Genome linkage screen for prostate cancer susceptibility loci: results from the Mayo Clinic Familial Prostate Cancer Study

Prostate cancer is one of the most common cancers among men and has long been recognized to occur in familial clusters. Brothers and sons of affected men have a twofold to threefold increased risk of developing prostate cancer. However, identification of genetic susceptibility loci for prostate cancer has been extremely difficult. Several putative loci identified by genetic linkage have been reported to exist on chromosomes 1 (HPC1, PCAP, and CAPB), X (HPCX), 17 (HPC2), and 20 (HPC20), with genes RNASEL (HPC1) and ELAC2 (HPC2) tentatively defined. In this study, we report our genome linkage scan in 160 prostate cancer families, using the ABI Prism Linkage Mapping Set Version 2 with 402 microsatellite markers. The most significant linkage was found for chromosome 20, with a recessive model heterogeneity LOD score (HLOD) of 4.77, and a model-free LOD score (LOD - ZLR) of 3.46 for the entire group of pedigrees. Linkage for chromosome 20 was most prominent among families with a late age of diagnosis (average age at diagnosis >/= 66 years; maximum LOD - ZLR = 2.82), with <5 affected family members (LOD - ZLR = 3.02), with presence of hereditary prostate cancer (LOD - ZLR = 2.81), or with no male-to-male transmission of disease (LOD - ZLR = 3.84). No other chromosome showed significant evidence for linkage. However, chromosomes 6 and X showed suggestive results, with maximum LOD - ZLR values of 1.38 and 1.36, respectively. Subset analyses suggest additional chromosomal regions worth further follow-up.     

Clinical presentation of primary progressive multiple sclerosis 10 years after the incidental finding of typical magnetic resonance imaging brain lesions: the subclinical stage of primary progressive multiple sclerosis may last 10 years

BACKGROUND: Subclinical multiple sclerosis (MS) has been identified incidentally at autopsy; apparently unaffected individuals with an affected twin have demonstrated magnetic resonance imaging (MRI) changes consistent with MS, and 'MRI relapses' are several times more common than clinical relapses. CASE DESCRIPTION: A 39-year-old, right-handed man underwent MRI and PET scanning in 1986 as a 'normal' control in a Parkinson's disease study, where his father was the proband. MRI indicated multiple areas of abnormal signal intensity in a periventricular and grey-white matter junction distribution. Repeated clinical evaluations over the next 10 years were unchanged until 1996, when he complained of progressive weakness of the right foot and clumsiness in the right hand. MRI now indicated a further area of high signal intensity in the right posterior cord at the level of C5/C6. There was mild pyramidal distribution weakness in the right leg with an extensor plantar response on the same side. Over the next five years there has been mild progression in weakness and fatigue and intermittent Lhermitte's phenomenon. At no stage has there been a history of relapse, cerebrospinal fluid examination was normal and evoked responses (visual and somatosensory) are normal. CONCLUSION: This case demonstrates the phenomenon of subclinical MS, unusually supported by prolonged clinical and MRI follow-up. The patient eventually became symptomatic nine years after MRI diagnosis and is following a primary progressive course. Although MRI is known to be sensitive in identifying subclinical 'attacks', the pattern illustrated here may actually be quite typical of primary progressive MS and is compatible with the later onset seen in this subgroup of patients.     

Evaluation of the clinical utility of cerebrospinal fluid (CSF) indices of inflammatory markers in multiple sclerosis

