Position specificity in the genus Coreomyces (Laboulbeniomycetes, Ascomycota).

To study position specificity in the insect-parasitic fungal genus Coreomyces (Laboulbeniaceae, Laboulbeniales), we sampled corixid hosts (Corixidae, Heteroptera) in southern Scandinavia. We detected Coreomyces thalli in five different positions on the hosts. Thalli from the various positions grouped in four distinct clusters in the resulting gene trees, distinctly so in the ITS and LSU of the nuclear ribosomal DNA, less so in the SSU of the nuclear ribosomal DNA and the mitochondrial ribosomal DNA. Thalli from the left side of abdomen grouped in a single cluster, and so did thalli from the ventral right side. Thalli in the mid-ventral position turned out to be a mix of three clades, while thalli growing dorsally grouped with thalli from the left and right abdominal clades. The mid-ventral and dorsal positions were found in male hosts only. The position on the left hemelytron was shared by members from two sister clades. Statistical analyses demonstrate a significant positive correlation between clade and position on the host, but also a weak correlation between host sex and clade membership. These results indicate that sex-of-host specificity may be a non-existent extreme in a continuum, where instead weak pREFERENCES for one host sex may turn out to be frequent.

Long-term effects of footshock and social defeat on anxiety-like behaviours in rats: relationships to pre-stressor plasma corticosterone concentration.

We compared the consequences of two stressors, 'unnatural' inescapable footshocks (IFSs) and 'natural' social defeat (SD), on behaviours typically sensitive to stress [sucrose preference, open field (OF), elevated plus maze (EPM) and acoustic startle responses (ASRs)] and the association with pre-stressor plasma corticosterone concentration. After initial blood sampling, rats (n = 20 per group) were exposed to either 10 IFSs (1 mA intensity, 5 s duration each) or to 1 h SD (defeat by an aggressive resident male rat and further exposure but separated in a small cage) or to control procedures (handling). Rats were tested once for ASR (day 19), while the other behavioural tests were applied once weekly for 3 weeks. Both stress groups showed short-lasting lowered sucrose preference, and in the EPM they showed shorter total distance moved, shorter distance moved on open arms and less time on open arms compared to controls. In the OF test, IFS rats showed shorter total distance moved up to 2 weeks after stress. The SD group showed shorter total distance moved in the OF, which was only significant 2 weeks after stress. Low pre-stressor plasma corticosterone concentration was only associated with defecation (IFS rats) and latency to enter open arms in the EPM (all low corticosterone subgroups, n = 10 per subgroup). SD rats with high initial plasma corticosterone concentration showed enhanced ASR compared to the other subgroups with high initial plasma corticosterone concentration (n = 9 per subgroup). The results indicate that footshock and SD, while generally leading to an increase in anxiety behaviours, represent qualitatively different stressors.

Soluble CD27 induces IgG production through activation of antigen-primed B cells.

OBJECTIVES: High levels of soluble CD27 (sCD27), a marker of immune activation, are found in several infectious [including human immunodeficiency virus type-I (HIV-1)] and autoimmune diseases; however, a direct biological effect of sCD27 on B cells has not been established. The aim of this study was to investigate whether sCD27, by binding to CD70, can induce immunoglobulin G (IgG) production from B cells. METHODS: B cells from healthy and HIV-1-infected individuals were cultured with recombinant human sCD27 (rhsCD27), and IgG production was measured. The role of rhsCD27 in inducing the expression of transcription factors involved in plasma cell differentiation was evaluated. Furthermore, we investigated the impact of different cytokines on the modulation of CD70 expression on B cells and the relationship between levels of IgG and sCD27 in serum from healthy and HIV-1-infected individuals. RESULTS: We demonstrated that rhsCD27 induced IgG production from antigen-primed (CD27+) B cells. This effect was mediated by rhsCD27 binding to CD70 on B cells leading to activation of Blimp-1 and XBP-1, transcription factors associated with plasma cell differentiation. We found a significant correlation between levels of serum sCD27 and IgG in HIV-1-infected individuals and healthy controls. CONCLUSIONS: sCD27 may act to enhance immunoglobulin production and differentiation of activated memory or recently antigen-experienced B cells, thus providing an activation signal to antigen-experienced B cells. This mechanism may operate during autoimmune and chronic infectious diseases, situations in which continuous immune activation leads to upregulation of CD70 expression and increased sCD27 cleavage.

Honig's model of working memory and brain activation: an fMRI study.

