Rare carotid-vertebrobasilar anastomoses with notes on the differentiation between proatlantal and hypoglossal arteries

Suspected to be a syndrome rather than an authentic clinical entity, the "desquamative interstitial pneumonia" (DIP) exhibits typical anatomo-pathological aspects of intra-alveolar proliferation of granular pneumocytes, type II pneumocytes, leaving the alveolar interstitium unaffected. In absence of superinfection, it remains almost free of fibrous or inflammatory manifestations. The association of DIP to 4 other fundamental histological varieties of diseases of the pulmonary interstitium (UIP, BIP, LIP, GIP) is at the origin of Liebow's classification. The clinical individualization of these entities is still questioned.     

Evidence for an inhibition by endogenous galanin of neurogenic cutaneous vasodilatation in the pigeon

The effect of high affinity galanin antagonist M35 on neurogenic cutaneous vasodilatation has been studied in the pigeon using a Laser Doppler Imager. Cutaneous application of mustard oil or antidromic electrical stimulation of a cutaneous nerve produced a small increase in skin blood flow. Close arterial injection of M35 prior to chemical or electrical stimulation resulted in a marked augmentation of the vasodilatory response. This effect was abolished by chronic denervation. The results suggest a nerve-mediated inhibitory effect of endogenous galanin on neurogenic cutaneous vasodilatation in the pigeon skin and provide the first experimental evidence for an inhibitory local regulatory function of cutaneous sensory nerves at least in the avian skin.     

Frequency of ApoB and ApoE gene mutations as causes of hypobetalipoproteinemia in the framingham offspring population

Rearranged immunoglobulin variable genes are extensively mutated after stimulation of B lymphocytes by antigen. Mutations are likely generated by an error-prone DNA polymerase, and the mismatch repair pathway may process the mispairs. To examine the role of the MSH2 mismatch repair protein in hypermutation, Msh2-/- mice were immunized with oxazolone, and B cells were analyzed for mutation in their VkappaOx1 light chain genes. The frequency of mutation in the repair-deficient mice was similar to that in Msh2+/+ mice, showing that MSH2-dependent mismatch repair does not cause hypermutation. However, there was a striking bias for mutations to occur at germline G and C nucleotides. The results suggest that the hypermutation pathway frequently mutates G.C pairs, and a MSH2-dependent pathway preferentially corrects mismatches at G and C.     

An analysis of risk factors for withdrawal from dialysis before death

Withdrawal from dialysis has been a significant cause of mortality among dialysis patients, accounting for 6 to 22% of deaths. Since 1990, a new death notification form has allowed more detailed analyses of withdrawal from dialysis separate from causes of death. Using the U.S. Renal Data System data base, this study examined 116,829 deaths in adult patients from 1990 to 1995. Adjusted odds ratios were calculated for the risk of withdrawal using logistic regression. Adjustments included age at death, ethnicity, gender, cause of death, primary cause of end-stage renal disease, time on dialysis, and dialysis modality. In addition, odds ratios of withdrawal were calculated for deaths in patients who started dialysis after age 65. Death was preceded by withdrawal significantly more frequently in women than in men, more than twice as frequently in Caucasians than in African-Americans or Asians, and more frequently in older than in younger age groups. Patients who died of chronic diseases (e.g., dementia, malignancy) were much more likely to withdraw before death, whereas patients who died from more acute causes (e.g., coronary artery disease) were less likely to withdraw before death. It is concluded that patients who are Caucasian, female, older, or die of chronic or progressive diseases are more likely to withdraw from dialysis before death. The ethnic and gender differences in withdrawal do not appear to have a medical explanation from this analysis. Further research along sociologic lines is needed to better explain the differences in withdrawal from chronic dialysis.     

Associations of GAD65- and IA-2- autoantibodies with genetic risk markers in new-onset IDDM patients and their siblings. The Belgian Diabetes Registry

OBJECTIVE: To investigate the association of GAD (65-kDa) autoantibodies (GAD65-Abs) and IA-2 autoantibodies (IA-2-Abs) with human leukocyte antigen (HLA)-DQ and insulin gene (INS) risk markers in patients with recent-onset IDDM and their siblings. RESEARCH DESIGN AND METHODS: Blood was sampled from 608 recent-onset IDDM patients and 480 siblings, aged 0-39 years and consecutively recruited by the Belgian Diabetes Registry, to determine GAD65- and IA-2-Ab (radiobinding assay), HLA-DQ- (allele-specific oligonucleotyping), and INS-genotypes (restriction fragment length polymorphism analysis; siblings, n = 439). RESULTS: At the onset of IDDM, GAD65-Abs were preferentially associated with two populations at genetic risk but only in the 20- to 39-year age-group: 1) their prevalence was higher in carriers of DQA1*0301-DQB1*0302 (88 vs. 73% in non[DQA1*0301-DQB1*0302], P = 0.001), and 2) an association was found in patients lacking this haplotype but carrying DQA1*0501-DQB1*0201, together with INS I/I (87 vs. 54% vs. non[INS I/I], P = 0.003). Siblings of IDDM patients also presented the association of GAD65-Abs with DQA1*0301-DQB1*0302 (13 vs. 2% non[DQA1*0301-DQB1*0302], P < 0.001), while associations with the second genetic risk group could not yet be assessed. At the onset of IDDM, IA-2-Ab prevalence was higher in carriers of DQA1*0301-DQB1*0302 (69 vs. 39% non[DQA1*0301-DQB1*0302], P < 0.001) but not of DQA1*0501-DQB1*0201 or INS I/I. This association was present in both the 0- to 19- and the 20- to 39-year age-groups. It was also found in siblings of IDDM patients (4 vs. 0% non[DQA1*0301-DQB1*0302], P < 0.001). CONCLUSIONS: Both GAD65- and IA-2-Abs exhibit higher prevalences in presence of HLA-DQ- and/or INS-genetic risk markers. Their respective associations differ with age at clinical onset, suggesting a possible usefulness in the identification of subgroups in this heterogeneous disease.     

Identification of a prostate inhibitory substance in a pollen extract

Recently, much attention has focused on the treatment of BPH with the pollen extract, Cernilton. The present investigation was designed to identify the active component in this agent which might be responsible for the symptomatic relief of BPH as previously reported. Sequential purification of the active component present in the pollen extract was carried out by a combination of dialysis, gel filtration, and reverse phase chromatography. To monitor the biological activity of each of the purified fractions, a biological assay employing the human prostate cancer cell line DU145 was undertaken. While we have identified a number of constituent components in the pollen extract, only one fraction designated V-7 (FV-7) maintained a strong inhibitory effect on the growth of DU145 cells. The inhibition was time- and dose-dependent, and the concentrations of FV-7 required to reduce the cell numbers by 50% (IC50) after 2 days of exposure was 5 micrograms/ml. FV-7 was also inhibitory towards the primary culture of prostate stroma and epithelial cells, with the stroma/fibroblast showing greater sensitivity towards the HPLC-purified component. However, it should be noted that this inhibitory activity measured in the primary culture cells was only achieved at higher concentrations of FV-7. Preliminary characterization of the active ingredient identified FV-7 as DIBOA which is a cyclic hydroxamic acid. FV-7 and DIBOA induce similar inhibitory effects on the growth of DU145 cells.