were compared with the range of approximately 17 to 514 nit for a typical film-viewbox combination. Characteristic curves were determined for both monitors, and CRT gammas were 3.34 and 2.48 for the perceptual workstation and CT console, respectively. The display gamma was determined from fitting luminance data to a log-log plot of luminance versus input gray level. The usefulness of the SMPTE test pattern for visual presentation as well as photometric measurement is demonstrated.


Two new experimental methods of calculating scatter fraction as a function of depth in scattering media: a comparison study.

Two new experimental methods of calculating scatter fraction (SF), as a function of depth, are presented and used in a comparison study. These methods are based on the assumptions that the total point spread function (psft) consists of geometrical (psfg) and scattering (psfs) components, and that the psft and its components are radially symmetric functions. Both methods assume that psfg is a two-dimensional (2-D) Gaussian function. The first proposed method is based on the serial model of the psft. According to the serial model, psfs is also a 2-D Gaussian function. However, the second method is based on the assumption that the psfs is a monoexponential function. Thus the main difference between these two experimental methods is the way in which the psfs is treated. Published data obtained by Monte Carlo simulations compared to the new experimental results shows that for depths less than 5 cm, both new methods yield smaller values for scatter fraction than Monte Carlo simulation or the subtraction method. However, for depths from 5 to 20 cm, the results of these two new methods were very close to the values obtained by both the Monte Carlo simulation and the subtraction method. These two methods have allowed assessment of the scatter fraction with higher accuracy and reliability and reporting data concludes that the new methods are less error sensitive than the subtraction method.


A comparison of semiempirical models for generating tungsten target x-ray spectra.

Models for the computer generation of tungsten target x-ray spectra proposed by Birch and Marshall [Phys. Med. Biol. 24, 505-517 (1979)] and recently by Tucker, Barnes, and Chakraborty [Med. Phys. 18 211-218 (1991)] are compared. Some basic differences in the equations for the number of bremsstrahlung photons of different energies in the spectra are discussed. The models are compared in terms of their ability to characterize x-ray spectra from constant potential clinical units using three parameter equivalent spectra (EQSPEC) determined from the fit of model generated transmission curves through aluminum to measured data. The Kramers model for x-ray generation is included for completeness. It is shown that two of the models generate very similar x-ray spectra from given transmission curves although the fitting parameters in the EQSPEC characterization differ.


Distributed self-capacitance of magnetic resonance imaging birdcage coils.

Presented is a theoretical description of the self-capacitance of a low-pass birdcage coil. The problem considered is that the modification of the distributed self-capacitance produced by the electric interaction between the coil and a cylindrical Faraday screen and illustrates the phenomenon of coil self-capacitance as well as the influence of Faraday screens. Changes in coil self-capacitance produced by the presence of the screens are shown to be consistent with measured shifts in coil resonant frequencies.


A new x-ray and light field superimposition detector.

A fast and accurate method to determine the alignment of the diagnostic x-ray and light fields was developed. Following the exposure, the boundaries of an x-ray field are determined by a custom-built x-ray field position detector and indicated by light-emitting diodes. The alignment of the supposed and the actual x-ray fields agree (within +/- 2 mm) with the corresponding results of the film-based procedure.


The enhancement of radiotherapy verification images by an automated edge detection technique.

Adaptive histogram equalization techniques are known to be effective for the enhancement of contrast in portal images acquired during radiotherapy treatments. A significant drawback is the loss of definition on the edges of the treatment field. Analysis of this problem shows that it can be remedied by separating the treatment field from the background prior to the enhancement, and using only the pixels within the field boundary in the enhancement procedure. An edge extraction algorithm has been developed for delineating the treatment field in portal images, and consists of four modules that are applied to the original portal image in sequence. In the first step, edges are enhanced with a derivative of Gaussian operator that assures high response to the field edges relative to anatomical or other edges in the image. Pixels for which the response of the edge operator was the strongest are subsequently connected by an edge following algorithm to produce a raw contour of the field. In the last two steps the contour is refined by converting it into straight line segments and appending to the contour any parts of the field edge that might have been missed out during the initial edge following. The final contour encloses exclusively those pixels that belong to the treatment field, and the adaptive histogram equalization is applied selectively to this region. The combination of edge detection and selective enhancement was shown to produce images of superior contrast on the patient's anatomical features as well as accurate definition of treatment field edges.


A fast and accurate algorithm for volume determination in MRI.

The determination of volumes in clinical MRI studies are prohibitive because of the time required to compute an accurate volume. Techniques that speed up the calculation are prone to large errors which make most impractical for an accurate diagnosis. A linear filter, called the eigenimage filter, has been developed that separates a desired feature from other features which interfere with its observation in an image. Using the images produced by this technique (eigenimages), the amount of operator interaction required to calculate volumes are significantly reduced. The technique also has the ability to correct for partial volume averaging effects and as a result a more accurate volume can be determined. The technique was applied to a computer simulation and two phantom studies. The time required to calculate the volume was less than 1 min per slice and the errors in accuracy and reproducibility were less than 2% for all studies.


Pretransfusion blood irradiation: clinical rationale and dosimetric considerations.

The irradiation of blood before transfusion into immunosuppressed patients is an increasingly common technique used to prevent graft-versus-host disease. A technical procedure is described for the calibration of blood irradiators, including the determination of absolute dose rate and relative dose distribution over the blood volume. Results of dose rate measurements on commercially available irradiators indicate differences of +5% to -13% with manufacturer-supplied calibrations and variations in the relative dose rate over the irradiation volume from 70% to 180%. The clinical implications of these findings and the need for accurate dosimetry are discussed.


Design of parallel plate ion chambers for buildup measurements in megavoltage photon beams.

Dose measurements in the buildup region of megavoltage photon beams are most commonly made using parallel plate ion chambers having fixed electrode separation. Fixed-separation chambers generally do not read correctly under such beam conditions because of the contribution to the chamber signal of electrons from the side walls. In this work it is shown that the side wall error can be very large and published correction formulas are not accurate for all beam conditions and chamber geometries. The principal focus of this study has been to determine the design features of a fixed-separation chamber that has negligible side wall error. The approach has been to study, in beams of 60Co, 6 MV, and 18 MV, the response of a specially built ion chamber in which several chamber parameters could be independently varied. The study has shown that the side wall error is primarily dependent on the ratio of the electrode separation to the wall diameter as well as on the wall density and wall angle. Based on these findings the design of a fixed-separation chamber is described which reads to within about 1% of the correct dose. Guidelines are also provided for assessing the suitability of current commercial fixed-separation ion chambers for buildup measurements.


