A study for the detection of kidney cancer using fluorescence emission spectra and synchronous fluorescence excitation spectra of blood and urine.

In this study, we compared different types of biomolecular markers in kidney cancer patients and in normal healthy controls, using fluorescence emission spectra and synchronous fluorescence excitation spectra. We were able to provide an accurate classification of the spectral features of kidney cancer patients relative to that of normal controls, in terms of the concentration ratios of biomolecules (viz., tryptophan, NADH, FAD, basic porphyrin, and acidic porphyrin) based on the intensity of their spectral peaks. The specificity and sensitivity of the method were 90%. The rationale of our current approach is to evolve an innovative protocol for the spectral characterization of in vitro optical analyses suitable for both small clinics and hospitals.

Differences in prostate cancer detection between Canadian and Saudi populations

Few studies have addressed racial differences in prostate cancer (PCa) detection between Western and Arabian countries, although PCa has a significantly lower prevalence in Arabic populations compared to Western populations. Therefore, an explanation of this difference is lacking. Serum prostate-specific antigen (PSA) is a valuable marker used to select patients who should undergo prostate biopsies, although the manner in which it is used may require adjustments based on the ethnic population in question. We investigated racial differences in the PCa detection rate between Canadian and Saudi populations. A retrospective analysis was performed of data collected prospectively over 5 consecutive years in urology clinics at the McGill University Health Center (MUHC) and King Saud University Hospital (KSUH). Men who had high (>4'ng/mL) or rising PSA levels and a negative digital rectal examination were eligible. A total of 1403 Canadian and 414 Saudi patients were evaluated for the study; 717 and 158 men, median age 64 and 68 years, were included in the MUHC and KSUH cohorts, respectively, P<0.0001). Median serum PSA, prostate volume, and PSA density values were 6.1'ng/mL, 47.3 g, and 0.12'ng·mL−1·g−1, respectively, for MUHC patients and 5.2'ng/mL, 64.5'g, and 0.08'ng·mL−1·g−1, respectively, for KSUH patients (P<0.0001, t-test followed by one-way ANOVA). In addition, the KSUH group had a significantly lower PCa detection rate among patients younger than 60 years of age and with PSA values <10'ng/mL.

A parallelism between spectral grading and Gleason grading of malignant prostate tissues.

Gleason score is the most common method of grading the virulence of prostate malignancy and is based on the pathological assessment of morphology of cellular matrix. Since this involves the excision of the tissue, we are working on a new, minimally invasive, non-contact, procedure of spectral diagnosis of prostate malignancy. In this preliminary in vitro study reported here, we have analyzed 27 tissue samples (normal control=7: benign=8: malignant=12) by Stokes' shift spectra (SSS) to establish a one-to-one correspondence between spectral grading and Gleason grading.

Optical biopsy of benign and malignant tissue by time resolved spectroscopy.

Pathological condition of malignant tissue could be analyzed by spectral domain or time domain spectroscopy, the two being the complementary to each other in optical biopsy (OB) of cancer. This paper reports results of time resolved emission spectroscopy (TRS) of 24 excised tissue samples of breast and prostate (normal control = 12; benign = 4; malignant = 8), employing a 390 nm, 100 fs, Ti-Sapphire laser pulses.The fluorescence decay times were measured using streak camera and the resultant data were fitted for single and bi-exponential decays with reliability of 97%. Our results show the distinct difference between normal, benign and malignant tissues mostly due to the emission spectra of Nicotinamide Adenine Dinucleotide (NADH), Flavin Mononucleotide (FAD) and also due to the heterogeneity of micro environments associated with the diseased tissues. In this short report, fit is also shown that TRS of breast tissues are similar to those of prostate tissues.

Differences in prostate cancer detection between Canadian and Saudi populations.

Few studies have addressed racial differences in prostate cancer (PCa) detection between Western and Arabian countries, although PCa has a significantly lower prevalence in Arabic populations compared to Western populations. Therefore, an explanation of this difference is lacking. Serum prostate-specific antigen (PSA) is a valuable marker used to select patients who should undergo prostate biopsies, although the manner in which it is used may require adjustments based on the ethnic population in question. We investigated racial differences in the PCa detection rate between Canadian and Saudi populations. A retrospective analysis was performed of data collected prospectively over 5 consecutive years in urology clinics at the McGill University Health Center (MUHC) and King Saud University Hospital (KSUH). Men who had high (>4'ng/mL) or rising PSA levels and a negative digital rectal examination were eligible. A total of 1403 Canadian and 414 Saudi patients were evaluated for the study; 717 and 158 men, median age 64 and 68 years, were included in the MUHC and KSUH cohorts, respectively, P<0.0001). Median serum PSA, prostate volume, and PSA density values were 6.1'ng/mL, 47.3 g, and 0.12'ng · mL(-1) · g(-1), respectively, for MUHC patients and 5.2'ng/mL, 64.5'g, and 0.08'ng · mL(-1) · g(-1), respectively, for KSUH patients (P<0.0001, t-test followed by one-way ANOVA). In addition, the KSUH group had a significantly lower PCa detection rate among patients younger than 60 years of age and with PSA values <10'ng/mL.

