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PubMed1993

Asp57-negative HLA DQ beta chain and DQA1*0501 allele are essential for the onset of DQw2-positive and DQw2-negative coeliac disease.

The genetic predisposition to coeliac disease is associated with the HLA DQw2 allele. Coeliac patients lacking the DQw2 allele are very rare and always exhibit the DR4-DQw3 haplotype. We performed oligotyping of polymerase chain reaction (PCR)-amplified DQA1 and DQB1 genes in six DQw2-negative and 30 DQw2-positive coeliac patients. The DQB analysis showed that all six DQw2-negative patients possessed the DQB1*0302 allele. The other DQB alleles found in five of these patients were DQB1*0501, DQB1*0604 and DQB1*0302. The DQ beta chains encoded from all these alleles have the replacement of aspartic acid residue at position 57 (Asp57), as well as the DQB1*0201 allele which was found in all 30 DQw2-positive coeliac patients. The DQw2-negative proband who lacked the homozygous Asp57 replacement exhibited the DQA1*0501 allele in the DQA1 gene. The DQA1*0501 allele was also found in 27 of the 30 DQw2-positive coeliac patients. Among this group of coeliacs, the four cases lacking the DQA1*0501 allele exhibited the homozygous Asp57 replacement in the DQ beta chain. Our results indicate that Asp57-negative DQ beta alleles are involved in both DQw2-positive and -negative coeliac patients. Moreover, when the Asp57-negative DQ beta chain is encoded from only one of the two DQB1 genes the DQA1*0501 allele is always present.

Alleles↗

PubMed2004

Negative correlation between negative symptoms of schizophrenia and testosterone levels.

We conducted a pilot study in 10 adult male schizophrenics, 5 with predominantly positive symptoms (group I) and 5 with predominantly negative symptoms (group II), and 10 healthy matched controls. No significant differences in serum levels of testosterone (T), dehydroepiandrosterone sulfate (DHEAS), estradiol, and cortisol were found between patients as a whole and controls, using radioimmunoassay. However, serum T and DHEAS levels were lower (P <0.05) in group II patients than in group I. Body hair and aggression scores also were lower (P <0.05) in group II. In a much larger sample, Shirayama and colleagues also showed that "moderate negative symptoms, but not low negative symptoms" correlated negatively with T (P <0.05), but positively with ACTH (P <0.05) and cortisol (P <0.01) levels in plasma. Neuroactive steroids, such as DHEAS, and other sex hormones, including their synthetic derivatives, may have an adjunctive role in reversing or slowing the progression of negative symptoms. Indeed, "DHEA augmentation" improved "negative (P <0.01), depressive (P <0.05), and anxiety (P <0.01) symptoms."

Adult↗

PubMed2000

A Na+/Ca2+ exchanger inhibitor, KB-R7943, caused negative inotropic responses and negative followed by positive chronotropic responses in isolated, blood-perfused dog heart preparations.

Effects of a Na+/Ca2+ exchanger inhibitor, KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl] isothiourea methanesulfonate), on the sinoatrial nodal pacemaker activity, atrial contractility and ventricular contractility were investigated in the isolated and blood-perfused right atrium and left ventricle of the dog. KB-R7943 (0.03- 3 micromol) induced negative inotropic effects and negative followed by positive chronotropic effects in the right atrium and negative inotropic effects in the left ventricle. Neither atropine nor hexamethonium affected the cardiac responses to KB-R7943. Propranolol attenuated the positive chronotropic response to KB-R7943 but imipramine did not. Tetrodotoxin potentiated the positive chronotropic response to KB-R7943 in 6 of 11 isolated atria. When NaCl infusion increased atrial contractile force and atrial rate, KB-R7943-induced negative inotropic and chronotropic responses were attenuated in a dose-dependent manner. CaCl2 infusion potentiated the negative chronotropic response to KB-R7943 but did not affect the inotropic response significantly. On the other hand, ouabain (17 nmol) attenuated the negative inotropic response, but not chronotropic response, to KB-R7943. These results suggest that KB-R7943-induced cardiac effects relate to the Na+ activity, probably mediated through the Na+/Ca2+ exchanger, and the Na+/Ca2+ exchanger modifies the pacemaker activity and myocardial contractility in the dog heart.