Polarity effect in plane-parallel ionization chambers using air or a dielectric liquid as ionization medium.

A plane-parallel ionization chamber having a sensitive volume of 2 mm3 and using the dielectric liquid tetramethylsilane as the sensitive medium instead of air is described. In the design of the chamber special attention was given to the factors that can cause unwanted currents in the cable, stem, or the chamber dielectric material. The chamber has been tested with respect to the polarity effect in regions of radiation fields where ordinary plane-parallel ionization chambers will often fail. These regions are the build-up region in photon fields, and the region close to the practical range for electrons where nonelectronic equilibrium is significant. Experimental results show that, despite the extremely small ionization volume in the liquid ionization chamber, the polarity effect never exceeds a few tenths of a percent in field positions where well-known commercially available chambers with much less spatial resolution designed for measurements in radiation therapy fields can show polarity effects of 5% to 30%. The origin of spurious currents and how they must be minimized in the design of either a liquid- or gas-filled ionization chamber is discussed.


Verification data for electron beam dose algorithms.

The Collaborative Working Group (CWG) of the National Cancer Institute (NCI) electron beam treatment planning contract has performed a set of 14 experiments that measured dose distributions for 28 unique beam-phantom configurations that simulated various patient anatomic structures and beam geometries. Multiple dose distributions were measured with film or diode detectors for each configuration, resulting in 78, 2-D planar dose distributions and one, 1-D depth-dose distribution. Measurements were made for 9- and 20-MeV electron beams, using primarily 6 x 6- and 15 x 15-cm applicators at several SSDs. Dose distributions were measured for shaped fields, irregular surfaces, and inhomogeneities (1-D, 2-D, and 3-D), which were designed to simulate many clinical electron treatments. The data were corrected for asymmetries, and normalized in an absolute manner. This set of measured data can be used for verification of electron beam dose algorithms and is available to others for that purpose.


On the spatial resolution of clinical thermometers.

In this work the spatial resolution of type T (copper-Constantan) and type K (Chromel-Alumel) multipoint thermocouple thermometers was investigated. For clinical use, thermocouples are usually inserted within catheters to provide easy access, reproducibility, and a sterile environment. The effect of several types of catheter on the ability of these thermometers to accurately resolve thermal gradients was studied. The influence of the number of wire pairs within the multipoint thermometer was also investigated. A mathematical model has been developed to determine the spatial resolving power of these thermometers. Results indicate that type K thermocouples are generally superior to type T and the use of catheters plays a significant role in spatial resolution. Moreover, the use of mineral oil as a thermal coupling agent between the catheter and the thermometer was also found to have some effect.


Measurement of the source size of a 6- and 18-MV radiotherapy linac.

The quality of portal imaging is strongly affected by the source size of the radiotherapy machine. The effective source size of the dual-energy clinac 1800 (6 and 18 MV) was measured with a 50 microns wide and 120 mm long slit formed by two tungsten-copper alloy blocks. A series of slit images were obtained by translating the slit horizontally. The images were analyzed using a microdensitometer. The measured data was simulated using an analytical model of the source and its size was derived by a best-fit analysis. For both energies the FWHM was found to be 1.5 +/- 0.1 mm.


Head-scatter factors and effective x-ray source positions in a 25-MV linear accelerator.

The behavior of the effective source position and the correction factor associated with the collimator opening (head-scatter factor) were investigated for the 6- and 25-MV x-ray beams of a linear accelerator. The primary photon fluence was measured in air for square field sizes from 5 x 5 cm to 40 x 40 cm at distances from the nominal source of 80 to 140 cm, for open and wedged fields (wedge angle 60 deg). An inverse-square analysis shows that, for open fields, the effective source position of the accelerator is about the same (approximately 1 cm downstream) at 6 and 25 MV, for all field sizes. For the wedged fields, the effective source position depends on field size and ranges from about 2 to 4 cm. The head-scatter correction factors for given collimator settings were found to be essentially independent of distance at both energies.


[Long-term follow-up of thrombolytic treatment of acute infarct in combination with acute and elective revascularization].

From March 1983 to June 1986 in 206 patients with acute transmural myocardial infarction, combined intravenous and intracoronary therapy with streptokinase was initiated. After intravenous thrombolysis and randomization in two groups we performed a coronary angiography with selective intracoronary lysis. Infarct related vessels still occluded after intracoronary streptokinase application were opened mechanically in group I. In group II we performed additionally a percutaneous transluminal coronary angioplasty (PTCA) after mechanical recanalisation (occluded vessels) or after thrombolysis (open vessels). In 85 of 87 cases in group II, PTCA could be performed in the acute phase. Elective PTCA was performed in 22 patients of group I (21%) and in nine patients of group II (9%). Up to five years after myocardial infarction, coronary artery bypass grafting (CABG) was necessary in 22 patients (21%) of group I and in 23 patients (22%) of group II. Within four weeks after infarction CABG was performed in 32% and 17% of group I and II respectively. The six-year survival rate was 78% in group I and 82% in group II. Taken all patients together, the six-year survival rate was significantly higher (p = 0.002) for those with early reperfusion (less than or equal to 3.5 h). The survival rates of CABG-patients, PTCA-patients and patients without reperfusion were 91%, 74% and 65% respectively. Streptokinase thrombolysis results, combined with acute or elective PTCA and/or coronary bypass surgery, in a high six-year survival rate after acute transmural myocardial infarction. This rate is about 20% higher than ten years ago.


Dosimetry of ruthenium-106 eye applicators.

In view of the importance of clinical applications of ruthenium-106 beta-ray sources for the treatment of choroidal melanoma, experimental, and theoretical approaches are presented for the dosimetry of such sources. The absolute dose and percentage depth dose of ruthenium applicators have been measured with an extrapolation ionization chamber. For a special flat applicator the absolute dose could be measured with an accuracy of +/- 5%, which is determined by the collection efficiency of the extrapolation chamber. The percentage depth dose of concave applicators, employed in the clinical situation, could only be measured at a distance larger than 5 mm due to their geometry and the outer dimensions of the extrapolation chamber. A computer simulation was therefore developed for the absorption and scattering of electrons, taking into account the geometry and materials of the applicator, to predict the percentage depth dose at distances smaller than 5 mm. The calculated and experimentally determined depth doses are in good agreement. With the aid of the computer simulation a depth dose determination for concave applicators can be made for clinically relevant distances less than 10 mm from the source surface with an absolute accuracy of +/- 10%.