The present study investigated changes in neuronal activation with fMRI related to Honig's model of working memory, which is much less studied compared with other working memory models. In contrast to other studies which have applied recognition procedures, the primary aim with the present study was to examine brain activation when subjects had to continuously recall and forget items held in working memory. The results showed that the mid-ventrolateral frontal cortex was particularly activated in the left hemisphere, whereas the mid-dorsolateral frontal cortex was particularly activated in the right hemisphere during execution of the working memory task. The findings are discussed in relation to process- and domain-specific accounts of working memory.

A mouse knock-in model exposes sequential proteolytic pathways that regulate p27Kip1 in G1 and S phase.

The protein p27Kip1 is an inhibitor of cell division. An increase in p27 causes proliferating cells to exit from the cell cycle, and a decrease in p27 is necessary for quiescent cells to resume division. Abnormally low amounts of p27 are associated with pathological states of excessive cell proliferation, especially cancers. In normal and tumour cells, p27 is regulated primarily at the level of translation and protein turnover. Phosphorylation of p27 on threonine 187 (T187) by cyclin-dependent kinase 2 (Cdk2) is thought to initiate the major pathway for p27 proteolysis. To critically test the importance of this pathway in vivo, we replaced the murine p27 gene with one that encoded alanine instead of threonine at position 187 (p27T187A). Here we show that cells expressing p27T187A were unable to downregulate p27 during the S and G2 phases of the cell cycle, but that this had a surprisingly modest effect on cell proliferation both in vitro and in vivo. Our efforts to explain this unexpected result led to the discovery of a second proteolytic pathway for controlling p27, one that is activated by mitogens and degrades p27 exclusively during G1.

Different brain areas activated during imagery of painful and non-painful 'finger movements' in a subject with an amputated arm.

The purpose of the present study was to investigate differences in brain activation with functional magnetic resonance imaging (fMRI) during imagery of painful and non-painful 'finger movements' and 'hand positioning' in a subject with an amputated arm. The subject was a right-handed man in his mid-thirties who lost his right arm just above the elbow in a car-train accident. MRI was performed with a 1.5 T Siemens Vision Plus scanner. The basic design involved four conditions: imagining 'painful finger movements', 'non-painful finger movements', 'painful hand positioning', 'non-painful hand positioning'. Imagery of finger movements uniquely activated the contralateral primary motor cortex which contains the classic 'hand area'. The lateral part of the anterior cerebellar lobe was also activated during imagery of finger movements. Imagery of pain uniquely activated the somatosensory area, and areas in the left insula and bilaterally in the ventral posterior lateral nucleus of the thalamus. It is suggested that the insula and thalamus may involve neuronal pathways that are critical for mental processing of pain-related experiences, which may relate to a better understanding of the neurobiology of phantom limb pain.

Social inequality in oral health and use of dental care in Sweden.

OBJECTIVE: To describe oral health and use of dental care in relation to socio-economic determinants over time in Sweden. METHODS: Cross-sectional study based on interview data on two randomly sampled sequential populations consisting of 7,610 Swedish adult (25-64 years) residents and 4,315 children (3-15 years) in their households from the Survey of Living Conditions 1996-97, and 7,649 adult Swedish residents (25-64 years) from the survey of 1988-89. RESULTS: Low educational level, having no cash margin and being born outside of Sweden was associated with higher odds of problems with chewing, wearing a prosthesis and not having been treated by a dentist during the 24 months preceding the interview, in a logistic regression analysis of data from the 1996-97 survey in the adult study population (adjusted odds ratios 1.6-2.9). The same socio-economic determinants were associated with caries in children (adjusted odds ratios 1.2-1.5). The socio-economic differences in dental treatment and problems with chewing were greater in the age group 45-64 years compared to 25-44-year-olds. The prevalence of problems with chewing increased from 7.1% (95% CI 6.5-8.1) in the 1988-89 survey to 9.1% (8.4-9.8) in the 1996-97 survey. A similar increase, from 2.4% (2.2-2.6) to 4.4% (3.9-4.9) was observed for individuals not having been in dental treatment during the last 24 months. The socio-economic distribution of oral health and use of dental care in the adult population was similar in the two surveys. CONCLUSION: This study demonstrates that socio-economic differences in oral health and use of dental care are most marked in older (45-64 years) adults in Sweden, but are significant in young adults and, in terms of oral health, in children as well. A steep increase in user charges during the 1990s has been paralleled by a moderate increase in problems with chewing and the proportion of the population that has no regular dental care, which suggests a link that needs to be evaluated in further studies.

