[The analysis of structural magnetic resonance imaging manifestation of hippocampus based on voxel and spherical harmonic surface morphometry in mesial temporal lobe epilepsy].

Objective: To compare the hippocampal volume and local surface morphology changes in patients with mesial temporal lobe (mTLE) using the voxel-based morphometry and spherical harmonic methods respectively. Methods: A total of 66 patients (31 males and 35 females, age range from 17 to 48 (28±8) years) with mTLE and 80 age-and gender-matched controls (38 males and 42 females, age range from 19 to 46 (27±7) years) were retrospectively collected from July 2009 to February 2019 at Jinling hospital.. High resolution structural MRI of the whole brain, three-dimensional T1-weighted data(3DT1) were acquired from each subject. The changes of hippocampal volume and surface morphology were evaluated between mTLE groups and controls for observing the hippocampal atrophy pattern by using voxel-based morphometry and spherical harmonic shape descriptions point distribution model respectively. Pearson correlation analysis was conducted for observing the relationship between the morphological changes of hippocampus and disease duration. Results: Compared with the controls, hippocampal volume on the affected side in patients with mTLE was significantly reduced (Z-score:-1.55±0.57 vs 0.38±0.58, P<0.001) and negatively correlated with disease duration (r=-0.297, P=0.016). Furthermore, surface morphology analysis subtly showed that the atrophy of the affected hippocampus in patients with mTLE mainly located in the head, mesial lateral part and posterior tail of the hippocampus. Their displacement values were negatively correlated with disease duration (r=-0.336, P=0.006) and positively associated with the hippocampal grey matter volume (r=0.336, P=0.006). Conclusions: Voxel-based morphometry analysis reveals a global reduction in hippocampal volume, while the morphological measurement method based on surface shape can describe the local morphological changes of hippocampal atrophy.

Taxometric evidence of a dimensional latent structure for depression in an epidemiological sample of children and adolescents.

BACKGROUND: A basic phenomenological question of much theoretical and empirical interest is whether the latent structure of depression is dimensional or categorical in nature. Prior taxometric studies of youth depression have yielded mixed findings. In a step towards resolving these contradictory findings, the current taxometric investigation is the first to utilize a recently developed objective index, the comparison curve fit index, to evaluate the latent structure of major depression in an epidemiological sample of children and adolescents. METHOD: Data were derived from Mental Health of Children and Young People in Great Britain surveys. Participants were administered a structured diagnostic interview to assess for current depression. Parents (n = 683) were interviewed for children aged 5-16 years, and child interviews (n = 605) were conducted for those aged 11-16 years. RESULTS: MAMBAC (mean above minus below a cut), MAXEIG (maximum eigenvalue) and L-Mode (latent mode) analyses provided convergent support for a dimensional latent structure. CONCLUSIONS: The current findings suggest that depression in youth is more accurately conceptualized as a continuous syndrome rather than a discrete diagnostic entity.

Prevalence of haematuria positively associated with urine albumin excretion in Type 2 diabetes.

AIMS: Some guidelines or studies consider haematuria an indication for renal biopsy or a potential cause of albuminuria that precludes accurate assessment of urinary albumin excretion. This study examined the justification of excluding haematuria in interpreting urinary albumin excretion in patients with Type 2 diabetes and its associations with other diabetes-related variables. METHODS: Between May and November 2008, patients with Type 2 diabetes at a single centre with data on urinary albumin excretion and urinalysis in the same urine sample were recruited. Urinary albumin excretion was determined by urine albumin/creatinine ratio in spot urine. Diagnosis of haematuria was made by positive urine occult blood from 1+ to 4+ and/or presence of more than nine red blood cells/ml in urinalysis. Demographic, anthropometric, clinical and laboratory variables and diabetes-associated complications were analysed. RESULTS: In total, 743 patients were enrolled. Prevalence of haematuria among patients with normoalbuminuria, microalbuminuria, or macroalbuminuria was 8.7% (n = 13), 16.1% (n = 67) and 35.8% (n = 64), respectively. Urine albumin/creatinine ratio was significantly higher, while macroalbuminuria was more common in patients with haematuria (n = 144) than in those without (n = 599). Multiple regression analysis identified urine albumin/creatinine ratio (odds ratio 1.33, P = 0.01) and macroalbuminuria (odds ratio 2.66, P = 0.01) as the only independent predictors of haematuria. Moreover, urine albumin/creatinine ratio was an independent predictor of haematuria in the macroalbuminuria subgroup (odds ratio 1.30, P = 0.04). CONCLUSIONS: Increased urine albumin/creatinine ratio and macroalbuminuria were the only independent predictors of haematuria in patients with Type 2 diabetes, raising questions on the justifications of excluding haematuria in interpreting urinary albumin excretion in patients with Type 2 diabetes and including haematuria as an indication for renal biopsy in those with macroalbuminuria.

