The pattern and frequency of t(14;18) translocation and immunophenotype in Asian follicular lymphoma

AIMS: Follicular lymphoma is frequently associated with t(14;18)(q32;q21) translocation. This study was undertaken to determine the pattern of Bcl-2, CD10 and Bcl-6 expression in relation to t(14;18) translocation in follicular lymphoma from a cohort of a multi-ethnic Asian population. METHODS AND RESULTS: Sixty-two cases of follicular lymphoma were retrieved for immunohistochemistry, and t(14;18) translocation analysis by polymerase chain reaction and fluorescent in-situ hybridization techniques. Bcl-2 expression was present in 74% of the cases. CD10 expression was also relatively low (61%), with decreasing frequency of expression in high-grade tumours. Bcl-6 protein was expressed in most of the tumours (88%) regardless of the tumour grade. The t(14;18) translocation was detected in 46 cases (74%) with an extremely high rate of t(14;18) translocation in ethnic Indian cases (100%). CONCLUSION: The frequency of t(14;18) translocation in this series of follicular lymphomas was higher when compared with previous Asian reports, but in accordance with European and North American findings. CD10 expression is strongly associated with a t(14;18) translocation event, but the overall CD10 expression was relatively low, possibly due to the high proportion of high-grade tumours in the series. t(14;18) translocation was not associated with Bcl-2 or Bcl-6 expression.     

Effect of chronic treatment with clozapine and haloperidol on 5-HT(2A and 2C) receptor mRNA expression in the rat brain

This study examined regional changes of 5-HT(2A and 2C) receptor mRNA expression in the rat brain after chronic administration of clozapine (1.5 mg/kg/day) and haloperidol (2.0 mg/kg/day) for 36 days. 5-HT(2A and 2C) receptor mRNA expression and distributions were detected by in situ hybridization after rats were sacrificed either 2 or 48 h after the last drug administration to examine both immediate and delayed effects following drug withdrawal. Following 2 h of drug withdrawal, it showed that clozapine administration significantly decreased 5-HT(2A) receptor mRNA, predominantly in the nucleus accumbens (65%), hippocampus (80%), lasteral septal nucleus (61%) and striatum (68%) compared to controls, whilst rebound increases were observed in most of these regions 48 h later. In contrast, no change in 5-HT(2A) receptor mRNA expression was found in the haloperidol treated groups either 2 h or 48 h after drug withdrawal. Clozapine also decreased 5-HT(2C) receptor mRNA expression in the posteromedial cortical amygdala (32%) and substantia nigra (35%) 2 h after the last drug administration, while rebound effects were also observed 48 h later. 5-HT(2C) receptor mRNA was only decreased in the substantia nigra at both 2 h (42%) and 48 h (54%) after the last haloperidol administration. Alterations in serotonin receptor expression in limbic system region such as the nucleus accumbens, hippocampus and lateral septal nucleus as well as the striatum may represent the specific regional targets that mediate the clinical effects of antipsychotics via the serotonin system.     

Phenotypic and population differences in the association between CILP and lumbar disc disease

Background

Lumbar disc disease (LDD) is one of the leading causes of disability in the working‐age population. A functional single‐nucleotide polymorphism (SNP), +1184T→C, in exon 8 of the cartilage intermediate layer protein gene (CILP) was recently identified as a risk factor for LDD in the Japanese population (odds ratio (OR) 1.61, 95% CI 1.31 to 1.98), with implications for impaired transforming growth factorβ1 signalling.

Aim

To validate this finding in two different ethnic cohorts with LDD.

Methods

This SNP and flanking SNPs were analysed in 243 Finnish patients with symptoms of LDD and 259 controls, and in 348 Chinese subjects with MRI‐defined LDD and 343 controls.

Results and conclusion

The results showed no evidence of association in the Finnish (OR = 1.35, 95% CI 0.97 to 1.87; p = 0.14) or the Chinese (OR = 1.05, 95% CI 0.77 to 1.43; p = 0.71) samples, suggesting that cartilage intermediate layer protein gene is not a major risk factor for symptoms of LDD in Caucasians or in the general population that included individuals with or without symptoms.Lumbar disc disease (LDD) is one of the leading causes of disability in the working‐age population. Radiological changes indicative of LDD are common, but only a proportion develops complications such as disc herniation and sciatica. Although the aetiology of LDD is not well understood, there is strong evidence for the involvement of both genetic and environmental factors.^1,2A recent study reported an association between LDD and a functional single‐nucleotide polymorphism (SNP) (rs2073711), +1184T→C, in exon 8 of the cartilage intermediate layer protein gene (CILP) in a Japanese group (odds ratio (OR) 1.61, 95% CI 1.31 to –1.98).³ The allelic change resulted in amino acid substitution Ile395Thr. CILP is expressed widely in intervertebral discs and its expression increases as disc degeneration progresses.³ CILP interacts directly with transforming growth factor (TGF)β1, inhibiting the TGFβ1‐mediated induction of extracellular matrix proteins such as aggrecan and collagen II.³ Functional studies showed that the C allele (coding for Thr395) increased binding and inhibition of TGFβ1, suggesting that regulation of TGFβ1 signalling by CILP plays a crucial role in the aetiology and pathogenesis of LDD.³Argument for a causal role would be strengthened if the same association could be replicated in a distinct population, and in clinical cases of LDD defined by MRI changes indicative of LDD in general. Therefore, we investigated the association between CILP polymorphisms and LDD in a Finnish sample with symptoms of LDD, and in a Chinese sample with only MRI‐defined LDD. These samples were informative in previous studies demonstrating association of LDD with the vitamin D receptor gene⁴ and the Gln326Trp (Trp2) allele of COL9A2⁵ in Chinese and the Arg103Trp (Trp3) allele of COL9A3 in Finns.⁶ Thus, the Chinese sample is comparable with the Finnish dataset, and a correlation can then be drawn with the Japanese dataset.     

