Increased Ki-67 proliferative index and absence of P16INK4 in CIN-HPV related pathogenic pathways different from cervical squamous intraepithelial lesion

BACKGROUND/AIM: It is generally assumed that similar pathways are involved in human papillomavirus (HPV) induced pathogenesis of cervical squamous intraepithelial lesions (SILs) and cancers and a subset of conjunctival intraepithelial neoplasm (CIN)-that the malignancies or pre-cancerous lesions arise through HPV oncoproteins E6 and E7, which disrupt the pathways of p53 and the product of the retinoblastoma (Rb) gene and, in turn, increase the protein product of gene p16INK4 through the mechanism of positive feedback. Several cell cycle molecules are detected to test this hypothesis. METHODS: Nine cases of CIN and eight non-CIN cases were analysed for the expression of Ki-67, pRb, p53, and p16INK4 via immunohistochemistry. Nine cases of cervical high grade squamous intraepithelial lesion (HSIL), and 10 cases of cervical low grade squamous intraepithelial lesion (LSIL) were included for stain control of p16INK4a, and comparison of p16INK4a expression to CIN cases. A nested polymerase chain reaction and a genechip HPV typing were used to detect HPV infection and types in the CIN and non-CIN samples RESULTS: HPV positivity was demonstrated in all of the CIN lesions but in none of the non-CIN lesions. The Ki-67 proliferative index (Ki-67 PI) was statistically higher in the CIN group than the non-CIN group; however, there were no differences of expression of pRb and p53 between the two groups and no expression of p16INK4 in all cases. All nine cases of HSIL, and seven out of 10 cases of LSIL used for stain control were immunoreactive for p16INK4a. There were statistically significant differences in overexpression of p16INK4a between the CINs and SILs CONCLUSIONS: The Ki-67 proliferative index may be a sensitive marker for CIN lesions and these results, with significant differences in overexpression of p16INK4a between CINs and SILs, may provide new evidence that HPV related mucosal dysplasia in different anatomical locations may lead to dissimilar molecular pathways.     

The relationships between insulin resistance and components of metabolic syndrome in Taiwanese Asians

Metabolic syndrome (MetS) is a complicated clinicopathological entity with clustering of cardiovascular and metabolic risk factors, which includes central obesity, hypertension, dyslipidemia and glucose intolerance. There were many studies investigating a wide variety of clinical and pathophysiological aspects of this syndrome. However, the cutoffs of the components of MetS are not yet being evaluated by measured the insulin resistance (IR) directly. In this study, we enrolled 564 (male/female: 250/314) middle-aged healthy subjects. Each of the male and the female group was further divided into four subgroups (group 1 to group 4). Group 4 had the top 25 percentile of most severe IR determined by insulin suppression test. We then obtain the mean values of each component of the MetS in group 4 and compared them with the definitions of World Health Organization, National Cholesterol Education Program Adult Treatment Panel III, European Study Group of Insulin Resistance and International Diabetes Federation. The means of the blood pressure (BP) (male, 125/81; female, 125/80 mmHg) and the triglyceride (TG) (male, 1.6; female, 1.4 mmol/l) in group 4 were lower, and the fasting plasma glucose (6.2 mmol/l) was higher than the cutoffs of the other four sets of the criteria. The means of the high-density lipoprotein cholesterol (male, 0.9; female, 1.03 mmol/l) and the body mass index (male, 26.9; female 26.1 kg/m(2)) in group 4 were consistent with the cutoffs of other four groups and also the Taiwan Health Department criteria. In conclusion, we suggest to lower the cutoffs of the BP from 140/90 to 125/80 mmHg, TG from 1.7 to 1.6 mmol/l for males and 1.4 mmol/l for females for MetS definition, at least in Taiwan. This may help to early detect subjects under high risk of future coronary heart disease and diabetes. Still, these newly proposed cutoffs need larger-scale epidemiological studies to confirm.     

Topical anesthesia for out-patient adult cataract surgery without an anesthesiologist

To review the local anesthesia environment in France in adult out-patient cataract surgery. The author considers the presence or absence of an anesthesiologist in the operating room. The report shows that in many circumstances there is no need for an anesthesiologist if the following criteria are respected: the adult is fully informed, in rather good health, with no acute risk factors, and surgery is performed by a senior surgeon in a certified operating room. In France, a move toward more flexible regulations is expected, with a new cooperation between ophthalmologists and anesthesiologists that will lead to a new true risk/benefit/obligation ratio. Respect of the individual and safety remain crucial requirements making systematic generalizations impossible.     

An intermediate form of juvenile Paget's disease caused by a truncating TNFRSF11B mutation

Juvenile Paget's disease (JPD) is a rare condition with an autosomal recessive mode of inheritance. Typically presenting in infancy or early childhood, the disorder is characterized by a generalized widening of the long bones and thickening of the skull combined with sustained elevation of serum alkaline phosphatase levels. The extremely rapid bone turnover results in osteopenia, fractures, and progressive skeletal deformity. In 2002, mutations in TNFRSF11B, the gene encoding osteoprotegerin, were described as underlying JPD. We evaluated a patient with JPD at the clinical, biochemical, radiological, and molecular level. Mutation analysis of TNFRSF11B revealed a homozygous insertion/deletion in exon 5, predicted to result in truncation of the protein at amino acid 325. The residual activity of the mutated protein product was investigated by Western blotting and ELISA upon transient overexpression. Absence of the C-terminal domain abolished homodimerization and was shown to lead to a decreased capacity of the mutant protein to bind its ligand RANKL. We conclude that truncation of the C-terminal part of osteoprotegerin negatively affects functional activity. As a consequence, osteoclast formation and function are up-regulated, causing the increased bone turnover seen in this patient.     