Restorative treatment decisions on occlusal caries in Scandinavia.

In order to map variations in the operative treatment threshold for occlusal caries, a pre-coded questionnaire was sent to a random sample of 759 dentists in Norway, 923 in Sweden, and 173 in the Danish Public Dental Health Service inquiring about caries and treatment strategies. A further intention was to explore the type of operative treatment and filling material dentists in Scandinavia would use given an occlusal lesion in the lower 2nd molar in a 20-year-old. It is found that close to 70% of dentists in the 3 countries would put off carrying out operative treatment of occlusal caries until they registered a moderately sized cavity and/or any radiolucency in dentin. In Sweden, 26.7% of dentists and in Denmark 24.3% would postpone operative treatment until the lesion had a large cavity and/or until radiolucency could be observed in the middle third of the dentin; in Norway, only 11.5% of dentists indicated this. The majority of dentists in all 3 countries preferred to drill only the carious part of the fissure, though in Norway more dentists (30.9%) would tend to drill the whole fissure compared to their Swedish (23.4%) and Danish (9.5%) colleagues. The majority of Danish dentists (52.4%) suggested amalgam for restoring the occlusal surface, while 19.9% of Norwegian and 2.9% of Swedish dentists would use amalgam. Composite was the first material of choice for 71.5% of the Swedish dentists, the remaining 25.6% suggesting conventional glass ionomer cement, light-cured 'glass ionomer cement', or a combination of glass ionomer cement and composite. The corresponding values for the Norwegian dentists were 39.1% and 41.0%, respectively, and for the Danish dentists 29.2% and 18.4%. In Scandinavia, the leading strategy for occlusal caries seems to be to postpone operative treatment until a definite cavity or radiolucency in the outer third of dentin can be observed, and to carry out operative treatment only of the part of the fissure that is carious. Composite resin is the predominant material of choice in Sweden, while in Denmark the majority of dentists preferred amalgam. Composite, or composite in combination with glass ionomer cement material, was the choice of almost 80% of Norwegian dentists.

A controlled study of oral self-care and self-perceived oral health in type 2 diabetic patients.

A controlled study was carried out in mid-Sweden with the aim of comparing oral self-care and self-perceived oral health in 102 randomly sampled type 2 diabetic patients with that of 102 age-and-gender-matched non-diabetic controls. Oral health variables were also related to glycemic control (HbA1c), duration, anti-diabetic treatment, and late complications. Questionnaires were used to collect data on oral self-care and self-perceived oral health. Diabetes-related variables were extracted from medical records. Eighty-five percent of the diabetic subjects had never received information about the relation between diabetes and oral health, and 83% were unaware of the link. Forty-eight percent believed that the dentist/ dental hygienist did not know of their having diabetes. Most individuals, but fewer in the diabetic group, were regular visitors to dental care and the majority felt unaffected when confronted with dental services. More than 90% in both groups brushed their teeth daily and more than half of those with natural teeth did proximal cleaning. Subjects in the diabetic group as well as in the control group were content with their teeth and mouth (83% vs 85%. Those with solely natural teeth and those with complete removable dentures expressed most satisfaction. Sensation of dry mouth was common among diabetic patients (54%) and subjects with hypertension exhibited dry mouth to a greater extent (65%) than those who were normotensive. Our principal conclusion is that efforts should be made to give information about diabetes as a risk factor for oral health from dental services to diabetic patients and diabetes staff.

Swedish dentists' decisions on preparation techniques and restorative materials.

This study aimed at mapping the preparation techniques and restorative materials that Swedish dentists are using for primary approximal and occlusal carious lesions. It involved sending a pre-coded questionnaire to a random sample of 923 dentists, with eight items concerning approximal and occlusal restorative preparation techniques and dental materials. Responses were received from 651 (70.5%) dentists. To restore a primary approximal carious lesion in an adolescent with low caries activity and good oral hygiene, the tunnel preparation was chosen by 48% of the dentists, the saucer-shaped preparation by 32%, and the traditional Class II preparation by 20%. The most common preparation technique for restoring an occlusal carious lesion was removal of the carious part only, which was chosen by 74% of the dentists. For a lower second molar with a minor occlusal caries lesion combined with a suspected dentin lesion as judged radiographically, about half of the dentists chose to restore the carious part only and 27% would seal the rest of the fissure system in addition. For a similar lesion with no obvious radiolucency in the dentin, about 1/3 chose the 'no treatment' alternative, 1/3 fluoride treatment, and the rest fissure sealing or other techniques. Composite was used most often and amalgam least often for both approximal and occlusal carious lesions.