Correlations of IL-6 and IL-10 gene polymorphisms with childhood acute lymphoblastic leukemia.

OBJECTIVE: The aim of this study was to investigate the correlations between interleukin-6 (IL-6) and IL-10 gene polymorphisms with childhood acute lymphoblastic leukemia. PATIENTS AND METHODS: Specimens were collected from 200 children with acute lymphoblastic leukemia (disease group) and 200 normal children (control group) in our hospital. DNA was extracted from peripheral blood nucleated cells in both groups to detect the gene polymorphisms rs2069830 and rs2069836 of IL-6, as well as rs3024489 and rs3024493 of IL-10. Then, the content of serum IL-6 and IL-10 was determined via enzyme-linked immunosorbent assay (ELISA). RESULTS: It was found that there were differences in the distribution of alleles of IL-6 gene polymorphism rs2069830 (p=0.000) and IL-10 gene polymorphism rs3024493 (p=0.007) between the disease group and control group. The frequency of T allele of IL-6 gene polymorphism rs2069830 was higher, while that of IL-10 gene polymorphism rs3024493 was lower in the disease group. Besides, the differences in the distribution of genotypes of IL-6 gene polymorphism rs2069830 (p=0.000) and IL-10 gene polymorphism rs3024493 (p=0.000) were also observed between the disease group and control group. Moreover, the disease group had higher frequencies of TT genotype of IL-6 gene polymorphism rs2069830 and TA genotype of IL-10 gene polymorphism rs3024493. The frequencies of dominant model of IL-6 gene polymorphism rs2069830 (p=0.048) and recessive model of IL-10 gene polymorphism rs3024493 (p=0.000) in the disease group were different from those in the control group. In addition, the frequency of CC + CT dominant model of IL-6 gene polymorphism rs2069830 was lower, and the frequency of TA + AA recessive model of IL-10 gene polymorphism rs3024493 was higher in the disease group. There were differences in haplotypes CG (p=0.001), CT (p=0.007), and TG (p=0.000) of IL-6 gene, as well as haplotypes AA (p=0.002) and AT (p=0.005) of IL-10 gene between disease group and control group. Furthermore, the content of IL-6 in the serum was associated with the genotypes of IL-6 gene polymorphism rs2069830 (p<0.05), whereas the children with acute lymphoblastic leukemia carrying CT genotype had remarkably higher content of serum IL-6. The genotypes of IL-6 gene polymorphism rs2069830 was notably related to white blood cell (WBC) (p=0.002), and the WBC level was higher in children with CT genotype. The genotypes of IL-10 gene polymorphism rs3024489 had prominent correlations with platelet (PLT) (p=0.043), and the children with AA genotype had a higher PLT level. In addition, the genotypes of IL-10 gene polymorphism rs3024493 were evidently correlated with hemoglobin, which was significantly higher in children carrying TA genotype. CONCLUSIONS: The gene polymorphisms of IL-6 and IL-10 are significantly correlated with the susceptibility to and pathogenesis of childhood acute lymphoblastic leukemia.

Regular Tai Chi Chuan exercise improves T cell helper function of patients with type 2 diabetes mellitus with an increase in T-bet transcription factor and IL-12 production.