Animals↗

PubMed2006

Benefits of negative thinking and negative affect: analyses of answers to an open-ended question by Japanese undergraduates.

What are the benefits of negative thinking and negative affect? Although previous studies in evolutionary psychology, social psychology, and clinical psychology have clarified the question, there has been no definitive study asking people directly about the perceived benefits. In the present study, 119 Japanese undergraduates were asked how they recognized the benefits of negative thinking and negative affect. Their answers were analyzed qualitatively. The answers were arranged into 30 smaller categories and 12 superordinate ones. The benefits were divided into "benefits to the self" and "benefits to interpersonal relations". Finally, the conditions necessary for the negative thinking and negative affect being benign, and possible cultural differences, were discussed.

Adolescent↗

PubMed1999

Negative priming effects that are bigger than a breadbox: attention to distractors does not eliminate negative priming, it enhances it.

In a series of experiments, we examined the effect of requiring subjects to attend to distractors in a test of negative priming. This was accomplished by using a referent size-selection task in which subjects were instructed to name the larger animal and to ignore the smaller animal in a word pair. The result was a quadrupling of the standard negative priming effect, suggesting that negative priming not only occurs for attended distractors, it is actually enhanced. We demonstrated that this enhancement of the effect was not due solely to increased latencies in the referent size-selection task, because neither decreasing base response times in other referent size-selection tasks nor increasing base response times in typical color-selection tasks substantially affected the respective negative priming effects. Although these findings can be accommodated within current theories of negative priming, they challenge the basic assumption that the negative priming effect arises because the critical item was ignored or not attended to on the prime trial.

Attention↗

PubMedDate not supplied

Usefulness of proton pump inhibitor (PPI) maintenance therapy for patients with H. pylori-negative recurrent peptic ulcer after eradication therapy for H. pylori: pathophysiological characteristics of H. pylori-negative recurrent ulcer scars and beyond acid suppression by PPI.

BACKGROUND/AIMS: Problems after Helicobacter pylori (Hp) eradication therapy include recurrence of Hp-negative peptic ulcers. We investigated the pathophysiological characteristics of Hp-negative recurrent ulcer scars, and performed proton pump inhibitor (PPI) maintenance therapy as a new therapy for prevention of recurrence in patients with Hp-negative recurrence after Hp eradication and investigated its usefulness. METHODOLOGY: The subjects were 21 patients with Hp-negative recurrent peptic ulcers after Hp eradication (gastric ulcer: 19, duodenal ulcer: 2) and 25 patients with non-recurrent ulcers (gastric ulcer: 20, duodenal ulcer: 5). The mucosa from the ulcer scar lesion was endoscopically obtained from patients, and HE staining, CD68 immunohistochemical staining, and investigation of the mucosal expression levels of TNF-alpha and IFN-gamma were performed by ELISA. Patients with recurrence after eradication were divided into two groups at the time of ulcer scar after the first treatment, and received maintenance therapy: the intermittent treatment group that received lansoprazole (LPZ), 30 mg/day, on two days on weekends (gastric ulcer: 9, duodenal ulcer: 1) and the ranitidine (RAN) 150 mg/day daily treatment group (gastric ulcer: 8, duodenal ulcer: 1). RESULTS: Infiltration of CD68-positive inflammatory cells was observed in the lamina propria mucosae over the epithelial layer in ulcer scars of the Hp-negative recurrent ulcer group compared with the non-recurrent ulcer group, and TNF-alpha and IFN-gamma significantly increased (27.22+/-6.23 pg/mg, 52.12+/-5.41 pg/mg vs. 4.23+/-2.14 pg/mg, 7.11+/-3.06 pg/mg, P<0.001). In the RAN maintenance therapy group, the ulcer recurred within 10 months in all patients, while the ulcer recurred in only one patient in the intermittent LPZ treatment group. CONCLUSIONS: These results suggested that the pathophysiological characteristic of Hp-negative recurrent ulcer scar lesions after eradication was infiltration of inflammatory cells, mainly monocytes/macrophages, in the lamina propria mucosae over the epithelial layer, and this may be a key factor in ulcer recurrence. Furthermore, intermittent PPI therapy using LPZ may be a useful maintenance therapy for prevention of recurrence in these cases.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2005

[Protein a production in coagulase-negative or clumping factor (CF)-negative isolates of Staphylococcus aureus].