Type 2 diabetes and oral health: a comparison between diabetic and non-diabetic subjects.

A controlled cross-sectional study with the aim of studying oral health in patients with type 2 diabetes was carried out in a health care district in Sweden. The study included 102 randomly sampled diabetic patients and 102 age- and gender-matched non-diabetic subjects from the same geographical area, treated at the same Public Dental Service clinics. Oral conditions were measured at clinical and X-ray examinations. Diabetes-related variables were extracted from medical records. Diabetic patients suffered from xerostomia (dry mouth) to a significantly higher degree than non-diabetic controls did (53.5 vs. 28.4%; P=0.0003). Sites with advanced periodontitis were more frequent in the diabetic group (P=0.006) as were initial caries lesions (P=0.02). Diabetic subjects showed a greater need of periodontal treatment (P=0.05), caries prevention (P=0.002) and prosthetic corrections (P=0.004). Diabetes duration or metabolic control of the disease was not related to periodontal status. However, patients with longer duration of diabetes had more manifest caries lesions (P=0.05) as had those on insulin treatment when compared with patients on oral/diet or combined treatment (P=0.0001). The conclusion is that individuals with type 2 diabetes in some oral conditions exhibited poorer health. Close collaboration between the patient, the primary health care and oral health professionals could be a way of improving the diabetic patient's general and oral health.

Functional magnetic resonance imaging (fMRI) study of sex differences in a mental rotation task.

The main purpose of the present study was to: 1) to investigate differences between males and females in brain activation when performing a mental rotation task, 2) investigate hemisphere differences in brain activation during mental rotation. Brain activation was measured with functional magnetic resonance imaging (fMRI). Image acquisition was performed with a 1.5 Tesla Siemens Vision MR scanner equipped with 25 m T/m gradients. Scanning of anatomy was done with a T1-weighted 3D FLASH pulse sequence. Serial imaging with 70 BOLD sensitive echo planar (EPI) whole brain measurements was done during stimulus presentations, divided into 7 blocks of 10 EPI multi-slice volume measurements each. Eleven subjects were presented with black-and-white drawings of 3-D shapes taken from the set of 3-D perspective drawings developed by Shepard and Metzler [1], alternated with 2-D white bars as control stimuli. In the experimental condition, the subjects were shown 36 pairs of 3-D drawings, presented in three blocks of 12 pairs of drawings. The drawings were always presented pairwise. On half of the trials, the two 3-D shapes were congruent but portrayed with different orientation, in the other half the two shapes were incongruent. MR data were analyzed with the SPM-96 analysis software. After subtraction of activity related to the 2-D control stimuli, clusters of significant activation were found in the superior parietal lobule (BA 7), more intensely over the right hemisphere, and bilaterally in the inferior frontal gyrus (BA 44/45). Males showed predominantly parietal activation, while the females showed inferior frontal activation. It is suggested that males and females may differ in the processing strategy used when approaching a 3-D mental rotation task, males using a 'gestalt' strategy and females using a 'serial' reasoning strategy.

Contribution of planar (0-1 ortho) and nonplanar (2-4 ortho) fractions of Aroclor 1260 to the induction of altered hepatic foci in female Sprague-Dawley rats.