Prostate cancer screening in a Saudi population: an explanatory trial study.

The aim of this study is to explore the actual situation of prostate cancer in a cohort of healthy population in Saudi Arabia and to show the feasibility of screening for this disease using the internationally agreed criteria. This study was conducted in the city of Riyadh, in the outpatient clinics of four different health facilities. All men presented to the outpatient clinics during the period of study, from January 2008 to December 2008, were invited to participate in the study, in which they were subjected to PSA blood testing and digital rectal examination (DRE). When either test was abnormal, transrectal ultrasound and multiple prostatic biopsies were performed for confirmation of the results. A total of 2100 healthy males who met the inclusion criteria of the study were evaluated. The highest percentage of men with PSA>/=4 ng ml(-1) was in the age group 61-70, 51-60 years (42.7 and 31.8%, respectively). The number of subjects with an elevated PSA only was 172 (8.1%). Those having both elevated PSA and an abnormal DRE were 51 (2.4%). The total number referred to biopsy was 223. Fifty two subjects had a positive diagnosis of prostatic adenocarcinoma, which compromised 2.5% of the cohort studied. The cancer in 27 (52%) persons was organ confined, whereas in 14 (26.9%), it was metastatic. The prevalence rate of prostate cancer detected by screening was higher than expected and the disease was advanced. Larger community-based larger studies are highly warranted specially among high-risk groups.

CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry.

Store-operated Ca2+ entry is mediated by Ca2+ release-activated Ca2+ (CRAC) channels following Ca2+ release from intracellular stores. We performed a genome-wide RNA interference (RNAi) screen in Drosophila cells to identify proteins that inhibit store-operated Ca2+ influx. A secondary patch-clamp screen identified CRACM1 and CRACM2 (CRAC modulators 1 and 2) as modulators of Drosophila CRAC currents. We characterized the human ortholog of CRACM1, a plasma membrane-resident protein encoded by gene FLJ14466. Although overexpression of CRACM1 did not affect CRAC currents, RNAi-mediated knockdown disrupted its activation. CRACM1 could be the CRAC channel itself, a subunit of it, or a component of the CRAC signaling machinery.

The tensile properties of tension-free vaginal tape and cadaveric fascia lata in an in vivo rat model.

OBJECTIVE: To examine the tensile properties (break load and maximum average load), after in vivo implantation in a rat animal model, of tension-free vaginal tape (TVT) and cadaveric fascia lata (CFL), as pubovaginal slings of these materials have become popular for treating stress urinary incontinence. MATERIALS AND METHODS: Twenty Sprague-Dawley rats (300-400 g) had 1 x 2 cm strips of commercially available TVT and CFL implanted on the right and left anterior abdominal wall, respectively. Half of the animals were then killed at 6 weeks and the remainder at 12 weeks, after which the strips of TVT and CFL were removed and their tensile properties measured using a tensiometer. The tensile strength of TVT and CFL strips maintained only in normal saline served as controls. RESULTS: The TVT strips had a mean break load of 0.740 kg in the control and only 0.390 kg for CFL (P < 0.05). At 6 weeks the TVT material had a mean (sd) maximum average load of 0.634 (0.096) kg and a mean break load of 0.589 (0.249) kg, whereas the respective values for the CFL were 0.323 (0.198) and 0.167 (0.063) kg (P < 0.05). Similarly at 12 weeks, TVT had a greater mean maximum average and break load than CFL, at 0.742 (0.052) and 0.274 (0.126), and 0.737 (0.056) and 0.185 (0.128) kg, respectively. CONCLUSION: This is the first study to assess the tensile properties of the currently used sling materials, TVT and CFL, in an in vivo model. TVT has a greater break load and maximum average load than CFL; the tensile strength of these materials does not decrease with time.

Tissue reaction of the rabbit urinary bladder to tension-free vaginal tape and porcine small intestinal submucosa.