[Long-term therapy of cystic liver echinococcosis with mebendazole].

Surgery is the therapy of choice in the treatment of infestations with Echinococcus (E.) granulosus and E. multilocularis. Chemotherapy with mebendazole, a benzimidazole derivative, introduced 1976 in the therapy of human echinococcosis, showed good results only in cases of infestation with E. multilocularis. In the cases of liver cysts, caused by E. granulosus, the treatment with mebendazole did not succeed as well. Between 1977 and 1986, 44 patients, suffering from infestations with E. granulosus, were referred to the Clinical Department of the Bernhard-Nocht-Institut. In a retrospective study, the data of seven patients had been evaluated: They had not undergone surgery because of the size of the lesions or because they refused the operative treatment. Receiving mebendazole as the only therapy, they had been treated and followed up for more than four years. Mebendazole was given in a dosage of 50 mg/kg body weight in repeated cycles of one month's duration followed by a treatment-free interval of two months. After a median of 55 months (median 13 effective treatment months) six of the seven patients presented a therapeutical success as demonstrated by ultrasound and computed tomography. The cystic lesions had dissolved or decreased in size considerably. One case showed unaltered findings of the liver lesion. Mebendazole treatment was well tolerated by all patients. If the size of the cystic liver-lesions excludes a curative operative treatment or if the patient refuses surgery, the indication for chemotherapy with mebendazole is given.


Ytterbium-169: calculated physical properties of a new radiation source for brachytherapy.

Seeds containing radioactive Ytterbium-169 (169Yb) have recently been manufactured for possible application to brachytherapy. Ytterbium-169 emits photons with an average energy of 93 keV (excluding energies less than 10 keV), and decays with a half-life of 32 days. Analytic and Monte Carlo computations have been used to predict physical quantities useful in treatment planning and radiation protection. Analytic calculations based on the primary photon spectrum of 169Yb (excluding energies less than 10 keV) yield an air-kerma rate constant of 0.0427 cGy cm2 h-1 MBq-1, and an exposure rate constant of 1.80 R cm2 mCi-1 h-1 for this radionuclide. Calculated fmed factors are 0.922 cGy/R for soft tissue and 2.12 cGy/R for bone. The first half-value layer in lead is 0.2 mm; the first tenth-value layer is 1.6 mm. Using Monte Carlo simulations, the relative dose distributions around 169Yb seeds (Amersham, prototypes 4 and 5) are provided, and are then compared with those around an 125I seed (3M model 6702). The 169Yb seeds produce more isotropic dose distributions, and for permanent implants, can deliver it at a greater initial dose rate. A value of 1.19 cm-2 was also calculated for the specific dose constant D0, a value which is applicable to both seed types. Radiation protection is not as easily achieved for permanent implants with 169Yb because of the higher energy emissions (vs 125I). However, for temporary implants, Ytterbium-169 may prove to be a useful substitute for 192Ir or 137Cs because of its relatively lower energy emissions. It is concluded that 169Yb merits further investigation, including dosimetry, radiobiological, and clinical studies.


[Endoscopic implantation of balloon expandable endoprostheses (Strecker stents) in extrahepatic bile duct stenoses].

22 balloon expandable wire Strecker-stents were implanted endoscopically in 20 patients (eleven women, nine men, mean age 68.3 [44 to 86] years) with malignant (n = 19) and benign (n = 1) bile duct obstruction. In all cases an effective biliary drainage was obtained. To achieve complete drainage repeated balloon dilatation of the inserted stent was often performed. In two cases stent dislocation occurred immediately after implantation. Additional complications were not observed during the first 30 days. During the observation period of maximally 15 months one patient developed an incomplete occlusion of the stent due to tumor compression that could be reversed endoscopically. In a further patient biliary stones caused relapse of cholestatic jaundice. Four patients died from their malignant disease without evidence of stent occlusion. 15 patients continue to live without renewed jaundice. With the mean observation period of 5.5 months (median five months) this corresponds to a patency rate of 95%. The estimated survival rate according to Kaplan-Meier was 87.7% and the estimated mean survival time 11.7 months. These results demonstrate that in patients with extrahepatic bile duct obstruction an effective biliary drainage can be achieved with balloon expandable wire stents. They represent a further progress in the palliative treatment of patients with extrahepatic obstructive jaundice.


Neutron capture therapy with 235U seeds.

A combination of brachytherapy and neutron capture therapy has been evaluated using 235U metal seeds and external neutron beam irradiation. When thermal neutrons are absorbed by 235U, high-energy neutrons and gamma rays are produced and some of these deposit energy in surrounding tissue. A Monte Carlo program, using the code MCNP, has been used to evaluate two sizes of 235U seeds in a water phantom. The results of flux suppression around the seeds and dose distributions are illustrated and discussed. The results show that high doses can be delivered in a relatively short time by using 235U seeds with neutron capture therapy. This therapy with multiple needles or seeds can be envisioned as a substitute for traditional brachytherapy to give an effective killing dose.


Volume-based geometric modeling for radiation transport calculations.

Accurate theoretical characterization of radiation fields is a valuable tool in the design of complex systems, such as linac heads and intracavitary applicators, and for generation of basic dose calculation data that is inaccessible to experimental measurement. Both Monte Carlo and deterministic solutions to such problems require a system for accurately modeling complex 3-D geometries that supports ray tracing, point and segment classification, and 2-D graphical representation. Previous combinatorial approaches to solid modeling, which involve describing complex structures as set-theoretic combinations of simple objects, are limited in their ease of use and place unrealistic constraints on the geometric relations between objects such as excluding common boundaries. A new approach to volume-based solid modeling has been developed which is based upon topologically consistent definitions of boundary, interior, and exterior of a region. From these definitions, FORTRAN union, intersection, and difference routines have been developed that allow involuted and deeply nested structures to be described as set-theoretic combinations of ellipsoids, elliptic cylinders, prisms, cones, and planes that accommodate shared boundaries. Line segments between adjacent intersections on a trajectory are assigned to the appropriate region by a novel sorting algorithm that generalizes upon Siddon's approach. Two 2-D graphic display tools are developed to help the debugging of a given geometric model. In this paper, the mathematical basis of our system is described, it is contrasted to other approaches, and examples are discussed.