The aim of study was to determine a production of proteinA in coagulase-negative Staphylococcus aureus (CNSA) or CF-negative S. aureus (CFNSA) strains. 59 CNSA and 18 CFNSA strains were isolated between 1997 and 2003 from different clinical specimens. The Protein A production was determined by immunoblotting method. The presence of protein A gene (spa) was investigated using the polymerase chain reaction (PCR). Two sets of phages and RFLP (Restriction Fragment Lenth Polymorphism) of coa gene method were used for typing strains. The results proved that the lack of ability of protein A production occurs more frequently in protein A-negative CFNSA strains with compare to the CNSA, which are protein A-positive for the majority of strains. Deficiencies of protein A, doesn't seem to be caused by the loss of spa gene. Protein A-negative CFNSA strains have phagotypes, RFLP and antibiotic resistant patterns which differ them from protein A-negative CNSA strains. Almost all of protein A-negative CFNSA and CNSA strains are resistant to methicillin.

Coagulase↗

PubMed2006

Negative colposcopic biopsy after positive human papilloma virus (HPV) DNA testing: false-positive HPV results or false-negative histologic findings?

We studied histologic examination-related factors contributing to false-negative colposcopic biopsy results. Patients positive for high-risk human papillomavirus (HPV) DNA with negative cervical histologic findings were identified between January 2002 and December 2003. Three additional H&E-stained levels were obtained when the original diagnosis was confirmed on review. Patients with atypical squamous cells of undetermined significance (ASC) Papanicolaou test results, positive HPV DNA results, and negative cervical histologic findings accounted for 4.5% of all ASC smears submitted for HPV DNA testing. Slides and tissue blocks were available for 95 cases; 4% had focal HPV infection or mild dysplasia. When deeper levels were examined, 31% had clinically significant lesions: HPV infection or cervical intraepithelial neoplasia (CIN) 1, 19%; CIN 2/3, 8%; and dysplasia, not otherwise specified, 3%. Of the remaining patients, follow-up revealed squamous abnormalities in 25%. About 5% of patients with positive HPV DNA results had a negative follow-up biopsy result. "False-negative" biopsies accounted for one third of cases. Additional levels should be obtained for discrepant results. Close follow-up is crucial when the initial biopsy result is negative because a small number of patients will have squamous abnormalities in subsequent studies.

Biopsy↗

PubMed1999

A practical problem with calculating the false-negative rate of Papanicolaou smear interpretation by rescreening negative cases alone.

BACKGROUND: Rescreening negative Papanicolaou (Pap) smears alone is the most commonly employed method of determining the false-negative rate (FNR) or the false-negative proportion for a laboratory. Acceptable FNRs have been proposed, and the number of slides needed to be rescreened to demonstrate a statistically significant difference in FNRs has been determined. The authors sought to determine the range of FNRs this method can measure and, by implication, the value of this method. METHODS: A literature review and an analysis of the FNRs this method can generate was performed. RESULTS: If one assumes that the FNR of review is the same as that of initial screening, the maximum measured FNR is only 25%, even with a true FNR of anywhere from 0-100%. In fact, as a laboratory's FNR increases over 50%, the measured FNR decreases back to zero. This range of FNRs corresponds very closely to the published range of FNRs of 1.6-28%. Because many authorities believe that 5% may be the lowest achievable FNR, the entire possible range of measured FNRs is only 5-25%. In this setting, a statistically significant difference of 20% is meaningless, and a statistically significant difference of 10% can only be achieved by laboratories with an initial FNR of less than 15%, and actual changes in FNR that are much greater than 10%. CONCLUSIONS: FNRs determined by review of negative smears without abnormal smears generate unreliable and potentially seriously misleading results. Current methodologies exist for more accurately determining the FNR of Pap smear screening by incorporating abnormal smears into the review process. There is little justification for further review of negative Pap smears alone as a method for determining the FNR of a laboratory. Cancer (Cancer Cytopathol)

False Negative Reactions↗

PubMed1995

High grade squamous cervical lesions following negative Papanicolaou smears: false-negative cervical cytology or rapid progression.