BACKGROUND: Exercise has been shown to be beneficial in the treatment of type 2 diabetes mellitus (DM); its benefit to immune function, however, remains to be determined. OBJECTIVE: This study investigated the effect of a 12-week course of Tai Chi Chuan (TCC) exercise on T cell helper (Th) reaction in patients with type 2 DM. METHODS: A case-control study was performed in 30 pairs of patients with type 2 DM and normal age-matched adults. Fasting blood glucose, HbA1c, mediators (interleukin (IL)-12, IL-4 and transforming growth factor (TGF)beta) and transcription factors (T-bet, GATA-3 and FoxP3) of Th1/Th2/T regulatory (Treg) reaction were measured before and after a 12-week TCC exercise programme. RESULTS: Fasting glucose and HbA1c levels in the patients with type 2 DM were significantly higher than in age-matched controls before exercise. After TCC exercise, HbA1c levels in patients with type 2 DM significantly decreased (7.59 (0.32)% vs 7.16 (0.22)%; p = 0.047) and blood levels of IL-12 increased significantly (5.96 (1.10) vs 12.96 (3.07); p = 0.035). To study the molecular Th1/Th2/Treg reaction, patients with type 2 DM were found to have lower T-bet but not GATA-3 or FoxP3 expression than normal controls before TCC exercise. After the 12-week TCC exercise T-bet expression significantly increased in patients with type 2 DM. CONCLUSIONS: A 12-week TCC exercise programme decreases HbA1c levels along with an increase in the Th1 reaction. A combination of TCC with medication may provide an even better improvement in both metabolism and immunity of patients with type 2 DM.

[Clinical study on the relations of obstructive sleep apnea hypopneasyndrome and the degree and prognosis of coronary lesions].

Objective:The aim of this study is to discuss the relations between obstructive sleep apnea hypopnea syndrome (OSAHS) and severity and prognosis of coronary artery disease. Method:The OSAHS patients were divided into mild, moderate and severe groups according to Results of sleep monitoring. The severity of coronary artery lesion in each group was compared by counting the numbers of the lesion extension of coronary artery, calculating the Gensin score and evaluating the Thromblysis in myocardial infarction. The patients were followed up within 2 years, the incidence of major clinical cardiac adverse events was compared between each groups. Result:Three groups confirmed the numbers of the lesion extension of coronary artery and Gensin score increased, the Thromblysis in myocardial infarction reduced with the seriousness of OSAHS by coronary angiography (P<0.05). There was no statistical significance in compliance for oral use of three groups (P>0.05). Incidence of the main adverse cardiac events during two years in three groups were16.28%, 29.36% and 44.26%. Incidence of the main adverse cardiac events increased with the seriousness of OSAHS (P<0.05). Conclusion:The coronary artery pathologic change severity aggravated with the seriousness of OSAHS，and the incidence of the main adverse cardiac events increased with the seriousness of OSAHS.

Two-stage Turing model for generating pigment patterns on the leopard and the jaguar.

Based on the results of phylogenetic analysis, which showed that flecks are the primitive pattern of the felid family and all other patterns including rosettes and blotches develop from it, we construct a Turing reaction-diffusion model which generates spot patterns initially. Starting from this spotted pattern, we successfully generate patterns of adult leopards and jaguars by tuning parameters of the model in the subsequent phase of patterning.

The dominant negative effect of thyroid hormone receptor splicing variant alpha 2 does not require binding to a thyroid response element.

The functionally inactive thyroid hormone receptor splicing variant-alpha 2 (TRv alpha 2) can inhibit transcriptional activation by TR alpha 1 or beta 1, demonstrating a dominant negative effect (DNE). We examine here the three commonly proposed mechanisms, namely, competition for binding to thyroid hormone response elements (TREs), formation of inactive heterodimers, and squelching. A mutation introduced into the DNA-binding domain (DBD) of the TRv alpha 2 was designed to prevent its binding to TREs. In transient cotransfection studies, the DBD mutant has nearly the same DNE as does TRv alpha 2 on three different TRE-containing reporter genes. The DNE of TRv alpha 2 is also not reversed by cotransfection with excess retinoid X receptor-alpha. Extracts of COS cells cotransfected with TR alpha 1 and either TRv alpha 2 or DBD mutant at different ratios were analyzed by gel shift assays. Neither TRv alpha 2 or the mutant altered binding of TR alpha 1 to four radiolabeled TREs. TRv alpha 2 itself can inhibit constitutive transactivation by a thymidine kinase promoter-driven reporter construct. Our results suggest that TRv alpha 2 can function in a dominant negative manner without binding to a TRE, at least for certain TREs. It is concluded that the DNE of TRv alpha 2 may occur through another unrecognized mechanism, perhaps by binding to basal transcription factors.

Importance of the most proximal GC box for activity of the promoter of human thyroid hormone receptor beta 1.