OBJECTIVES: Accumulating evidence indicates significant heterogeneity in MS and soluble (s) adhesion molecules are postulated as markers of disease activity. We sought to evaluate intrathecal production of these and other molecules across the clinical spectrum of MS. METHODS: CSF indices of IgG, sICAM-1, sVCAM-1, sE-selectin and sCD30 were calculated in 17 primary progressive (PPMS) patients, 15 secondary progressive patients (SPMS), 28 relapsing-remitting patients in relapse (RRMSR) and 14 RRMS patients in remission (RRMSNR) using commercially available ELISA kits. Patients had not received any immunomodulating therapy within the previous 6 months. MS patients were compared with 44 patients with non-inflammatory neurological diseases (NINDs). RESULTS: The most sensitive CSF index at a 90% level of specificity was for IgG which had 93% sensitivity in RRMSR and 92% sensitivity in RRMSNR. Corresponding sensitivity in PPMS and SPMS was 71% and 73% respectively. None of the other indices had sensitivity >50% apart from sVCAM-1 (64% in RRMSR and 52% RRMSNR) and sCD30 (53% in PPMS). CONCLUSIONS: Unsurprisingly the strongest association in MS was with the intrathecal production of IgG. Similar results in PPMS and SPMS may reflect comparable rates of progression in these 2 groups. Of the other molecules only intrathecal sVCAM-1 production is significantly associated with MS and only in relapsing-remitting disease.     

Endocrine and metabolic response in the human newborn to first feed of breast milk

The hormonal and metabolic response to the first feed of breast milk was studied in 12 infants at 4-6 hours of age. After the feed there was an increase in blood glucose concentration but no changes in the concentrations of lactate, pyruvate, alanine, or ketone bodies. The feed was followed by an increase in the concentrations of plasma insulin, growth hormone, gastrin, and enteroglucagon, but no change in levels of plasma glucagon or gastric inhibitory peptide. Several hormone systems are functionally active at birth and are stimulated by the first feed of milk.     

Seidel and India ink tests assessment of different clear cornea side-port incision configurations

Background

Post-cataract endophthalmitis has increased after introduction of clear cornea incisions (CCI). Laboratory models suggested that these incisions might not be competent at certain changes in intraocular pressure (IOP). Considering that side-port incisions (SPI) might behave similarly, the purpose of the present study was to determine the most stable side-port incision configuration.

Methods

Using four cadaveric human eyes, four different side-port incisions (SPI) were created in each cornea: 1.5 mm and 2.5 mm squared tunnel, 1.5 mm and 2.5 mm stab tunnel. Fluorescein was placed on the eye, and the IOP varied from 10 to 80 mmHg. IOP at which each SPI started leaking was recorded. In the second part of the study, India ink was applied to the corneal surface at normal IOP, and then rinsed with balanced salt solution (BSS). The ink influx was recorded by planimetry. IOP was elevated to 80 mmHg, ink was reapplied, and IOP was dropped to 0 mmHg. Ink influx was measured again. Histological examination was used to visualize ink inflow into each incision.

Results

There was no statistically significant difference in the IOP levels at which the different incisions leaked (p?=?0.52). A significant increase in the length of India ink ingress in all incision types was measured after IOP variation (p?<?0.05). The 2.5 mm squared incision showed the least increase in ink inflow in this test.

Conclusion

All incision types of SPIs tested exhibited similar resistance to leakage after IOP variation. Good resistance to wound leakage may not predict adequate resistance to the inflow of bacterial-sized particles into the wound.     

Modulation of implantation-associated integrin expression but not uteroglobin by steroid hormones in an endometrial cell line

In order to test the hypothesis that integrin and uteroglobin (UG) expression in cultured endometrial cells are affected by hormone treatment, Ishikawa-CH endometrial cancer cells were cultured and exposed to oestradiol or oestradiol and progesterone regimens and assayed using immunohistochemistry. We evaluated the intensity of immunohistochemical staining for the integrin monomers alpha(v) and beta1, the dimers alpha(v)beta3 and alpha(v)beta6, and for the secretory protein uteroglobin under various experimental conditions. Cells grown in control media stained positively for the integrin monomers alpha(v) and beta1, the dimer alpha(v)beta3, and for UG. Oestradiol and sequential oestradiol/progesterone reversibly suppressed staining for the dimer alpha(v)beta3. Hormone treatment had no effect on the staining of the beta1 and alpha(v) monomers or UG. The alpha(v)beta6 dimer antibody did not stain under any experimental treatment conditions. These data indicate that expression of the integrin complex alpha(v)beta3 is reversibly suppressed by oestradiol in Ishikawa cells and that these cells may be a good model for studying hormone-driven molecular changes in endometrium.