Gadolinium as a neutron capture therapy agent.

The clinical results of treating brain tumors with boron neutron capture therapy are very encouraging. Researchers around the world are once again making efforts to develop this therapeutic modality. Gadolinium-157 is one of the nuclides that holds interesting properties of being a neutron capture therapy agent. It is estimated that tumor concentrations of up to 300 micrograms 157 Gd/g tumor can be achieved in brain tumors with some MRI contrast agents such as Gd-DTPA and Gd-DOTA, and up to 800 micrograms 157 Gd/g tumor can be established in bone tumors with Gd-EDTMP. Monte Carlo calculations indicate that with 250 ppm of 157Gd in tumor, neutron capture therapy can deliver 2000 cGy to a tumor of 2-cm diameter or larger with 5 x 10(12) n/cm2 of thermal neutron fluence at the tumor. Dose measurements with films and TLDs in phantoms verified these calculations. More extended Monte Carlo calculations demonstrate that neutron capture therapy with Gd possesses comparable dose distribution to B neutron capture therapy. With 5 x 10(12) n/cm2 thermal neutrons at the tumor, Auger electrons from the Gd produced an optical density enhancement on films that is similar to the effect caused by about 300 cGy of Gd prompt gamma dose and may further enhance the therapeutic effects.


Macroscopic geometric heterogeneity effects in radiation dose distribution analysis for boron neutron capture therapy.

Calculations of radiation flux and dose distributions for boron neutron capture therapy (BNCT) of brain tumors are typically performed using sophisticated three-dimensional analytical models based on either a homogeneous approximation or a simplified few-region approximation to the actual highly heterogeneous geometry of the irradiation volume. Such models should be validated by comparison with calculations using detailed models in which all significant macroscopic tissue heterogeneities and geometric structures are explicitly represented as faithfully as possible. This paper describes such a validation exercise for BNCT of canine brain tumors. Geometric measurements of the canine anatomical structures of interest for this work were performed by dissecting and examining two essentially identical Labrador retriever heads. Chemical analyses of various tissue samples taken during the dissections were conducted to obtain measurements of elemental compositions for the tissues of interest. The resulting geometry and tissue composition data were then used to construct a detailed heterogeneous calculational model of the Labrador head. Calculations of three-dimensional radiation flux distributions pertinent to BNCT were performed for this model using the TORT discrete-ordinates radiation transport code. The calculations were repeated for a corresponding volume-weighted homogeneous-tissue model. Comparison of the results showed that peak neutron and photon flux magnitudes were quite similar for the two models (within 5%), but that the spatial flux profiles were shifted in the heterogeneous model such that the fluxes in some locations away from the peak differed from the corresponding fluxes in the homogeneous model by as much as 10%-20%. Differences of this magnitude can be therapeutically significant, emphasizing the need for proper validation of simplified treatment planning models.


[The anatomical characteristics of the root furcations in the molar teeth].

The aim of the present study has been to realize a morphometrical and morphological study on the anatomical characteristics of molar teeth root furcations. Two hundred ninety four molars (147 upper and 147 lower teeth), after extraction and elimination of periodontal ligament residuals by trypsin, have been morphometrically evaluated recording the principal anatomical characters of the furcal and radicular region (root and radicular trunk lengths, mesio-distal and vestibulo-palatal diameters at the cementum-enamel junction, inter-radicular angle width and furcal area extension). By the Pearson's correlation test data such obtained were analyzed to verify the existence of statistically significant correlations among the above mentioned anatomical characteristics. Thirty teeth, selected among the most representatives of the whole sample for their anatomical characters, have been morphologically evaluated: 10 by stereo-microscopical examination, 10 by the observation of non-demineralized histological sections and 10 by scanning electron microscopical examination. Results of the morphometrical evaluation showed that from first to second molar the radicular angle, root length and furcal area width undergo a reduction; differently radicular trunk increases his length. On the basis of this results the Authors try to explain data from recent clinical research testifying that second upper molar is the most frequently extracted tooth. In fact a long radicular trunk is associated with a more apical placement of the furcation entrance and this situation, in conjunction with a narrow inter-radicular angle, can obstruct the insertion of therapeutical instruments, justifying the bad prognosis of the second upper molar involved by periodontal disease. The statistical analysis of anatomical data showed a significant correlation (r = -0.46) among radicular trunk length and inter-radicular angle width (in upper first molars; reverse correlation), root length and inter-radicular angle width (r = 0.51) (lower first molars), vestibular-buccal diameter at the cementum-enamel junction and width of mesial and distal furcal angles (r = 0.43) (upper second molars), the extension of furcal area and the wideness of inter-radicular angle (r = 0.89/0.43). These data are in accord with those from other Authors. Morphological analysis showed the high structural complexity of furcal area in molar teeth with the common observation of cemental crests and pulpal accessory canals orifices; these structures can offer a good receptacle to the subgingival dental plaque and can cause difficulties in debridement and therapeutical treatment of the molar furcal region involved by periodontal disease.(ABSTRACT TRUNCATED AT 400 WORDS)


[The orodental findings in the Ehlers-Danlos syndrome. A report of 2 clinical cases].

Ehlers-Danlos syndrome (EDs) is a hereditary disorder of the connective tissue. Its clinical expression is variable and there are many difficulties in recognizing the disease because of the presence of eleven different forms. In this study the authors describe the oral manifestations in two cases of EDs. The children show hyperelasticity of the skin, easy bruisability, hyperextensibility of the joints, several dental manifestations: periodontitis, many caries, supernumerary teeth or hypodontia.


[Preliminary research on the prognosis of late reimplants with prior conditioning with a fluoridated solution].