We wish to localize the sequences required for transcriptional expression of the thyroid hormone receptor beta 1 (TR beta 1). Constitutive activity of the promoter of human thyroid hormone receptor beta 1 was assessed by transient transfection of deletion constructs attached to luciferase as reporter, into P19, GH3, HepG2, H19-7, and COS1 cells. A 40-base pair fragment of the beta 1 promoter including the TATA box induced minimal luciferase activity, which was considered basal activity. The activities of various lengths of the beta 1 promoter were estimated relative to the minimal promoter in five cell lines. The region between -130 and -40 was crucial for constitutive activity in all cell lines. Further deletion analysis in HepG2 cells showed that two regions mainly augmented the transcriptional activity of the minimal 40 base pair fragment. One region located at -115 to -93, which is highly GC-rich, included the most proximal of five putative GC boxes present in the whole 1325-base pair promoter. A second region contributing to expression of TR beta 1 in HepG2 cells is at -70 to -40. Mutation of the most proximal GC box strongly suppressed transactivity of the whole promoter in P19 and HepG2 cells. In contrast, mutations in the other GC boxes did not suppress transactivation in P19 cells and slightly suppress activation in HepG2 cells. In Schneider cells, which do not express Sp1, transactivity of the region distal to -40 is positively regulated by cotransfection with a vector expressing Sp1.(ABSTRACT TRUNCATED AT 250 WORDS)

Triiodothyroacetic acid has unique potential for therapy of resistance to thyroid hormone.

3,5,3,'-Triiodothyroacetic acid (Triac) has been used in therapy of resistance to thyroid hormone on an empirical basis and appears beneficial in some studies. We observed that the T3 analogs, Triac and 3,5,3'-triiodothyropropionic acid (Triprop), have a higher affinity for the thyroid hormone receptor-beta 1 (TR beta 1) than does T3 (2.7- and 1.8-fold, respectively), whereas the affinities of the three compounds for TR alpha 1 are the same. To evaluate whether T3 analogs would have a differential effect on TR beta 1 and TR beta 1 mutants and thus be a specific treatment for patients with resistance to thyroid hormone, we examined the induction of the transcriptional activation of wild-type (wt) TR alpha 1, TR beta 1, and mutant TR beta 1s by T3, Triac, and Triprop. The dose response of transcriptional activation by T3 analogs was measured by transient cotransfections with TRs and a rat malic enzyme-TRE fused to thymidine kinase (TK)-chloramphenicol acetyltransferase (CAT) in COS-1 cells. For TR alpha 1 wt, induction of CAT activity by T3 and Triac occurred at the same concentration. For TR beta 1 wt, Triac and Triprop showed a higher maximal activity than T3 (Tripro > Triac > T3) and reached 50% induction at a lower concentration than T3 (Tripro < Triac < T3). Induction of CAT activity in five mutant TR beta 1s (kindreds Mh, Mc, CL, Mf, and GH) was also analyzed. Even high levels of T3 analogs could not restore CAT activity to that of TR beta 1wt for any mutant. A dominant negative effect was produced by Mh, Mc, and Mf. Mutants CL and GH had a mild dominant negative effect depending on T3 analog concentrations and TREs. Cotransfection studies were performed using a rat malic enzyme-TK-CAT reporter plasmid to analyze the effects of hormones at near-physiological concentrations of T3 and Triac. Triac had a significantly higher transcriptional activation than T3 in Mc, CL, and GH, suggesting that Triac would have a beneficial effect to different degrees for different mutant TR beta 1s. Using mutants Mc and GH, further studies were carried out using rat GH and double palindromic and inverted palindromic TREs in COS-1 cells. On each TRE, 10 nmol/L Triac induced higher transcriptional activation in TR beta 1wt, mutant TR beta 1s, and TR beta 1wt plus mutant TR beta 1s (1:1 ratio) than the same dose of T3.(ABSTRACT TRUNCATED AT 400 WORDS)

Serum thyroglobulin in the follow-up of patients with treated differentiated thyroid cancer.