New aspects of diabetes

Type II diabetes is a serious, insidious disease which is growing at an impressive rate, with 200 million diabetics worldwide and as many who ignore their state. Having been seriously studied over more than a century and a half, an enormous quantity of knowledge regarding this disease has been accumulated. The research we are conducting has allowed us to identify the most important actors responsible for diabetes. These are glucose which leads to glyoxal and to methylglyoxal which in turn reacts with innumerable targets in the organism (including insulin) unless prevented from doing so by detoxifying mechanisms (e.g., glyoxalases). The role of microorganisms in the occurrence and development of diabetes has also to be seriously examined.     

MMP-9 correlates with electrophysiologic abnormalities in Guillain-Barré syndrome

To investigate the role of MMP-9 in Guillain-Barré syndrome, the authors correlated electrophysiologic abnormalities and MMP-9 plasma levels in a series of 21 patients. MMP-9 plasma levels were higher in the demyelinating group than in the nondemyelinating group, and in patients with high CSF protein level. Increase of MMP-9 circulating levels correlated with the increase of F waves latencies, reduction of CMAP amplitude, and decrease of nerve conduction velocities. Circulating MMP-9 may contribute to the peripheral nerve dysfunction of demyelinating Guillain-Barré syndrome.     

Mitochondrial DNA polymorphism detected with the restriction enzymes BstNI and BclI in a French Canadian population

The enzymes Bst NI and Bell were used to detect various human mitochondrial DNA RFLPs in a sample of 104 unrelated French Canadians. These sequence variations were found in total white blood cell DNA probed with whole human mitochondrial DNA. With Bst NI, 6 mitochondrial DNA restriction patterns (morphs) were identified. Bst NI morphs 2–6 each differ from morph 1 by one single distinct restriction site gain or loss on the mitochondrial DNA molecule. Although Bst NI morph 1 was found in most of the subjects (80%), each other morph was observed at a frequency of at least 3%. With the enzyme BclI , 4 different morphs were detected. Morphs 2–4 also result from different single restriction site alteration as compared with Bcl I morph 1. The morph 1 was clearly the most frequent (95%) while morphs 3 and 4 were present in only 1% of the subjects. These data indicate that the enzyme Bst NI and, to a much lesser extent, the enzyme Bcl I detect mitochondrial Dn'A polymorphism in Caucasians. They are therefore of interest for population genetics studies.     

Polyhydroxylated C60, Fullerenol,a Novel Free-radical Trapper,Prevented Hydrogen Peroxide- and Cumene Hydroperoxide-elicited Changes in Rat Hippocampus In-vitro

The role of polyhydroxylated C₆₀ (fullerenol), a novel free-radical trapper, in prevention of hydrogen peroxide- and cumene hydroperoxide-elicited damage was studied in hippocampal slices from the rat in-vitro. The interactions of polyhydroxylated C₆₀, adenosine and 6,7-dinitroquinoxaline-2,3-dione (DNQX) were also compared. Hydrogen peroxide (0.006–0.02%) and cumene hydroperoxide (0.5–1.0 mm) both reversibly reduced the amplitudes of CA1-evoked population spikes in the hippocampal slices. Deferoxamine (1 mm) had little effect on the population spikes. Deferoxamine (1 mm) significantly prevented the hydrogen peroxide (0006%)-elicited inhibition of the population spikes. Polyhydroxylated C₆₀ (01 mm) significantly prevented hydrogen peroxide- or cumene hydroperoxide-elicited reduction of the population spikes and also prevented the effects of hydrogen peroxide and cumene hydroperoxide on paired-pulse facilitation in the hippocampal slice. Adenosine reduced the amplitude of population spikes and promoted paired-pulse facilitation in the CA1 region of the hippocampus. Polyhydroxylated C₆₀ did not alter either of the effects of adenosine on the population spikes. DNQX reduced the amplitude of the population spikes in the CA1 region but did not affect the ratio of paired-pulse facilitation. Fullerenol did not alter either effect of DNQX on the population spikes. These results suggested that polyhydroxylated C₆₀ prevented hydrogen peroxide- and cumene hydroperoxide-elicited damage in the hippocampus slices. These effects might be associated with the free-radical scavenging activity of polyhydroxylated C₆₀.     

Anti-HPA-4b (anti-Yuka) neonatal alloimmune thrombocytopenia: first report in a Caucasian family

Neonatal alloimmune thrombocytopenia (NAIT) is caused by platelet antigen incompatibility between the mother and fetus. NAIT is mainly due to alloimmunization; the frequency varying among ethnic groups. In Caucasians HPA-1a is the antigen most frequently implicated. In Japan, NAIT due to anti-HPA-4b antibody has already been described, but this is the first case to be reported in Caucasians.