The cervical cytologic finding of a high grade squamous intraepithelial lesion (HGSIL) or carcinoma shortly following a negative smear is unusual. To determine if such cases are due to screening errors, inadequate sampling, or rapidly progressive lesions, a review of negative smears (immediately preceding a diagnosis of HGSIL or carcinoma by at most 2 yr) was performed on 17 patients (all such patients in our 1990-92 files, representing 6% (17/290) of such diagnoses). The time between negative smear and positive result averaged 9.3 mo. Eighty-eight percent of these patients had prior histories of a cytologic abnormality. Upon review, 16 of 17 "negative" smears contained a cytologic abnormality. Atypical immature squamous metaplastic type cells (AISMTs) were found in 11 of 16 cases, atypical squamous cells or slight dysplasia were found in 5 of 16, HGSIL was found in 5 of 16, and atypical cells of undetermined type and origin were noted in 1 of 16. Combinations of the above diagnoses were present in 6 of 16 cases. The number of abnormal cells per slide was estimated, with < 10 cells in 1 case, < 50 in 4 cases, 50-100 in 7 cases, 100-200 in 3 cases, and > 200 in 1 case. In this study, screening and/or evaluation errors were the dominant cause of false-negative cytologic diagnoses, with AISMTs accounting for the most commonly missed or misinterpreted cells. These cells are small and have hyperchromatic nuclei with elevated nucleus to cytoplasmic ratio and nuclear irregularities.

Adult↗

PubMed1999

Slow EEG potentials (contingent negative variation and post-imperative negative variation) in schizophrenia: their association to the present state and to Parkinsonian medication effects.

Between warning signal (S1) and imperative signal (S2), the EEG shifts negatively (contingent negative variation, CNV) reflecting preparation and expectancy. Reduced CNV and continued negativity after S2 (post-imperative negative variation, PINV) have been repeatedly found in schizophrenic patients and have been interpreted as a deficit in attentional processes (CNV) and as uncertainty about the correctness of one's own response to the S2 (PINV). Recent studies obtained a CNV reduction specifically at central sites but not at frontal ones. The present study investigated whether these alterations of slow negative potentials depend on present state of symptoms, on the particular task used, and on neuroleptic medication. Therefore, out-patients and in-patients were studied, two different S1-S2 tasks were used, and the control groups were healthy subjects and patients with Parkinson's disease. The central CNV reduction was stable across tasks and across in-patients and outpatients. Frontal CNV was reduced in in-patients but in only one of the two tasks in outpatients. The schizophrenic patients' enhanced PINV was larger contralaterally than ipsilaterally to the responding hand, correlated with medication, and occurred in similar way in patients with Parkinson's disease. Thus, the PINV increase might reflect the Parkinsonian side effects of the anti-psychotic medication. In contrast, the central CNV reduction appears as a stable marker of schizophrenia, the frontal CNV reduction as a state-dependent effect. The central CNV reduction might reflect impairment in forming stable stimulus-response associations, the relative frontal enhancement might reflect the out-patients' attempt at compensating that impairment.

Adult↗

PubMed2025

Reconsidering the definition of triple-negative breast cancer in the immune checkpoint inhibitor era: an optimal cut-off value for hormone receptor percentage of HER2-negative invasive breast cancer.