To determine the significance of serum thyroglobulin (Tg) level in terms of presence or absence of thyroid cancer, we evaluated available serum Tg data on and off T4 therapy in 180 patients with differentiated thyroid cancer who have now been followed up to 18 yr. The presence of cancer was established by radioiodine scans, x-rays, and clinical examination. Thirty-two patients with detectable serum Tg autoantibodies were excluded from this analysis. Tg was measured by RIA with a sensitivity of 1 ng/mL. Patients who had all stages of cancer, but who had no evidence of active disease after treatment, were grouped according to operative and 131I ablative therapy. In patients with a partial thyroidectomy with or without ablation, the presence of Tg did not indicate the presence of cancer since levels were often above either a 5 ng/mL or a 10 ng/mL cutoff. The presence of residual normal thyroid tissue decreases the diagnostic value of serum Tg assay. In patients who underwent near total (NTT) or total thyroidectomy (TT) and 131I ablation, 3 of 55 (5.5%) patients had Tg greater than 5 ng/mL and 1 of 55 (1.8%) patients had Tg greater than 10 ng/mL during therapy, whereas off therapy 13 of 57 (22.8%) patients had Tg greater than 5 ng/mL and 6 of 57 (10.5%) patients had Tg levels greater than 10 ng/mL. In this group of patients, a Tg level less than 10 ng/mL during suppressive therapy indicated the absence of apparent tumor in 54 of 55 (98.2%) of patients. Whereas sensitivity of the assay was increased by withdrawal of hormone, "false positives" increased especially at lower (3-6 ng/mL) cut-off levels. No cut-off value properly categorized all patients. These data suggest, that even in patients who underwent 131I ablation and total thyroidectomy and were thought to be cured, small foci of thyroid tissue which are undetectable by standard 2 mCi 131I scans may exist and produce some Tg. However, these residual cells do not appear to cause an adverse prognosis in most patients. In patients with recurrent or continued disease, during T4 treatment, Tg levels ranged between 2-21,000 ng/mL and 5 of 11 patients had a Tg less than 5 ng/mL. Off treatment, Tg levels ranged between 6-10,700 ng/mL and 3 of 13 patients had a Tg less than 10 ng/mL. In 4 patients Tg levels were less than 10 ng/mL on treatment but greater than 10 ng/mL off therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Functional analysis of a proline to serine mutation in codon 453 of the thyroid hormone receptor beta 1 gene.

Mutations in the gene encoding human thyroid hormone receptor beta (hTR beta) have been associated with generalized resistance to thyroid hormone (GRTH). This disorder is associated with significant behavioral abnormalities. We examined the hTR beta gene in a family with members who manifest inappropriately normal TSH, elevated free T4, and free and total T3. Sequence analysis showed a cytosine to thymine transition at nucleotide 1642 in one allele of the index patient's genomic DNA. This altered proline to serine at codon 453. The resulting mutant receptor when expressed in vitro bound DNA with high affinity, but the T3 affinity of the receptor was impaired. The mutant TR demonstrated a dominant negative effect when cotransfected with two isoforms of wild-type receptor and also in the presence of TR variant alpha 2 in COS-1 cells. Mutations of codon 453 occur more frequently than at other sites, and four different amino acid substitutions have been reported. Significant differences in phenotype occur among affected individuals, varying from normality to moderately severe GRTH. There is no clear correlation between Ka or in vitro function of the mutant receptor, and phenotype. This study extends the association between GRTH and illness, and indicates that early diagnosis and counseling are needed in families with TR beta 1 abnormalities.

Levothyroxine suppression of thyroglobulin in patients with differentiated thyroid carcinoma.

For patients with differentiated thyroid carcinoma, the appropriate degree of TSH suppression by levothyroxine (L-T4) is still unknown. To find the target level of TSH suppression, we analyzed the relationship between the degree of TSH suppression determined by third generation assay and thyroglobulin (Tg) response during the titration of the dosage of L-T4. Ninety-two patients with differentiated thyroid carcinoma (19 males and 73 females; age, 40.5+/-13.5, mean +/- SD) were included. All of the recruited patients had near-total thyroidectomy, 30-150 mCi 131I thyroid ablation, and negative Tg autoantibodies. They were classified into 3 groups. Group A was composed of 25 patients with local or distant relapse. Group B was composed of 12 patients without clinically detectable relapse, but Tg levels either above 2 ng/mL under L-T4 suppression or above 3 ng/mL off L-T4 therapy. Group C included 55 patients who had no active disease and Tg levels below 2 and 3 ng/mL during and off L-T4 suppression, respectively. Serum TSH and Tg were measured simultaneously at the end of 8-12 weeks of a certain dose of L-T4 therapy during dosage titration and also after withdrawal of L-T4 for 4-6 weeks for the total body scan. Wilcoxon signed ranks test was used to compare paired samples of Tg, and Spearman rank correlation was used to determine the correlation of relative changes in TSH to changes in Tg calculated by individual. The results showed that 1) Tg levels were significantly higher during the period off L-T4 therapy than on L-T4, therapy in all 3 groups (P < 0.01); 2) during L-T4, therapy, within the same treatment course, mean Tg levels were higher when TSH levels were normal than when TSH levels were suppressed, statistically significant in group A (P = 0.001), nonsignificant in group B (P = 0.09), and nonsignificant in group C (P = 0.30); and 3) when TSH was suppressed below normal, there was no correlation between the relative changes in TSH and Tg by individual in all 3 groups (P > 0.05). The data suggest a stratified postoperative thyroid hormone management of patients with differentiated thyroid carcinoma. TSH should be lowered to below normal in patients with active disease. If patients are clinically disease free with Tg levels below 2 ng/mL, TSH can be kept within the normal range. For the most controversial group B patients, it is recommended that the TSH be suppressed and be closely followed up.