The principal factors that affect the prognosis of a posttraumatic reimplantation are the length of the extra-alveolar persistence and the manner in which the extracted tooth is preserved. Both are fundamental for the maintenance of the fiber vitality of the periodontal ligament. The necrosis of these fibers cause ankylosis. It is observed that the conditioning of the radicular surface with fluoride solutions before the reimplantation is likely to slow down the evolution of radicular resorption. To evaluate the effectiveness of such methodology six cases of traumatic extractions, characterized by a length of extra-alveolar persistency (not longer than 24 hours), and unfavorable conditions of the preserved tooth have been treated by conditioning the radicular surface with the Na-fluoride solution before the reimplantation. Another group of reimplantation cases with the same characteristics have been examined without proceeding first to the radicular conditioning. The results of the study, although preliminary, verified the positive influence of the Na fluoride upon the radicular resorption.


[Neuromuscular assessment and postural examination in patients with TMJ condylo-meniscal incoordination].

The neuromuscular system plays a primary role in the development of a myofascial syndrome of the temporomandibular joint. Patients suffering from this disease very often show changes in muscular functions. In biomechanical clinical pictures of temporomandibular myofascial syndrome the motor apparatus is involved only in the second stage. In order to determine the efficiency of the motor apparatus and to schedule a physiotherapeutic treatment program to improve condylar-meniscus coordination of the joint, an analysis of muscular function associated with postural examination has been performed, and this with a view to evidence possible skeletal changes, with particular regard to the spine. The study has been carried out in a group of healthy individuals in front of an other group of patients affected by the pathology mentioned.


[The influence of the "age factor" on periodontal conditions in the diabetic patient].

Conflicting reports exist in dental literature on the relationship of diabetes mellitus to periodontal disease. Among the controversies about this relation, the role played by the age of patient has been widely investigated. Some authors, in fact, reported an increased prevalence and severity of gingivitis and periodontitis in children and young individuals with insulin dependent diabetes mellitus (IDDM) in comparison to healthy subjects, while other researchers were not able to confirm this finding. In particular some authors postulated the hypothesis that the diabetic state could influence periodontal conditions just after the age of 30-35. The aim of the present study has been to verify this hypothesis. One hundred thirty-two subjects participated in this study; among them 66 were IDDM patients and 66 were healthy controls comparable to the diabetics for the main epidemiological features. In particular, control subjects were similar to the diabetics for oral hygiene level in order not to attribute eventually occurring differences by mistake to the diabetic state instead of to a not comparable amount of bacterial plaque present on the teeth. Among 66 IDDM patients 33 were younger than 30 (medium age = 14; extremes: 6-22) and were indicated as DG (young diabetics) group; others 33 were older than 30 (medium age = 45.1; extremes: 31-66) and were indicated as DA (adult diabetics) group. A similar differentiation was made in the control group obtaining, in this way, two subgroups (CG = young controls and CA = adult controls). In the diabetic groups males were 53% while among controls they represented 58%.(ABSTRACT TRUNCATED AT 250 WORDS)


[Flurbiprofen in oral surgery].

Odontic surgery necessitates the very frequent use of additional auxiliary therapy to improve the post-operative symptoms. In fact the injured tissues respond to such surgical operations generally with an infiltrative-type process which is manifested predominantly by pain, pyrexia, oedema and in the more serious cases with total functional incapacity. The therapy for such symptomatology usually consists of NSAID, steroidal anti-inflammatories and/or chemotherapy. The scope of this research was to verify the possibility of utilising, exclusively, a potent non steroidal antiinflammatory whilst evaluating its therapeutic effects on the pain, the pyrexia and the oedema sustained following odontic surgery. The drug under examination was flurbiprofen, a medication with powerful antiinflammatory, analgesic and antipyretic properties whose mode of action, typical of this type of drug, is principally explained by its inhibition of prostaglandins biosynthesis. Moreover, flurbiprofen has been shown to be a potent inhibitor of platelet aggregation and of the migration of leucocytes. It has other pharmacological mechanisms of action but so far these remain insufficiently well explained. For the above mentioned study, 50 patients who had consented to take part were to undergo odontic surgery near to our clinic. They were subdivided into two groups, each consisting of 25 subjects, and each group was assigned an exclusive therapeutic regimen based on flurbiprofen. Patients in the first group were administered a flurbiprofen dose of 300 mg/day, by mouth, commencing on the day preceding the surgery and then on the next 7 consecutive days.(ABSTRACT TRUNCATED AT 250 WORDS)


Preliminary report: medical examiner reports of deaths associated with Hurricane Andrew--Florida, August 1992.

On August 24, 1992, at 1:40 a.m. eastern daylight time (EDT), rain bands associated with Hurricane Andrew reached the eastern coast of Florida. At 4:45 a.m. EDT, Hurricane Andrew made landfall 35 miles southeast of Miami at Homestead, with sustained winds of 145 miles per hour (mph) and gusts of 164 mph. These winds extended 45 miles outward of the storm center. The storm moved across the state at 18 mph toward the Gulf of Mexico (Figure 1). The tidal surge on the eastern coast was estimated at 7-19 feet. During the storm, approximately 2.5 million Florida residents were left without electrical power, and approximately 56,000 family dwelling units were destroyed or severely damaged. This report presents preliminary data from Florida medical examiner (ME) offices about deaths attributed to Hurricane Andrew.


Syphilis--Ford County, Kansas, 1992.

In January 1992, the Ford County (Kansas) Health Department received a report of a pregnant women with a positive serologic test for syphilis. Syphilis had not been reported in the county (1990 population: 27,463) since September 1989. As a result of the investigation summarized in this report, six additional persons with syphilis were identified by contact tracing.


Public health focus: effectiveness of smoking-control strategies--United States.

In 1990, approximately 46 million adults in the United States continued to smoke; however, more than 44 million persons were former smokers (1) who had reduced their risk for the leading causes of death in the United States (2). Smoking-cessation methods can be categorized as 1) self-help strategies (e.g., quitting abruptly and completely ["cold turkey"], using quitting manuals, or using nonprescription drugs) or 2) assisted strategies (e.g., smoking-cessation clinics, hypnosis, acupuncture, or nicotine gum or patch with counseling). This report summarizes information regarding the efficacy and cost-effectiveness of smoking-cessation strategies.


Reporting of race and ethnicity in the National Notifiable Diseases Surveillance System, 1990.