The optimal cut-off values of estrogen receptor (ER) and progesterone receptor (PgR) expression to define the positivity of ER and PgR have been under discussion for over a decade but remain controversial. The American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) and the St. Gallen International Expert Consensus recommended that breast cancers with ≥1% of ER or PgR expression should be considered hormone receptor (HR)-positive tumors but ER/PR expression of 1% to 10% should be reported as HR-low positive; however, among HER2-negative disease, data on the overall benefit of adjuvant endocrine therapies for patients with HR-low positive disease is limited, resulting in the revisiting of the definition of triple-negative breast cancer (TNBC). Defining HR-low positive disease by better understanding the biology is essential because of the recent advancement of neoadjuvant and adjuvant systemic therapy strategies, including immune checkpoint inhibitors (ICIs) for TNBC. Additionally, identifying who should be treated with adjuvant endocrine therapy, particularly those who have HR-low HER2-negative disease, which is currently treated as TNBC without adjuvant endocrine therapy, is a clinical unmet need. In clinical practice, treating physicians have tailored systemic treatment strategies using other clinical and pathological factors (i.e., age, grade, Ki-67, tumor size, lymph node involvement). There is no universal practice to treat patients with HR-low HER2-negative breast cancer. This review summarized the currently available data to define the clinically relevant optimal cut-off values of ER/PgR in neoadjuvant- and adjuvant-setting. We recommend considering creating a novel category of triple-negative like breast cancer (TN-like BC), which will require a therapeutic strategy different from conventional TNBC.

Humans↗

PubMed2005

Probability of axillary lymph node metastasis when sentinel lymph node biopsy is negative in women with clinically node negative breast cancer: a Bayesian approach.

BACKGROUND: Although sentinel lymph node biopsy(SLNB)is highly accurate in predicting axillary nodal status in patients with breast cancer, it has been shown that the procedure is associated with a few false negative results. The risk of leaving metastatic nodes behind in the axillary basin when SLNB is negative should be estimated for an individual patient if SLNB is performed to avoid conventional axillary lymph node dissection(ALND). METHODS: A retrospective analysis of 512 women with T1-3N0M0 breast cancer was conducted to derive a prevalence of nodal metastasis by T category as a pre-test(i.e., before SLNB)probability and to examine potential confounders on the relationship between T category and axillary nodal involvement. Probability of nodal metastasis when SLNB was negative was estimated by means of Bayes' theorem which incorporated the pre-test probability and sensitivity and specificity of SLNB. RESULTS: Axillary nodal metastasis was observed in 6.1% of T1a-b, 25.1% of T1c, 28.7% of T2, 35.0% of T3 tumors. Point estimates for the probability of nodal involvement when SLNB was negative ranged from 0.3-1.3% for T1a-b, 1.6-6.3% for T1c, 2.0-7.5% for T2, and 2.6-9.7% for T3 tumors with representative sensitivities of 80%, 85%, 90% and 95%, respectively. The risk may be higher when the tumor involves the upper outer quadrant of the breast, while it may be lower for an underweight woman. CONCLUSIONS: The probability of axillary lymph node metastasis when SLNB is negative can be estimated using a Bayesian approach. Presenting the probability to the patient may guide the decision of surgery without conventional ALND.

Adult↗

PubMed1997

A more accurate measure of the false-negative rate of Papanicolaou smear screening is obtained by determining the false-negative rate of the rescreening process.

BACKGROUND: The false-negative rate (FNR), or fraction, of Papanicolaou (Pap) smear screening has been proposed as a useful quality assessment measure. The FNR should account for the FNR of the rescreening process itself. The authors measured the FNR of the rescreening process by rescreening a set of abnormal smears. METHODS: A randomly selected group of negative (150) and abnormal (91) smears were rescreened in a blinded fashion. A diagnosis of atypical squamous cells of undetermined significance (ASCUS) or worse was used as a positive (abnormal) result. All discrepancies were confirmed by consensus review. The true FNR of screening Pap smears was calculated as: true FNR = calculated FNR/(1-FNR of rescreening). RESULTS: When rescreened, 17 originally negative cases were interpreted as ASCUS and 5 as unsatisfactory. Twenty-three originally abnormal cases (22 ASCUS and 1 low grade squamous intraepithelial lesion) were interpreted as negative. After consensus review, only 1 of the originally negative cases was believed to be ASCUS and 1 unsatisfactory; 18 of the 23 originally abnormal cases were believed to be rescreening errors and 5 of the 23 originally abnormal cases were believed to be false-positives. The FNR of Pap smear screening as traditionally calculated was 6.1%, which was slightly less than the laboratory's usual FNR. The FNR of review screening was 20.9%. The true FNR of Pap smear screening was 7.8% and the false-positive rate was 0.6%. CONCLUSIONS: The FNR of rescreening is not insubstantial. It can and should be measured by rescreening abnormal smears, and when taken into account yields a more accurate measure of the FNR of Pap smear screening.