DNA binding affinity of hTRbeta1 mutants as heterodimers with traps from different tissues.

Patients with generalized resistance to thyroid hormone (GRTH) show various organ-specific features, for example mental retardation, growth abnormalities, liver damage, delayed bone age or cardiac disorders. Could this reflect aberrant mutant thyroid hormone receptor beta1 (TRbeta1) heterodimerization with specific TR auxiliary proteins (TRAPs) from different tissues, altering the mutant's ability to transactivate tissue-specific genes? To answer this question, we examined the heterodimerization of TRbeta1 mutants and TRAPs of several rat tissues (cerebrum, cerebellum, liver, heart, lung, spleen, and kidney), and in vitro translated RXRalpha, beta and gamma by electrophoretic gel mobility shift assay (EMSA). Mutant TRbeta1 proteins, synthesized in reticulocyte lysate, were incubated with 32P rat malic enzyme (rME) thyroid hormone response elements (TRE) and nuclear extracts of rat tissues. The TRbeta1 mutants used were Mf (G345R), and GH (R316H). Both have non-detectable T3 binding affinity. GH has weak dominant negative effect and Mf has strong dominant negative effect. Two major bands were observed in EMSA. Cerebrum, cerebellum, lung and liver extracts formed a slower migrating band than a TR homodimer, while kidney extracts formed a faster migrating band, and heart and spleen extracts had both bands. There were no qualitative differences in heterodimerization between TRbeta1wt, and TRbeta1 mutants, when using tissue extracts and DNA in excess ratio to TR. We found that RXRalpha, beta, and gamma were differentially expressed in each rat tissue and formed heterodimer complexes with wild type (WT) TRbeta1. Scatchard analysis of affinity and capacity of the binding of TR-TRAP heterodimers to response elements was performed by competing with 2.5-, 5-, 10-, 25-, and 250-fold excess non-radiolabeled rME-TRE. When using kidney extract, the DNA binding affinity of heterodimers was significantly decreased both in wild type and mutant TRs, suggesting that the DNA binding affinity of the faster migrating band was lower than that of the slower migrating band. Mutant GH, which causes 'pituitary RTH' and shows weak dominant negative effect, tended to form heterodimers with lower DNA binding affinity than TRbeta1wt with all extracts. Mutant Mf, which has strong dominant negative effect, tended to show higher DNA binding affinity than TRbeta1WT. When the data were pooled for all tissues, GH and Mf were found to form heterodimers with significantly lower, or higher, affinity for TREs than TRbeta1wt. These results indicate that: 1) differences of DNA binding affinity of mutant TR-TRAP heterodimers to response elements in DNA play a part in its reduced or strong dominant negative effect; and 2) differences in formation of heterodimers with TRAPs present in tissues do not appear to explain the apparent tissue-specific and mutant-specific variations seen in RTH.

The prediction of late rectal complications following the treatment of uterine cervical cancer by high-dose-rate brachytherapy.

