Immunoglobulin free light chain assay using latex agglutination

Summary Under normal biological conditions, immunoglobulin light chains are generally formed in conjunction with heavy chains; however, small quantities of free light chains are also produced. Thus, two types of immunoglobulin light chains may be identified; immunoglobulin-bound light chains and free light chains. In mature neoplastic B cells, immunoglobulin synthesis, including that of the free light chain, is generally increased. Furthermore, elevated free light chain levels also occur in the presence of renal glomerular and tubular impairment. Thus, the quantitative and qualitative measurement of free light chains is of considerable clinical benefit. Although methods for measurement of free light chains do exist, they are technically complicated and time consuming. Previously, we have reported a quantitative nephelometric immunoassay for measuring free light chain levels. We report here a refinement of this method using latex agglutination techniques. This new method enables quantitative measurement of free light chains in serum at levels as lows as 1 mg/l and may allow the clinical application of serum free light chain estimation.     

Usefulness of polyethylene glycol solution with dimethylpolysiloxanes for bowel preparation before capsule endoscopy

Background and Aim:  Capsule endoscopy (CE) is widely used for diagnosing small intestinal diseases. In some cases, however, observation of target sites is very poor during CE because of residues etc. Herein we report the usefulness of a preparation comprised of polyethylene glycol solution (PEG) for CE.
Methods:  This was a prospective, randomized, and single-blind study. Forty subjects, fasted for 12 h before CE, were randomized into two groups: 20 subjects in Group A were fasted only, whereas 20 in Group B received 1 liter (L) PEG with 200 mg dimethylpolysiloxane 3 h before CE. For evaluation, the observation period of the small intestine was divided into first and second halves. Subsequently, four investigators, blinded as to which group received the preparation, assessed the condition of the intestine using four rating scales in terms of 'residue' and 'intraluminal gas bubbles'. The effects of the preparation were statistically compared.
Results:  CE images were better in Group B than in Group A with respect to 'intraluminal gas bubbles' ( P  = 0.0038) in the first half of the observation period, as well as residue ( P  = 0.0087) and intraluminal gas bubbles ( P  = 0.0011) in the second half.
Conclusion:  Bowel preparation using 1 L PEG with dimethylpolysiloxane 3 h before CE significantly reduced residue and intraluminal gas bubbles, and was considered to be a useful method for CE.     

Organic nanotubes for drug loading and cellular delivery

Organic nanotubes made of synthetic amphiphilic molecules are novel materials that form by self-assembly. In this study, organic nanotubes with a carboxyl group (ONTs) at the surface were used as a carrier for the anticancer drug doxorubicin, which has a weak amine group. The IC(50) values of ONT for cells were higher than that of conventional liposomes, suggesting that ONTs are safe. The results showed that the drug loading of ONTs was susceptible to the effect of ionic strength and H(+) concentration in the medium, and drug release from ONTs was promoted at lower pH, which is favorable for the release of drugs in the endosome after cellular uptake. ONTs loaded with the drug were internalized, and the drug was released quickly in the cells, as demonstrated on transmission electron microscopy images of ONTs and the detection of a 0.05% dose of ONT chelating gadolinium in the cells. Moreover, ONT could be modified chemically with folate by simply mixing with a folate-conjugate lipid. Therefore, these novel, biodegradable organic nanotubes have the potential to be used as drug carriers for controlled and targeting drug delivery.     

Wedging of vertebral bodies at the thoracolumbar junction in asymptomatic healthy subjects on magnetic resonance imaging

Purpose

Wedging of the vertebral body on radiological examination is a valuable indicator of a vertebral compression fracture, although it can also be observed in subjects with no history of trauma. The purpose of this study was to elucidate the normative value of vertebral wedging at the thoracolumbar junction in asymptomatic healthy subjects for differential diagnosis of vertebral compression fractures using MRI.

Methods

A total of 115 subjects without back pain at the time of the examination and without history of spinal trauma was included (68 males, 47 females, mean age 49.5?years). They underwent MRI of the thoracic and lumbar spine, and the ratio of anterior vertical height to posterior vertical height of the vertebral body (APR) was determined from T10 to L2 on T2 weighted sagittal images.

