Mental health outcomes in elderly men with prostate cancer

ObjectiveTo examine the burden of mental health issues (MHI), namely anxiety, depressive disorders, and suicide, in a population-based cohort of older men with localized prostate cancer and to evaluate associations with primary treatment modality.Patients and methodsA total of 50,856 men, who were 65 years of age or older with clinically localized prostate cancer diagnosed between 1992 and 2005 and without a diagnosis of mental illness at baseline, were abstracted from the Surveillance, Epidemiology, and End Results–Medicare database. The primary outcome of interest was the development of MHI (anxiety, major depressive disorder, depressive disorder not elsewhere classified, neurotic depression, adjustment disorder with depressed mood, and suicide) after the diagnosis of prostate cancer.ResultsA total of 10,389 men (20.4%) developed MHI during the study period. Independent risk factors for MHI included age≥75 years (hazard ratio [HR] = 1.29); higher comorbidity (Charlson comorbidity index≥3, HR = 1.63); rural hospital location (HR = 1.14); being single, divorced, or widowed (HR = 1.12); later year of diagnosis (HR = 1.05); and urinary incontinence (HR = 1.47). Black race (HR = 0.79), very high-income status (HR = 0.87), and definitive treatment (radical prostatectomy [RP], HR = 0.79; radiotherapy [RT], HR= 0.85, all P<0.001) predicted a lower risk of MHI. The rates of MHI at 10 years were 29.7%, 29.0%, and 22.6% in men undergoing watchful waiting (WW), RT, and RP, respectively.ConclusionOlder men with localized prostate cancer had a significant burden of MHI. Men treated with RP or RT were at a lower risk of developing MHI, compared with those undergoing WW, with median time to development of MHI being significantly greater in those undergoing RP compared with those undergoing RT or WW.     

Are adult patients with Laron syndrome osteopenic? A comparison between dual-energy X-ray absorptiometry and volumetric bone densities

Severe short stature resulting from a deficiency in IGF-I is a prominent feature of Laron syndrome (LS). Although low bone mineral density (BMD) has been noted in LS patients examined by dual energy x-ray absorptiometry (DEXA), this technique does not take volume into account and may therefore underestimate the true bone density in patients with small bones. The aim of the present study was to evaluate the BMD yielded by DEXA in our LS patients using estimated volumetric values. Volumetric density was calculated with the following formulas: bone mineral apparent density (BMAD) = bone mineral content (BMC)/(area)(3/2) for the lumbar spine and BMAD = BMC/area(2) for the femoral neck. The study sample included 12 patients (mean age, 43.9 yr; mean height, 123.7 cm). Findings were compared with 10 osteopenic subjects without developmental abnormalities (mean age, 56 yr; mean height, 164.8 cm) and 10 healthy control subjects matched for sex and age to the LS patients (mean height, 165.5 cm). BMAD in the LS group was 0.201 +/- 0.02 g/cm(3) at the lumbar spine and 0.201 +/- 0.04 g/cm(3) at the femoral neck; corresponding values for the osteopenic group were 0.130 +/- 0.01 and 0.140 +/- 0.01 g/cm(3), and for the controls, 0.178 +/- 0.03 and 0.192 +/- 0.02 g/cm(3). Although areal BMD was significantly lower in the LS and osteopenic subjects compared with controls (P < 0.02) at both the lumbar spine and femoral neck, BMAD was low (P < 0.01) in the osteopenic group only. In conclusion, DEXA does not seem to be a reliable measure of osteoporosis in patients with LS.     

Falkor,a novel cell growth regulator isolated by a functional genetic screen

A novel cell growth regulator, named Falkor, was identified using a functional approach to mammalian gene cloning, the Genetic Supressor Elements (GSE) method. In this screen, expression of the C-terminal domain of Falkor conferred cells with resistance to cisplatin-induced growth arrest. Expression of the C-terminus of Falkor, but not of the full-length protein, enhanced cell growth both following genotoxic stress and under normal conditions suggesting a general role for this protein in cell growth control. This effect of the C-terminus fragment was abrogated by over-expression of the full-length Falkor, suggesting that the fragment counteracts the function of the full-length protein. Falkor is encoded by a 2-kb mRNA which is present at different levels in various tissues, and is localized in the nucleus of cells. The C-terminal domain of Falkor, isolated from the GSE library, has significant homology to a known human and rat cell growth regulator, SM-20, and to the C. elegans protein EGL-9, recently shown to modify the Hypoxia Inducible Factor-1alpha. The homology suggests that these proteins share a functional domain that is conserved among a family of growth regulation proteins.     