PURPOSE: This study aimed to correlate patient, treatment, and dosimetric factors with the risk of late rectal sequelae in patients with uterine cervical cancer treated with external beam radiation therapy (EBRT) and high dose rate intracavitary brachytherapy (HDRICB). METHODS AND MATERIALS: From September 1992 to December 1995, a total of 128 patients with uterine cervical cancer, who were treated and survived more than 12 months, were evaluated. After EBRT with 40-44 Gy/20-22 Fr/4-5 weeks to the whole pelvis, the dose was boosted up to 54-58 Gy with central shielding for patients with bilateral parametria of Stage IIb or greater. HDRICB consisted of three to four insertions at doses of 5-7.2 Gy (to Point A) at intervals of 1 week. Patient and treatment factors were analyzed using logistic regression analysis and the cumulative rectal biologic equivalent dose (CRBED) was calculated. RESULTS: After 30-75 months of follow-up (median, 43 months), 38 patients (29.7%) had late rectal sequelae. Patients who had Stage IIb-IVa disease, cumulative rectal dose (external RT + total ICRU rectal dose) greeater than 65 Gy, or age greater than 70 years had a high risk of developing late rectal sequelae. When 110 Gy was used as the cut-off value, 19.6% (10 of 51) of patients whose CRBED was less than 110 Gy had rectal complications, while 36.4% (28/77) of patients whose CRBED was greater than 110 Gy developed rectal complications. CONCLUSION: Risk factors of late rectal complications were advanced stage, age greater than 70 years, and cumulative rectal dose of greater than 65 Gy.

An artificial thyroid hormone receptor mutant without DNA binding can have dominant negative effect.

The syndrome of resistance to thyroid hormone (RTH) encompasses a heterogeneous group of conditions which are caused by mutations of thyroid hormone receptor beta 1 (TR beta 1). Mutations usually cluster in two regions of the ligand-binding domain. The mutant receptors can inhibit normal receptor activity in a dominant negative manner, consistent with the dominant mode of inheritance of RTH. Recent evidence suggested that this dominant negative effect (DNE) of the RTH mutants involves competition for DNA binding and emphasized the essential role of intact DNA binding activity for mutants in order to exert DNE. However, we found that a Cys73Ser substitution in the DNA-binding domain (DBD) of wild-type produces a TR which can inhibit the transcriptional activation by TR alpha 1, either in the presence or absence of T3, on three different TRE-containing reporter genes, in transient co-transfection studies. Co-expression of TRv alpha 2, a TR alpha splicing variant, can enhance this DNE. However, DNE was not observed on the negatively-regulated TSH alpha Luc reporter gene when wild-type and DBD mutant were co-transfected at equimolar ratios. The DNE of DBD mutant is not reversed by co-transfection with excess retinoid X receptor alpha. DBD mutant alone can also inhibit the transactivation from a TK-luciferase reporter gene either linked with rat malic enzyme thyroid response element, or not. These observations parallel those we previously observed using TRv alpha 2. Our results indicate that a DBD mutant can have DNE, possibly through a mechanism similar to that of TRv alpha 2, which may involve interference with basal transcription factors. The clinical significance of these DBD mutants is currently unclear, but it is logical to expect such mutants do occur in nature.

Enhanced responses to aerosolized bronchodilator therapy in asthma using respiratory maneuvers.

To determine if respiratory maneuvers may enhance the response to inhaled bronchodilator drugs, we evaluated the bronchodilator responses when isoproterenol was: inhaled as a bolus high (80 percent VC) compared to low (20 percent VC) lung volumes, and inhaled as a single 800 microgram dose compared to four 200 microgram doses given 20 min apart. Nine asthmatic subjects inhaled isoproterenol sequentially at high and low lung volumes on two separate days; 15 others inhaled single doses of 200, 400, 600, and 800 microgram isoproterenol on four separate days. FEV1, specific conductance (Gaw/VL), Vmax50%, and the slope of phase 3 of the single-breath nitrogen test (deltaN2/L) were measured 10 min after each dose. FEV1 and Gaw/VL increased and deltaN2/L decreased more following inhalation at high compared to low lung volume (P less than 0.05). Gaw/VL increased more in the group given 800 microgram in divided doses than the group given a single dose (P less than 0.05). These findings suggest that the bronchodilator response to isoproterenol may be enhanced by inhaling the drug in divided doses sequentially and by delivering the drug near maximal inspiration. An enhanced response after the latter maneuver may be due to more uniform distribution of the drug to airway receptor sites.

Turing model for the patterns of lady beetles.

We simulate the patterns on the hard wings of lady beetles using a reaction-diffusion equation based on the Turing model. A part of a spherical surface is used to approximate the geometry of the hard wings. Various patterns common to lady beetles in Taiwan can be produced on this curved surface by adjusting the parameters of the model.