Carcinoma in Situ↗

PubMed1992

Negative cognitive errors and positive illusions for negative divorce events: predictors of children's psychological adjustment.

This study examined the relations among negative cognitive errors regarding hypothetical negative divorce events, positive illusions about those same events, actual divorce events, and psychological adjustment in 38 8- to 12-year-old children whose parents had divorced within the previous 2 years. Children's scores on a scale of negative cognitive errors (catastrophizing, overgeneralizing, and personalizing) correlated significantly with self-reported symptoms of anxiety and self-esteem, and with maternal reports of behavior problems. Children's scores on a scale measuring positive illusions (high self-regard, illusion of personal control, and optimism for the future) correlated significantly with less self-reported aggression. Both appraisal types accounted for variance in some measures of symptomatology beyond that explained by actual events. There was no significant association between children's negative cognitive errors and positive illusions. The implications of these results for theories of negative cognitive errors and of positive illusions, as well as for future research, are discussed.

Adaptation, Psychological↗

PubMed1994

Negative symptoms in schizophrenia: considerations for clinical trials. Working group on negative symptoms in schizophrenia.

There is little agreement about the methodology of clinical trials of antipsychotic drugs in patients with negative symptoms. A literature review revealed wide variation in experimental design, rating scales and study duration. This reflects differing views as to the definition and response to treatment of negative symptoms. Some degree of standardization would improve comparability of studies and aid the development of new compounds. Patients included in such studies should have displayed negative symptoms for at least 6 months. Depressive symptoms, positive schizophrenic symptoms and extrapyramidal signs may all influence or be confused with negative symptoms and may respond to treatment; they should be at a low level at baseline and should be measured during the study period. Studies should last at least 8 weeks. Several scales are available for measuring negative symptoms and are reviewed; a global impression score should be used additionally.

Clinical Trials as Topic↗

PubMed2006

Helicobacter pylori-negative / API2-MALT1 translocation-negative low-grade MALT lymphoma.

A 71-year-old man with a Helicobacter pylori infection-negative and API2-MALT1 translocation-negative extranodal marginal-zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type of the stomach has been followed conservatively for over 5 years. The lesion has shown no major morphological changes or malignant progression into a diffuse large-cell type during the time course. The absence of genetic translocation of API2-MALT1 was confirmed with fluorescence in situ hybridization (FISH). The prognosis of H. pylori-negative and API2-MALT1 translocation-negative low-grade MALT lymphoma is unknown, and a standard treatment for such lymphoma has yet to be defined. The case of MALT lymphoma negative for both of the above factors that we report has shown no obvious rapid progression or malignant change over the long-term course. Although curative operation and/or chemoradiotherapy should still be discussed as the treatment of choice, the treatment of this type of lymphoma must be carefully determined on a case-by-case basis, according to its biological status and prognosis.

Aged↗

PubMedDate not supplied

Positive and negative symptoms in the psychoses: principal components analysis of items from the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms.

The present study investigated the factor structure of the items contained in Andreasen's scales for the assessment of positive and negative symptoms (SAPS and SANS) by use of a series of principal components analyses (PCAs) with oblique rotations of the axes. It was found that the structure could be summarized by three major components labeled negative symptoms, thought disorder, and delusions/hallucinations. Dimensionality could meaningfully be increased to five components. Negative symptoms was found to separate into two components that we labeled negative signs and social dysfunctions. The delusions/hallucinations factor could be separated into two components, delusions and hallucinations, with "loss of boundary" delusions being related to both factors. Delusions of persecution were independent of other symptoms. The thought disorder factor did not decompose meaningfully within the investigated dimensionality. A two-factor solution did not explain the correlation between symptoms adequately. The results do not support the simple dichotomy between positive and negative symptoms in psychosis, but suggest that a wider dimensional concept may be more useful in future studies.

Delusions↗