Since 1989, all state health departments have reported cases of infectious diseases to the National Notifiable Diseases Surveillance System (NNDSS) through the National Electronic Telecommunications System for Surveillance (NETSS) (1). Electronic reporting allows reporting of additional information, including demographic data, that can be used to help define the scope of public health problems for different groups and to develop appropriate preventive interventions. This report describes reporting through NNDSS of notifiable diseases by patients' race/ethnicity for 1990.


[An experimental study on the rejection phenomenon of multi-visceral allografts in pigs].

Multi-visceral allografts including the liver, pancreas and gastrointestinal tract were transplanted in 10 pigs. Eight of them survived for 7 to 21 days. Histopathological changes were studied in the liver, pancreas and gastrointestinal tract. An en bloc transplantation revealed no particular course after transplantation than those individual organ transplantation. The status of rejection was assessed by our histological criteria, which are divided into 5 grades about the liver and 4 grades about other organs according to the severity of the acute rejection. A higher grade of rejection was apparently in the small and large intestine especially after the 10th post-transplanted day (Grade II to III in the small and large intestine v. Grade 0 to II in the liver, stomach and pancreas). The study suggests the existence of organ specific susceptibility to rejection in multi-visceral organ transplantation.


[Experimental study for lymphatic routes of the cardia and diaphragm].

We report discovery of the lymphatic routes in the gastric cardia and adjacent diaphragm after producing a blockage in the descending lymphatic route in dogs. CH40 black carbon hydrate was injected into the cardia portion during operation followed by total gastric and diaphragm combined resection to investigate lymphatic routes. In the 12 dogs with a blockage, and an ascending route to the lower mediastinum was recognized in 4 cases, and lateral routes from the hiatus of the esophagus to the diaphragm in a further 3 of the 12 cases. The lateral route was considered to be a collateral lymphatic route of neo-lymphatic vessel. Further, we found that phrenic lymphatic flows went in multiple directions, whereas the lymphatic flow at the phrenic lumbar vertebrae went mainly in the direction of the esophageal opening or aortic opening, although there was some expansion to the mediastinal side or celiac side. Consequently, it was assumed that metastasis to the lateral direction besides the ascending route might occur in cases with cancer in the cardiac portion infiltrating to the hiatus of the esophagus.


[Clinicopathological and immunohistochemical studies on carcinoma of the papilla of Vater].

The non-invasive adenomatous component (nac) was observed in 44% of 32 resected specimens of carcinoma of the papilla of Vater. Incidence of the "nac" positive carcinoma declined with cancer staging, but there was no significant relationship between the "nac" and tumor size. The "nac" positive rates in "tumor forming", "ulcerating" and "mixed" types were 65, 0 and 38%, respectively. The "nac" negative carcinoma metastasized more frequently to the lymph nodes, duodenum, pancreas and veins. The five year survival rates of the patients with the "nac" positive and negative carcinoma were 78 and 22%, respectively. Immunohistochemically, the "nac" positive carcinoma mostly showed partial distribution of CA19-9, while the "nac" negative carcinoma, carcinoma of the pancreas and bile duct mostly showed diffuse distribution. The intact mucosa of the common channel and orifice of the papilla almost showed partial distribution, and duodenal mucosa showed negative distribution. The pancreatic and bile duct almost indicated diffuse distribution. The "nac" may be precancerous condition and the "nac" positive carcinoma may arise from the common channel or the orifice of the papilla or the duodenum. But the "nac" negative carcinoma may belong primarily to carcinoma of the pancreas and bile duct as de-novo carcinoma.


[Mitochondrial energy synthesis during cold preservation and after reperfusion in liver transplantation].

In liver transplantation, primary graft nonfunction (PGN) occurred 5 to 10% in all cases. For preventing PGN it is necessary to elucidate a reliable assessment procedure for graft function before transplantation. In addition, methods of harvest or preservation which can maintain good viability of the graft are also needed. The purpose of this study is to clarify whether mitochondrial respiratory ratio (RCR), which is ability of ATP synthesis, is a reliable marker of the graft viability and whether a harvesting method with an artificial heart and lung is effective for keeping high energy synthesis of mitochondria or not. Pigs were used for this study. In a standard harvest method RCR decreased gradually during cold preservation. Grafts with values of RCR more than 3.0 had good function after transplantation. RCR depended on mitochondrial ATP, not tissue ATP. Grafts harvested with artificial heart and lung kept RCR more than 4.0 at 12 hours after preservation. Five of 6 pigs transplanted 12 hours preserved liver harvested from the donor with an artificial heart and lung survived more than 5 days. These results suggested that mitochondrial ATP synthesis has strong relation to PGN and RCR is a reliable marker for graft viability.


[Effects of preoperative transcatheter portal embolization (TPE) on prevention of hepatic failure after massive hepatectomy].

Effects of TPE on prevention of hepatic failure after massive hepatectomy were studied experimentally using dogs. A 70% or 85% hepatectomy (Hx) was performed two weeks after TPE. All of the 70%Hx groups with(+)/without(-) TPE were alive for over two weeks after hepatectomy. While all of the 85%Hx group without TPE died, eight of ten in the 85%Hx group with TPE survived. Without TPE, total bilirubin levels in sera were elevated markedly in the 85%Hx group and moderately in the 70%Hx group after hepatectomy. The levels of escaped enzymes in sera, such as GOT or GPT, were also elevated remarkably in the TPE(-) groups. Although the levels of these enzymes were also high in the 85%Hx.TPE(+) group, these values were as same as those of 70%Hx.TPE(-) group. In the 85%Hx.TPE(-) group, critical diminution of functional hepatic cell mass and severe portal hypertension occurred after hepatectomy and coagulopathy and death followed to these phenomena. TPE might prevent the onset of these critical phenomena, and diminish the damage caused by massive hepatectomy. These results suggest that TPE is useful for prevention of postoperative hepatic failure so that we could perform massive hepatectomy safely, and extend the operative indication.


[An experimental study on development of gallstone disease after curative gastrectomy for cancer--postoperative alteration of the composition of canine gallbladder bile after subtotal gastrectomy with truncal vagotomy].