The hepatic tumor promoting activity of the planar 0-1 ortho ( approximately 9.7% w/w) and the nonplanar 2-4 ortho ( approximately 90.3% w/w) fraction of the commercial PCB mixture Aroclor 1260 was studied using a medium-term two-stage initiation/promotion bioassay in female Sprague-Dawley rats. Fractionation was carried out on an activated charcoal column. The composition of the effluent from the column was tested by GC-ECD. The absence of planar compounds in the 2-4 ortho fraction was confirmed by GC-MS analysis. The dioxin-like toxic potency of the fractions was determined with the DR-CALUX assay. The animal experiment was started with the initiation procedure (diethylnitrosamine injection, 30 mg/kg body wt ip, 24 h after (2)/(3) hepatectomy), followed 6 weeks later by the promotion treatment, which consisted of a weekly subcutaneous injection during 20 weeks. Exposure groups (n = 10) received the following treatments (dose/kg body wt/week): Aroclor 1260 (10 mg), 0-1 ortho fraction (0.97 mg), 2-4 ortho fraction (1, 3, or 9 mg), a reconstituted 0-4 ortho fraction (9.97 mg), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153; 1 or 9 mg), 2,3,7,8-TCDD (1 microg; positive control) or corn oil (1 ml; vehicle control). One group did not receive a promotion treatment. All exposure groups exhibited a significantly increased volume fraction of the liver occupied by hepatic foci positive for the placental form of glutathione-S-transferase-p compared to the corn oil control, except for the groups treated with 0-1 ortho fraction and 1 mg PCB 153/kg body wt/week. Approximately 80% of the total tumor promoting capacity of the reconstituted 0-4 ortho fraction could be explained by the 2-4 ortho PCB fraction while the 0-1 ortho fraction had only a negligible contribution. These results suggest that the majority of the tumor promotion potential of PCB mixtures resides in the non-dioxin-like fraction, which is not taken into account in the toxic equivalency factor (TEF) approach for risk assessment of PCBs. This may result in an underestimation of the tumor promotion potential of environmental PCB mixtures.

Caries assessment and restorative treatment thresholds reported by Swedish dentists.

The aim was to study any variability in approximal and occlusal caries diagnoses and restorative treatment decisions among Swedish dentists. The material consisted of a pre-coded questionnaire sent to a random sample of 923 dentists with 4 items concerning approximal and occlusal caries diagnosis and restorative treatment decisions. Responses were received from 651 (70.5%) dentists. In an adolescent with low caries activity and good oral hygiene, more than 90% of the dentists stated that they would not automatically restore a primary approximal caries lesion if its radiographic appearance did not show obvious progression in the outer 1/3 to 1/2 of the dentin. Moreover, 67% of the dentists would only consider immediate restorative treatment of an occlusal surface if obvious cavitation and/or radiographic signs of dentin caries could be observed. When diagnosing questionable occlusal caries, the dentists largely relied on the radiographic appearance. Concerning both approximal and occlusal caries, the threshold for restorative treatment differed between the metropolitan regions in Sweden, and younger more often than older dentists would postpone restorative treatment of approximal caries until the lesion had reached a relatively advanced stage of progression. The responses also showed that dentists in private practice would restore approximal caries at an earlier stage of progression than the dentists in the Public Dental Health Service.

Left frontal activation during a semantic categorization task: an fMRI-study.

In the present study we measured brain activation, with functional magnetic resonance imaging (fMRI) during the execution of a covert semantic categorization task. This involves activation of working memory and internal concept generation. Previous brain imaging studies of covert verbal fluency have shown widespread activation in the frontal and temporal lobes, and anterior cingulate. However, most of these studies have employed simple stimulus tasks with repetition of words e.g., beginning with a certain letter of the alphabet. Moreover, the subject is typically cued (either visually or auditory) every 2-5 second. In the present study we used a "single-cue" instruction at the beginning of each activation period where the subject was instructed to internally generate category specific names related to: "States in the USA," "UK Soccer clubs," and "Male names" during 54s periods. The three activation periods were compared to three baseline periods in which the subject was instructed to imagine mentally "lying on a beach and looking at the sky." Functional MRI was performed with a 1.5T Siemens Vision scanner. Initial TIW 3D FLASH scanning of anatomy was done, and thereafter, serial imaging with 60 BOLD sensitive echo planar whole brain measurements were done during the active and passive tasks. Main activation areas were found in the left middle frontal gyrus, partially overlapping with Brodmann area 9. This is in agreement with previous studies of increased activation in the left frontal lobe, and may indicate a left frontal neural network for accessing the mental lexicon.

A mutational analysis identifies three functional regions of the spindle pole component Spc110p in Saccharomyces cerevisiae.

The central coiled coil of the essential spindle pole component Spc110p spans the distance between the central and inner plaques of the Saccharomyces cerevisiae spindle pole body (SPB). The carboxy terminus of Spc110p, which binds calmodulin, resides at the central plaque, and the amino terminus resides at the inner plaque from which nuclear microtubules originate. To dissect the functions of Spc110p, we created temperature-sensitive mutations in the amino and carboxy termini. Analysis of the temperature-sensitive spc110 mutations and intragenic complementation analysis of the spc110 alleles defined three functional regions of Spc110p. Region I is located at the amino terminus. Region II is located at the carboxy-terminal end of the coiled coil, and region III is the previously defined calmodulin-binding site. Overexpression of SPC98 suppresses the temperature sensitivity conferred by mutations in region I but not the phenotypes conferred by mutations in the other two regions, suggesting that the amino terminus of Spc110p is involved in an interaction with the gamma-tubulin complex composed of Spc97p, Spc98p, and Tub4p. Mutations in region II lead to loss of SPB integrity during mitosis, suggesting that this region is required for the stable attachment of Spc110p to the central plaque. Our results strongly argue that Spc110p links the gamma-tubulin complex to the central plaque of the SPB.