OBJECTIVES: To compare the histological tissue reactions of urinary bladder in close contact with polypropylene mesh tension-free vaginal tape (TVT) or porcine small intestinal submucosal (SIS) grafts, as the commercial availability of various materials has considerably simplified sling procedures for treating urinary incontinence, but erosion and infection after using artificial sling materials remain an important concern. MATERIALS AND METHODS: Thirty female New Zealand rabbits were randomized to three groups, i.e. group A (TVT, 12 animals), group B (SIS, 12) and group C (surgical control, six). Through a laparotomy under anaesthesia and an aseptic technique, the bladder was approached at its dome, where a 0.5 x 1 cm piece of TVT or SIS was fixed in direct contact with the bladder wall. The control group underwent only bladder manipulation with no material applied. Half the animals in each group were killed after 6 weeks and the other half after 12 weeks. The urinary bladder was harvested and examined histologically. RESULTS: The grafts in both groups were characterized by dense foreign-body type reactions and were mostly attached loosely to the bladder wall by a thin layer of fibrovascular tissue. More importantly, the bladder wall reactions showed no inflammation in all 12 animals in group A (TVT) but three of them had various grades of fibrosis. There was severe transmural inflammation in one animal in group B (SIS); one rabbit had grade I and two had grade II fibrosis. The controls, as expected, showed no bladder wall reactions. CONCLUSION: In this descriptive analysis of reaction types elicited on the urinary bladder by these grafts, both materials appeared to be safe. Although TVT elicited fewer and less severe adverse reactions, no statistical conclusions can be drawn. The clinical significance of these findings should emerge from long-term clinical data when they become available.

Bryostatin-1 specifically inhibits in vitro IgE synthesis.

Bryostatin-1, a macrocyclic lactone, is an antineoplastic agent that potently activates protein kinase C. Bryostatin-1 (Bryo) had an immunomodulatory effect on murine B cells in that it specifically inhibited IgE production. IgE levels were inhibited in a B cell dose-response curve, whereas IgM and IgG1 were induced by Bryo treatment. Taken together, ELISPOT and surface Ig staining data suggested that Bryo inhibition occurred at the level of class switching. RT-PCR and real time PCR data showed that this inhibition was achieved at an early step in switch recombination, namely, the appearance of Iepsilon germline transcripts. Although Bryo caused a delay in the proliferative response of IL-4/CD40 ligand trimer-stimulated B cells, CFSE studies revealed that the Bryo-mediated inhibition of class switching to IgE occurred independently of the number of division cycles. Notably, Bryo showed the same specific IgE inhibition in human B cells. This study provides evidence for a unique mechanism regulating IgE production possibly downstream of PKC by specifically modulating Iepsilon germline transcription.

Mature macrophage cell lines exhibit variable responses to LPS.

Bacterial lipopolysaccharide (LPS) is a potent activator of cells of the macrophage/monocyte lineage. Two mature macrophage cell lines, P388D1 and RAW264.7, exhibit very different biological responses to LPS. Although RAW264.7 cells release arachidonic acid from phospholipid in response to LPS stimulation, P388D1 cells do not respond in this manner. However, LPS primes P388D1 cells to release arachidonic acid in response to other stimuli. The goal of this work is to contrast the biochemical events that occur in LPS-treated P388D1 and RAW264.7 macrophages. Enzyme assays indicate that LPS treatment induces the activation of cytosolic PLA2 in RAW264.7, but not in P388D1 cells. Phorbol ester (PMA), a receptor-independent stimulus, also fails to induce arachidonic acid release from P388D1 cells, suggesting that these cells may have a defect in the signal transduction machinery that is common to LPS and PMA. This hypothesis is supported by the observation that the expression of the LPS receptors CD14 and CD11b/CD18 is similar on P388D1 and RAW264.7 cells. Western blot analyses indicate that the erk kinases are activated upon LPS treatment of RAW264.7 but not P388D1 cells. LPS-induced arachidonic acid release is reduced in cells treated with the MEK inhibitor PD98059, suggesting that activated erk kinases mediate the phosphorylation and activation of cPLA2 in this system. Interestingly, the p42 isoform of erk (erk2) appears to be activated in resting P388D1 cells. This observation indicates that the MAP kinase cascade may be constitutively activated in P388D1 cells which may in turn limit their ability to respond to LPS. Together, these data provide evidence that mature macrophages from different sources can exhibit variable responses to LPS and highlight the danger of making generalizations regarding the effects of LPS on macrophages.