In connection with gallstone (GS) formation after gastrectomy for cancer, we examined alteration of the composition of gallbladder bile after subtotal gastrectomy with truncal vagotomy. Of 11 mongrel dogs with cholecystostomy, 3 underwent B-I and 4 B-II gastrectomy. Four dogs without gastrectomy were served as controls. Bile was collected for 12 months. Bile acids were quantified by GLC. The bile was cultured for bacteriology. TBA did not significantly differ among the three groups of the dogs. In the two gastrectomized groups, CDA (a secondary bile acid) kept a higher level and CA (a primary bile acid) maintained a lower concentration compared with those in the controls. A remarkable increase of non-conjugated bile acids was recognized in both gastrectomized groups. Lithogenicity was low for all of the 3 groups. All but 1 control dog incurred bile infection that persisted long. Black pigment stones containing calcium bilirubinate developed in 1 of the 3 B-I and 2 of the 4 B-II dogs but none in the controls. The bile infection seemed to be involved in the development of GS. As the alteration of bile composition and GS occurred solely in the gastrectomized dogs, subtotal gastrectomy with truncal vagotomy might precipitate the GS formation.


[The effect of portal venous drainage on graft survival and function in rat whole pancreaticoduodenal transplantation].

A whole pancreaticoduodenal transplant model with portal venous drainage was achieved in the rat, and effect of venous drainage from pancreas grafts into the portal vein on the functional graft survival and long-term glucose metabolism was investigated. In allogeneic series between ACI (RT1a) donors and streptozotocin-induced diabetic Lewis (RT1l) recipients (nonfasting plasma glucose greater than or equal to 400 mg/dl), the mean survival time of pancreas transplants determined by recurrent hyperglycemia (greater than or equal to 200 mg/gl) in rats with portal venous drainage (PV-group: 8.9 +/- 1.3 days) was slightly longer than that in rats with systemic venous drainage (SV-group: 8.3 +/- 0.9 days), but statistically insignificant. In the syngeneic series using Lewis rats, K-values (%/min) in IV-GTT at 1, 2 and 3 months after pancreas transplantation were, respectively, 1.5 +/- 1.0, 2.0 +/- 0.6 and 2.3 +/- 0.7 in PV-group, and 1.2 +/- 0.3, 1.2 +/- 0.4 and 1.8 +/- 0.5 in SV-group. Peripheral IRI (microU/ml) levels before glucose load were higher in both groups (PV-group, 15.1 +/- 10.5: SV-group, 22.8 +/- 16.2) at 3 months than in normal control (7.9 +/- 1.6: p greater than 0.05). These results indicate that the portal venous drainage in pancreas transplants has no remarkable profit in graft survival and that it can provide more physiological glucose control but cannot normalize insulin concentration.


[Does L-thyroxine administration in a dose to suppress TSH secretion induce metabolic bone disturbance in patients with thyroid carcinoma?].

We investigated whether L-thyroxine for TSH suppression may induce metabolic bone disturbance, especially in trabecular bone. Subjects were 75 premenopausal women (mean age: 37.7) who underwent surgery at Ito Hospital or Yokohama City University Hospital from 1972 to 1988 for differentiated thyroid carcinoma. All of them received L-thyroxine for the purpose of TSH suppression. According to the duration of the drug therapy after surgery, they were divided into 3 groups: Group I patients were treated for more than 10 years after surgery (17 cases), Group II from 5 to 10 years (28 cases), and Group III less than 5 years (30 cases). The control group was consisted of 15 premenopausal women (mean age: 37.0). There was no significant difference in age among these 4 groups. Quantitative CT was used for evaluation of trabecular bone mineral content. Mean bone mineral contents determined in Group I, Group III, Group II and control group patients were 204.7, 213.1, 207.6, 222.6 mg/cm3, respectively. There was no significant difference among them. It is concluded that L-thyroxine can be administered safely without metabolic disturbance in trabecular bone.


[An immunological study of changes in the thymus with aging].

Immunological changes of the thymus with aging were studied in human thymic lymphocytes that were obtained from 48 patients undergoing open heart surgery at the 2nd Department of Surgery, Tottori University Hospital. Flow cytometric analysis indicated significant reductions in the ratios of CD8, CD4, and CD1 positive thymic lymphocytes with aging significant increases in the ratios of HLA-DR and CD20 positive cells, and no significant change in the ratio of CD3 positive cells. Immunohistological staining indicated a predominance of CD8, CD4, and CD1 positive cells in the cortex of the thymus, while a predominance of CD3, HLA-DR, and CD20 positive cells was indicated in the medulla of the thymus. The mitogen responses of thymic lymphocytes to PHA, Con A, and PWM were enhanced with aging. Quantitative analysis of the subsets of thymic lymphocytes, their distribution in the thymus, and the measurement of the mitogen responsiveness of those lymphocytes are indispensable for obtaining basic data indicating immunological changes of the thymus with aging, as well as for clarifying the age-related characteristics of thymic lymphocytes in cases of autoimmune diseases such as myasthenia gravis.


[Surgical treatment of chronic intestinal ischemia associated with combined valvular disease].

A 69-year-old male was admitted with congestive heart failure and postprandial abdominal pain with weight loss. Combined valvular disease (MR III+TR III) was demonstrated by cardiac catheterization. Selective visceral arteriography revealed 75% stenosis at the origin of SMA and common hepatic artery arose beyond the stenosis. SMA-abdominal aortic bypass grafting using auto-saphenous vein graft was performed initially. Postprandial abdominal pain disappeared after bypass grafting, and then MVR with Björk-Shiley mechanical valve and TAP with Carpentier- Edwards ring was performed.


Genetic and molecular evidence for a trans-acting regulatory locus controlling glutathione S-transferase-2 expression in Aedes aegypti.

The amount of glutathione S-transferase-2 (GST-2) protein and enzyme activity in a mutant strain (strain GG) of the yellow fever mosquito (Aedes aegypti) is approximately 25-fold higher than in the wild-type (++) strain. The mode of inheritance of the GG phenotype was studied in F1 and backcross progeny using GST enzyme assays, isozyme-specific antisera, and Northern blot analysis. Enzyme assay of parental and F1 progeny showed that the ++ phenotype was dominant to the GG phenotype. This was true for larvae as well as for all tissues examined in adults in both sexes. Immunoblotting experiments showed that, like the ++ strain, F1 larvae and adults express very low levels of GST-2 protein compared with the GG strain. Northern blotting experiments showed that the steady-state levels of GST-2 mRNA in parental and F1 hybrid larvae closely matched the enzyme activity and immunological data. These results suggest the existence of a trans-acting regulatory locus that acts to repress GST-2 mRNA transcription and/or decrease GST-2 mRNA stability in ++ and F1 hybrids. GST enzyme activity in backcross progeny, however, did not segregate into the two distinct phenotypes (low and high) predicted for a single locus, dominant allele model. Backcross progeny expressed a wide range of GST activity and GST-2 protein amount with no apparent fit to simple Mendelian ratios. These backcross data suggest that additional loci are also involved in regulating GST-2 isozyme expression.(ABSTRACT TRUNCATED AT 250 WORDS)


Use of the polymerase chain reaction to isolate an S-locus glycoprotein cDNA introgressed from Brassica campestris into B. napus ssp. oleifera.