Results

APR was 0.92?±?0.08 at T10, 0.92?±?0.08 at T11, 0.90?±?0.06 at T12, 0.89?±?0.06 at L1, and 0.90?±?0.07 at L2, indicating that vertebral bodies at the thoracolumbar junction appear wedge-shaped rather than rectangular. Males, thinner subjects, smokers, and subjects with abnormalities of the endplates such as a Schmorl nodule had a significantly smaller APR than females, fatter subjects, non-smokers, and those without endplate abnormalities.

Conclusion

The normative values of APR obtained in the present study can represent a valuable reference in the diagnosis of vertebral compression fracture to help prevent confusion with physiological vertebral wedging.     

Middle-colic artery aneurysm associated with segmental arterial mediolysis,successfully managed by transcatheter arterial embolization: Report of a case

An aneurysm of the middle-colic artery, associated with segmental arterial mediolysis (SAM), is a rare condition. This report describes a case of a middle-colic artery aneurysm that was associated with SAM. A 57-year-old man was admitted to our hospital because of severe abdominal pain. A rupture of a middle-colic artery aneurysm was diagnosed by computed tomography, and angiography showed that it may have been associated with SAM. The ruptured aneurysm was successfully treated with transcatheter arterial embolization. Transcatheter arterial embolization might be one of the best treatments for such a complicated aneurysm occurring in a visceral artery.     

Disulfide bond influence on protein structural dynamics probed with 2D-IR vibrational echo spectroscopy

Intramolecular disulfide bonds are understood to play a role in regulating protein stability and activity. Because disulfide bonds covalently link different components of a protein, they influence protein structure. However, the effects of disulfide bonds on fast (subpicosecond to approximately 100 ps) protein equilibrium structural fluctuations have not been characterized experimentally. Here, ultrafast 2D-IR vibrational echo spectroscopy is used to examine the constraints an intramolecular disulfide bond places on the structural fluctuations of the protein neuroglobin (Ngb). Ngb is a globin family protein found in vertebrate brains that binds oxygen reversibly. Like myoglobin (Mb), Ngb has the classical globin fold and key residues around the heme are conserved. Furthermore, the heme-ligated CO vibrational spectra of Mb (Mb-CO) and Ngb (Ngb-CO) are virtually identical. However, in contrast to Mb, human Ngb has an intramolecular disulfide bond that affects its oxygen affinity and protein stability. By using 2D-IR vibrational echo spectroscopy, we investigated the equilibrium protein dynamics of Ngb-CO by observing the CO spectral diffusion (time dependence of the 2D-IR line shapes) with and without the disulfide bond. Despite the similarity of the linear FTIR spectra of Ngb-CO with and without the disulfide bond, 2D-IR measurements reveal that the equilibrium sampling of different protein configurations is accelerated by disruption of the disulfide bond. The observations indicate that the intramolecular disulfide bond in Ngb acts as an inhibitor of fast protein dynamics even though eliminating it does not produce significant conformational change in the protein's structure.     

Predictive value of bone marrow accumulation of Tc-99m tetrofosmin for subsequent development of distant metastases in breast cancer