Improved high-performance liquid chromatographic analysis of terazosin in human plasma

A simple, sensitive and reproducible high-performance liquid chromatography (HPLC) method was developed for the determination of terazosin in human plasma. The method involves a one-step single solvent extraction procedure using dichloromethane with a 0.25 ml plasma sample. Recovery values were all greater than 90% over the concentration range 0.25-100 ng/ml. Terazosin was found to adsorb to glass or plastic tubes, but this could be circumvented by using disposable plastic tubes. Also, rinsing the injector port with methanol after each injection helped to prevent any carry-over effect. The internal standard, prazosin, did not exhibit this problem. The method has a quantification limit of 0.25 ng/ml. The within- and between-day coefficient of variation and accuracy values were all less than 7% over the concentration range 0.25-100 ng/ml and hence the method is suitable for use in pharmacokinetic studies of terazosin.     

Specific detection of fungal pathogens by 18S rRNA gene PCR in microbial keratitis

Background  

The sensitivity and specificity of 18S rRNA polymerase chain reaction (PCR) in the detection of fungal aetiology of microbial keratitis was determined in thirty patients with clinical diagnosis of microbial keratitis.     

Elevated peritoneal fluid luteinizing hormone and prolactin concentrations in infertile women with endometriosis

In this study, we compared (Mann-Whitney U-test) the peritoneal fluid FSH, LH and PRL levels, measured by RIA, at the follicular and luteal phases of the menstrual cycle in women with (n = 43; age 25-44 years) and with no evidence of endometriosis (n = 35; age 25-39 years) who were considered as controls. Both follicular and luteal phase FSH concentrations of women with endometriosis were not statistically different (n = 22 vs 18; 0.32-5.8 vs 0.50-8.2 IU/l, P = 0.247; n = 13 vs 14; 0.6-6.5 vs 0.66-6.7 IU/l, P = 0.604) compared to their respective controls. In contrast to FSH, the concentrations of LH at follicular (n = 19 vs 17; 3.1-34.2 vs 2.3-12.2 IU/l, P = 0.01) and luteal (n = 17 vs 15; 2.1-95.4 vs 1.3-17.9 IU/l, P = 0.02) phases of the test group was significantly elevated at both phases of the cycle. With respect to differences in PRL concentrations at follicular phase no significant change (n = 21 vs 16; 1030-5800 vs 1305-4650 mIU/l; P = 0.255) was observed. The greatest difference in luteal PRL concentrations (P = 0.007) was obtained between the women with endometriosis and controls (n = 17 vs 17; 1895-8600 vs 1041-5000 mIU/l). The results suggest that disordered synchronization of neuroendocrine mechanisms controlling LH and PRL may be the underlying abnormality causing infertility in our group of patients with endometriosis.     

Properties of the temperament and character inventory in a Chinese sample

OBJECTIVE: To determine the influence of language and culture on the temperament and character (TCI) measure in a Chinese sample. METHOD: We translated the TCI into Mandarin and had a non-psychiatric sample of Malaysian Chinese subjects complete the TCI at baseline and at a 1-month retest, with subsets completing English or Mandarin versions alternatively or on both occasions. Analyses examine the TCI factor structure and any impact of language and culture on TCI scoring. RESULTS: We identified age, gender, occupation and language effects on TCI scale scores. Test-retest reliability was high and not compromised by language. Scale internal consistency was also high. Factor analyses of separate sets of TCI scales corresponded strongly to the structure identified in the TCI development studies. CONCLUSION: The results indicate that TCI is likely to have applicability to Chinese subjects, and argue against properties being constrained by the English language or by western culture.     

Differential cytostatic effect of sodium salicylate in human colorectal cancers using an individualized histoculture system

PURPOSE: Tumor metastasis is the major cause of colorectal cancer (CRC) mortality. Nonsteroidal antiinflammatory drugs (NSAIDs) such as aspirin have been shown to have an antineoplastic effect in CRC cell lines. Different patients, however, exhibit different chemosensitivity. In this study, we assessed the chemotherapeutic potential of sodium salicylate, an aspirin metabolite, by measuring its cytostatic effect in an individualized three-dimensional histoculture system. METHODS: Histocultured cancer tissues were treated with sodium salicylate at concentrations from 1 to 10 m M for 24 or 48 h. Inhibition of DNA synthesis was measured in terms of inhibition of bromodeoxyuridine (BrdU) incorporation.RESULTS: The concentration response of individual cancer tissues could be categorized into four groups ranging from the most to the least sensitive to sodium salicylate. Of 20 cancer tissues, 12 (60%) showed a concentration-effect relationship with sodium salicylate in the clinically relevant concentration range (IC50 1.2+/-0.4 to 3.8+/-0.5 m M). Doubling the exposure time decreased the IC50 in four specimens, suggesting that a similar inhibition might be achieved with a lower concentration over an extended time. None of the right-sided cancers was sensitive to sodium salicylate ( P=0.002). CONCLUSIONS: Sodium salicylate had a cytostatic effect on the majority of histocultured CRC tissues. The varying chemosensitivity of the cancers possibly reflected underlying differences, for example in relation to cancer site, thus emphasizing further the usefulness of this clinically relevant system in tailoring chemotherapy to the individual patient.