Effect of sucralfate on induced chemical cystitis in rabbits.

OBJECTIVE: To study the histological effect of locally applied sucralfate on the urinary bladder in rabbits with chemically induced cystitis. MATERIALS AND METHODS: Sucralfate (1 g dissolved in 10 mL saline) was instilled into the bladders of six rabbits, while four controls had no instillation. The procedure was repeated 4 days later and followed immediately by 10 mL of 2% formaldehyde infused into the bladder and retained for 10 min in all 10 rabbits. After careful flushing with saline, 10 mL sucralfate solution was again instilled in the study group and 10 mL of saline only in the control group. On day 6, the sucralfate instillation was repeated in the six treated animals. All the rabbits were then killed on day 8-9, their bladders removed and examined macroscopically and histologically. RESULTS: Formaldehyde instillation was quickly followed by gross haematuria in all animals. It subsided in the group treated with sucralfate, but not in the controls. Examination revealed only slight changes in the former group, but severe inflammatory lesions in the latter. CONCLUSIONS: Intravesically instilled sucralfate protected rabbit bladder urothelium against chemically induced cystitis. Clinical trials of intravesical sucralfate seem warranted in patients irradiated for pelvic cancer or with severe cystitis caused by cytotoxic drugs.

Twenty years' colonoscopic surveillance of patients with ulcerative colitis. Detection of dysplastic and malignant transformation.

BACKGROUND: Endoscopic cancer surveillance in patients with ulcerative colitis has been performed for almost 3 decades. There is still no consensus on its clinical value. METHODS: This study evaluates a 20-year prospective study of 143 patients with extensive ulcerative colitis and a disease duration exceeding 10 years. Colonoscopy with double biopsy specimens from nine locations of the colon was performed every 2nd year. Biopsy specimens showing dysplasia were reviewed at the end of the study. RESULTS: Through the surveillance dysplasia/cancer was detected in 55 patients; 7 of these patients had carcinomas, and 2 were in a possibly curable stage (Dukes A). The predictive value of low-grade dysplasia for either high-grade dysplasia or cancer was 41%. CONCLUSIONS: Although impaired by limiting factors, colonoscopic surveillance of chronic extensive colitis may identify patients with dysplasia and thereby prevent malignant transformation.

Phantom limb imaginary fingertapping causes primary motor cortex activation: an fMRI study.

A conventional 1.0 T MR-scanner was used to detect signal intensity changes in blood oxygenation level dependent-sensitive acquisitions of motor cortex during real (left hand) and imaginary (right hand) fingertapping in a man who had his right arm amputated. The subject was instructed alternately to move the intact left hand fingers and to imagine tapping his 'fingers' on the amputated right hand. Activated areas were detected using a cross-correlation technique with superimposition of highly correlated voxels on to a corresponding high resolution, anatomical 3D image. Activation was observed in the right motor cortex during fingertapping with the intact left hand, and a corresponding activation in the left motor cortex for imaginary movements of the amputated right hand fingers.

C-erb-b2/int-2 amplification appears faster in breast-cancer patients receiving second-line endocrine treatment.

We have examined the appearance of c-erb-b2 and int-2 amplification in 2 different groups of breast-cancer patients. The groups differed with regard to their clinical status in that one group was receiving first-line endocrine treatment (tamoxifen) whereas the second was receiving second-line endocrine treatment (after failing on tamoxifen). The latter group of patients showed clinicallya a more advanced disease (higher frequency of stage-IV as compared to stage-III disease). Consecutive tumor samples were obtained using fine-needle biopsies from individual tumor lesions of each patient every second or third month. Median time from diagnosis to the last biopsy for patients receiving tamoxifen was 25 months and, for patients receiving second-line treatment, 55 months. The presence of amplification was determined using semi-quantificative PCR. We found that both genes developed amplification during tumor progression. The appearance of amplification was more pronounced in the clinically more advanced patients receiving second-line treatment (p = 0.018).