OBJECTIVE: We evaluated the predictive value of bone marrow accumulation of technetium (Tc)-99m tetrofosmin in patients with breast cancer for distant metastases in comparison with conventional prognostic factors such as clinical stage, tumor size, axillary lymph node (Node) status, and estrogen receptor (ER) status. METHODS: Bone marrow scans with Tc-99m tetrofosmin were performed on 64 patients with breast cancer who had no clinical evidence of distant metastases. Accumulation in the femoral marrow was classified into four patterns, no detectable, lower, higher, and intensively higher. Higher or intensively higher pattern was interpreted as abnormal. Thirty-six patients with abnormal accumulation (marrow-positive group) and 28 patients without abnormal accumulation (marrow-negative group) were enrolled in the follow-up study. The mean length of observation after scans was approximately 3 years. The predictive value of femoral marrow status and conventional prognostic factors for distant metastases was evaluated by statistical analysis. RESULTS: Univariate analysis showed a significantly higher incidence of subsequent bone metastases (36%>4%; P<0.005), and distant metastases (69%>18%; P<0.001) in the marrow-positive group when compared with the marrow-negative group. Conventional prognostic factors except tumor size were also significantly associated with the development of distant metastases; 77% in clinical stage 3>39% in clinical stages 1, 2, P<0.05; 64% in Node-positive>29% in Node-negative, P<0.01; and 70% in ER negative>27% in ER positive, P<0.005. These conventional factors were not significantly associated with bone metastases. The Cox proportional hazard ratio for bone metastases was markedly higher in femoral marrow status (hazard ratio=11.07). The distant metastases-free survival was significantly reduced in ER negative (P<0.0005), Node-positive (P=0.0215), and clinical stage 3 patients (P=0.0163). On the other hand, a more marked difference was observed in the femoral marrow status (P<0.0001). The hazard ratio for distant metastases was 2.44 in clinical stage, 2.74 in tumor size, 2.74 in Node, and 3.68 in ER, which were each independent prognostic factors associated with distant metastases. However, femoral marrow status was markedly associated with distant metastases (hazard ratio=5.27). CONCLUSIONS: Bone marrow accumulation of Tc-99m tetrofosmin can be a promising prognostic factor independent of conventional prognostic factors for predicting development of not only bone metastases but also distant metastases in breast cancer.     

Bladder cancer develops 6 years earlier in current smokers: Analysis of bladder cancer registry data collected by the cancer registration committee of the Japanese Urological Association

Objectives:   It is generally recognized that cigarette smoking is the most important risk factor for bladder cancer. The present study was undertaken to examine the relationships between smoking history of bladder cancer patients and the age of onset of bladder cancer and tumor characteristics.
Methods:   The present study examined the data for 5959 cases (4728 males and 1231 females) collected in the bladder cancer database of the Japanese Urological Association from 1999 to 2001. Patients were divided by smoking history into three categories as current non-smokers, current smokers and unknown smoking history. Relationship between smoking history and the age at diagnosis of bladder cancer, gender, T stage, grade, tumor size, tumor number and initial symptoms was analyzed
Results:   In both males and females the onset of bladder cancer is about 6 years (6.1 years in males and 5.9 years in females) earlier for current smokers than for current non-smokers. At the time of diagnosis, tumor stage was significantly higher in the current smokers group. The current smokers group tended to have larger tumor size.
Conclusions:   The finding of 6-year-earlier onset of bladder cancer among current smokers is of great importance to both health care and medical economics. It is essential to make people better informed concerning the need to quit smoking.     

Clinical outcome of tumor recurrence for Ta, T1 non-muscle invasive bladder cancer from the data on registered bladder cancer patients in Japan: 1999–2001 report from the Japanese Urological Association

Objective:   To characterize the clinical outcome in a large contemporary series of Japanese patients with newly diagnosed Ta, T1 non-muscle invasive bladder cancer who underwent transurethral bladder tumor resection with or without intravesical chemotherapy or Bacillus Calmette-Guérin (BCG) therapy.
Methods:   We developed a database incorporating newly diagnosed non-muscle invasive bladder cancer data and outcomes from a Japanese bladder cancer registry between 1999 and 2001 and identified a study population of 3237 consecutive patients who had complete data based on pathological features. Median patient age was 69.9 years.
Results:   The 1-year, 3-year, and 5-year overall recurrence-free survival rates were 77.0%, 61.3%, and 52.8%, respectively. In multivariate analyses, the multiplicity of bladder tumors, tumor size greater than 3 cm, pathological stage T1, tumor grade G3, and the absence of adjuvant intravesical instillation were independent risk factors for tumor recurrence. Overall, 1710 patients (52.8%) received intravesical instillation; chemotherapy in 1314 (76.8%) and BCG treatment in 396 (23.2%). In patients treated with intravesical chemotherapy in which an anthracycline chemo-agent was used in 90.5% of the cases, multivariate analyses demonstrated that male gender, multiple bladder tumors, a tumor size greater than 3 cm, and pathological stage T1 were associated with tumor recurrence.
Conclusions:   The accumulation and analysis of data from the Japanese National Bladder Cancer Registry made it possible to determine the clinical characteristics, management trends, and survival rates for the period studied. Further study with a dataset created from longer follow-up data would be warranted to analyze tumor progression and disease survival.