A self-incompatible canola-quality Brassica napus ssp. oleifera line (W1) was generated by introgressing the S-locus from a self-incompatible B. campestris plant into the Westar cultivar. Using the polymerase chain reaction (PCR) with primers derived from conserved regions in S-locus glycoprotein (SLG) alleles, the central region of the active SLG gene (910) was obtained. The remaining portions of the cDNA for this 910 gene were subsequently cloned using the PCR-rapid amplification of cDNA ends (RACE) procedure. Sequence analysis revealed that the 910 cDNA show a high degree of sequence similarity to SLG alleles associated with Class I self-incompatible lines. The 910 gene was found to be absent in the original self-compatible cv. Westar (B. napus) and segregated with self-incompatibility in a mixed population generated from a cross between self-incompatible W1 and self-compatible Westar. RNA blot analysis indicated that high levels of 910 mRNAs were present in the stigma as buds approached anthesis. Thus, the SLG allele of W1 transferred from B. campestris via backcrosses to a line of cv. Westar has been identified.


ore2, a mutation affecting proline biosynthesis in the yeast Saccharomyces cerevisiae, leads to a cdc phenotype.

We report here the isolation of temperature-sensitive mutants of the yeast Saccharomyces cerevisiae which exhibit cdc phenotypes. The recessive mutations defined four complementation groups, named ore1, ore2, ore3 and ore4. At the non-permissive temperature, strains bearing these mutations arrested in the G1 phase of the cell cycle. The wild-type allele of the gene altered in ore2 mutants was cloned. The nucleotide sequence of a fragment which can complement the mutation showed the presence of an open reading frame capable of encoding a protein with 286 amino acid residues. The deduced amino acid sequence showed 25% identity with that of the Escherichia coli delta 1-pyrroline-5-carboxylate reductase, an enzyme of the pathway for the biosynthesis of proline. The ore2 mutants, correspondingly, were found to be capable of growing at the non-permissive temperature on a synthetic medium supplemented with proline. In addition, the chromosomal location of the gene and its restriction map were compatible with those previously reported for the PRO3 gene which encodes the S. cerevisiae delta 1-pyrroline-5-carboxylate reductase.


Stress response induced by DNA damage leads to specific, delayed and untargeted mutations.

Cells of the mouse T-lymphoma line GRSL13 were treated with 8-methoxy-psoralen plus longwave ultraviolet light (PUVA) under conditions where the biological effects are mainly due to non-persistent DNA cross-links (PUVA-CL treatment). Fluctuation analysis showed that PUVA-CL treatment resulted in an enhancement of the mutation rate in the progeny of treated cells, which persisted until the eleventh generation after treatment. Since only 5 cross-links are available to account for 52 mutational events observed in the coding region, about 90% of the induced mutational events must have been untargeted. This was confirmed by molecular analysis of these mutations, which showed that 53% of the point mutations arose at sites which are not a target for psoralens. This supports the hypothesis that stress responses may give rise to untargeted mutagenesis. Further support for this hypothesis is provided by the observation that 8-methoxy-psoralen (8-MOP) or UVA alone (both of which are known to induce many pleiotropic effects) each acted as indirect mutagen by enhancing the mutation rate 2-4 fold in the progeny of treated cells.


Structure and regulation of yeast HEM3, the gene for porphobilinogen deaminase.

Porphobilinogen deaminase is the third enzyme in the heme biosynthetic pathway. hem3 mutants in Saccharomyces cerevisiae are deficient in porphobilinogen deaminase activity. We have isolated the HEM3 gene by complementation of the heme auxotrophy of a hem3 mutant. Sequence analysis reveals an open reading frame of 981 nucleotides. The derived amino acid sequence of the protein encoded by HEM3 shows extensive homology to the reported sequences for porphobilinogen deaminase from a number of other sources, indicating that HEM3 is the structural gene for porphobilinogen deaminase. Earlier reports have suggested that expression of HEM3 is induced by porphobilinogen, the substrate of the encoded enzyme. We have investigated the transcription of HEM3 and have found that it is not affected by the ability of the cell to make porphobilinogen or heme. However, we have found that HAP2 and HAP3 gene products are involved in the expression of HEM3. An important element required for expression of HEM3 has been localized to a small region that contains a sequence homologous to the HAP2-3-4 binding sites of several genes including HEM1. These findings suggest that HEM3 expression is regulated in the same manner as that of HEM1 which encodes the first enzyme of the heme biosynthetic pathway.


Molecular characterization of two types of 22 kilodalton alpha-zein genes in a gene cluster in maize.

Five genes of the alpha-zein subfamily four (SF4) are located in a 56 kb genomic region of the maize inbred line W22. Their nucleotide and deduced amino acid sequences have been determined. The sequences define two types of alpha-zein SF4 genes-type 1 (T1) and type 2 (T2). The single T1 alpha-zein SF4 gene codes for an alpha-zein protein with a M(r) of about 22,000. This is the first alpha-zein SF4 gene sequenced that contains no early in-frame stop codons in its coding sequence. The four T2 alpha-zein SF4 genes in this cluster contain one or two early in-frame stop codons. In addition, our T1 and T2 genes differ markedly in the base sequences of their distal 5' non-translated flanking regions. The nucleotide and the deduced amino acid sequences of these two types of alpha-zein SF4 genes are similar (greater than 90%) to one another and to all known alpha-zein SF4 genes and cDNAs. Of the known W22 alpha-zein SF4 genes, only one in six does not contain an early in-frame stop codon. If the number of alpha-zein SF4 genes is 15-20, then we estimate that only about 4 of the W22 alpha-zein SF4 genes are without in-frame early stop codons.