Apoptosis and cell proliferation capacity in AKR lymphoma malignancy variants

Dysregulation in apoptotic cell death has recently emerged as a factor in tumorigenesis, but its effect in tumor progression is not yet established. In the present study we evaluated the levels of proliferative and apoptotic cell fractions in a T-cell lymphoma tumor progression model. We compared these features and the expression of apoptosis-related genes in primary tumors of several AKR lymphoma malignancy variants. According to DNA flow cytometry, a considerable proportion of cells (35-40%) was in the proliferative (S + G₂/M) phase in all variants, but a slight augmentation with increasing malignancy was noted. Apoptotic cell content was, unexpectedly, the lowest in the less malignant variant. This might be due to the higher content in macrophages observed in this variant, which possibly partly eliminated apoptotic bodies. We found an increase in bcl-2 level with increasing malignancy that was probably counterbalanced by the simultaneous increase observed in the Fas receptor     

Fetal bone grafts do not elicit allograft rejection because of protecting anti-Ia alloantibodies. Implications to the immune survival of fetuses in allogeneic mothers.

In a previous study we showed that allografts of BN fetal bone, unlike allografts of adult bone, are not rejected by allogeneic recipients of the Lewis strain in spite of the existence of major histocompatibility complex (MHC) incompatibility between donors and hosts. In the present study, we analyzed the relationships existing between the host and fetal tissue that determine graft survival. We found that (1) the fetal BN graft, unlike adult grafts, induces in Lewis recipients a vigorous humoral response consisting mainly in the production of IgG antibody that seems to be directed against antigens of Ia-like specificities. (2) The BN rats are genetically defective in their capacity to respond to determinants and thus are not capable of producing anti-Ia antibodies; in accordance, Lewis fetal bone grafts are rejected by the BN recipients. (3) Chondrocytes isolated from fetal mouse bones do express Ia antigenic determinants. We suggest that the survival of an allogeneic fetal graft in an immunologically intact recipient depends on an active and selective immune response directed against the Ia components associated with the MHC on the embryonic and fetal cells. On the basis of these notions, we propose that the capacity of Ia determinants expressed on cells of the embryo, to elicit anti-Ia and IgG alloantibodies in the pregnant mother, determines the capacity of the embryo to escape rejection by the histoincompatible mother.     

Evidence for increased lysyl oxidase, the extracellular matrix-forming enzyme, in Alzheimer's disease brain

The study is based on the premise that the enzyme lysyl oxidase (LO), which catalyzes the crosslinking of extracellular matrix (ECM) proteins, participates in ECM modulation and senile plaque formation in Alzheimer's disease (AD). Experiments on hippocampal samples indicate that LO activity is increased (about 30%) in AD, but also in non-Alzheimer's dementia, as compared to controls with unrelated diseases. Immunohistochemistry with specific LO antibody indicates localization in blood vessel walls and in plaque-like structures. The number of LO-positive plaque-like structures in AD was over two-fold higher as compared to both non-Alzheimer's dementia and control groups. The findings lead us to suggest that active LO molecules in the ECM may be associated with plaque formation.     

Increased choline kinase activity in the rat superior cervical ganglion after axonal injury

The activity of choline kinase (CK) was examined in the rat superior cervical ganglion (SCG) during development and following postganglionic axotomy. The highest specific enzyme activity (nmol phosphorylcholine/mg protein/h)52±8, is observed 5 d before birth, then it rapidly decreases by about 50%, reaching at the day of birth levels observed in the ganglion throughout life. During development the total enzyme activity per ganglion is increased steadily until it reaches a 5-fold increase which parallels the increase in protein content. Following axotomy the enzyme activity per ganglion is rapidly increased by about 2-fold between 1 and 5 d postoperative and then gradually decreases reaching control levels at 30 d. The transient increase in enzyme activity parallels the increase in protein content of the axotomized ganglia. The peak increase in enzyme activity coincides with the peak chromatolytic response of the axotomized ganglion. We conclude that choline kinase activity is transiently increased within neurons after axonal injury, and that this event represents an effort of the nerve cell body to enhance its phosphatidylcholine biosynthesis essential for new membrane synthesis during the regeneration of the cut axon.     

Infection with a proposed new subspecies of Babesia canis, Babesia canis subsp. presentii, in domestic cats

Parasitemia with a large Babesia species was identified in two domestic cats from Israel. One cat, also coinfected with feline immunodeficiency virus and "Candidatus Mycoplasma haemominutum," had profound icterus and anemia which resolved after therapy, whereas a second cat was an asymptomatic carrier. Amplification and sequencing of the 18S rRNA gene, followed by phylogenetic analyses, indicated that infection was caused by Babesia canis. However, the sequences of the internal transcribed and 5.8S rRNA regions of the ribosomal operon used for subspeciation of B. canis were markedly different from the recognized subspecies of B. canis, which include B. canis vogeli, B. canis canis, and B. canis rossi. Based on phylogenetic comparisons of the 18S rRNA gene, 5.8S, and internal transcribed spacer sequences of the isolates from the cats and on the smaller sizes of the merozoite and trophozoite stages of this parasite, which distinguish it from the subspecies of B. canis present in dogs, we propose to identify the novel feline genotype of B. canis described in the present study as a new subspecies, B. canis subsp. presentii.