Nuclear DNA polymorphism in a Mandenka population from Senegal: Comparison with eight other human populations

A large and ethnically well defined Mandenka sample from Senegal is analysed for 80 nuclear DNA RFLPs, and compared with eight previously studied human populations. A high level of genetic diversity is found in this sample, comparable to that observed in two African Pygmy samples, but lower than that of a European sample. High population variation is observed for most markers. A neutrality test reveals that the markers used in this study can be considered as neutral. A high correlation is found between genetic and geographic distances (r= 0·62), suggesting that geography does also affect long range population genetic relationships and is an important factor behind differentiation among human populations.     

Comparison of IL10 and IL2 genotypes of Turkish population with other populations

The human genome has been shaped by evolutionary and historical forces. Therefore, genetic polymorphisms are useful tools not only to understand the susceptibility to disease in modern populations, but the history of ancestral populations as well. For this purpose, data on genetic polymorphisms such as human leucocyte antigen, mitochondrial DNA sequence variability and the frequencies of TAP1 and TAP2 gene variants in Turkey have been reported previously. Here we have used interleukin (IL)‐10 (?592C/A, ?819T/C, ?1082G/A) and IL‐2 (?330T/G) as genetic markers to study the relationship between Turkish population and other populations.     

Comparison of head circumference in an Israeli child population with United States and British standards

The head circumference (HC) growth pattern of infants from 1 to 24 months of age was studied in a Jerusalem community. The means of HC of the study population are smaller for each age and sex group than those of the National Center of Health Statistics, USA reference population, London children and the Nellhaus standard. The regression of HC on length explains about 20% of the variance. In an analysis of variance controlling for social class, birth order and length, the differences by region of origin of the mother were not significant. The smaller HC of the study population is probably due to these children being shorter and lighter than the above-mentioned western populations. Malnutrition as a factor for small HC was excluded.     

Evaluation of skeletal tissue repair,Part 2: Enhancement of skeletal tissue repair through dual-growth-factor-releasing hydrogels within an ex vivo chick femur defect model

There is an unmet need for improved, effective tissue engineering strategies to replace or repair bone damaged through disease or injury. Recent research has focused on developing biomaterial scaffolds capable of spatially and temporally releasing combinations of bioactive growth factors, rather than individual molecules, to recapitulate repair pathways present in vivo. We have developed an ex vivo embryonic chick femur critical size defect model and applied the model in the study of novel extracellular matrix (ECM) hydrogel scaffolds containing spatio-temporal combinatorial growth factor-releasing microparticles and skeletal stem cells for bone regeneration. Alginate/bovine bone ECM (bECM) hydrogels combined with poly(d,l-lactic-co-glycolic acid) (P_DLLGA)/triblock copolymer (10–30% P_DLLGA–PEG–PL_DLGA) microparticles releasing dual combinations of vascular endothelial growth factor (VEGF), chondrogenic transforming growth factor beta 3 (TGF-β3) and the bone morphogenetic protein BMP2, with human adult Stro-1 + bone marrow stromal cells (HBMSCs), were placed into 2 mm central segmental defects in embryonic day 11 chick femurs and organotypically cultured. Hydrogels loaded with VEGF combinations induced host cell migration and type I collagen deposition. Combinations of TGF-β3/BMP2, particularly with Stro-1 + HBMSCs, induced significant formation of structured bone matrix, evidenced by increased Sirius red-stained matrix together with collagen expression demonstrating birefringent alignment within hydrogels. This study demonstrates the successful use of the chick femur organotypic culture system as a high-throughput test model for scaffold/cell/growth factor therapies in regenerative medicine. Temporal release of dual growth factors, combined with enriched Stro-1 + HBMSCs, improved the formation of a highly structured bone matrix compared to single release modalities. These studies highlight the potential of a unique alginate/bECM hydrogel dual growth factor release platform for bone repair.     

Gastric parietal cell carcinoma with an unusual, lymphoma-like histologic appearance: report of a case

We report a case of gastric carcinoma with an unusual histologic appearance and type of cellular differentiation. The tumor was resected from an 85-yr-old man who presented with epigastric pain and monoclonal gammopathy. The tumor was antral in location and transmurally infiltrated the stomach wall. Histologically, the tumor closely resembled a lymphoma with diffuse poorly cohesive sheets of tumor cells interspersed with histiocytes. Immunohistochemical study, however, clearly demonstrated the epithelial nature of this tumor. Electron microscopy also revealed evidence of epithelial differentiation and features of parietal cell differentiation. In this report, we describe the light and electron microscopic findings, immunohistochemical staining properties, and DNA flow cytometric findings of this tumor and briefly review the literature on parietal cell carcinomas.     

Patterns of failure with time of an artificial scaffold class ligament used for reconstruction of the human anterior cruciate ligament

A composite carbon fibre polyester scaffold class ligament (ABC — Active Biosynthetic Composite Ligament, Surgicraft Ltd., Redditch) has been used for primary reconstruction of the torn anterior cruciate ligament at Mayday University Hospital since 1985. A cohort of patients followed up until 1996 showed a high incidence of early failure of the implant due to rupture and stretching. This led to a detailed mode of failure analysis and as a result the surgical technique was modified and new instrumentation was introduced in 1992 leading to a substantial improvement in early and mid-term survivorship. However, from 1996 onwards a large number of patients was lost to follow-up and therefore in 2000 a second cohort of patients was recalled for retrospective review. All the patients in this cohort had undergone surgery after 1992 and following the introduction of new instrumentation and alteration in surgical technique. Review of the results in the second cohort showed a very low initial failure rate (0% in the first 3 years), but with an increasing incidence of failure (27.9%) noted between 5 and 7 years post-operatively.     

Comparison of sample units for estimating population abundance and rates of change of adult horn fly (Diptera: Muscidae)

This study compared the reliability of population estimates of adult horn fly, Haematobia irritans (L.), obtained using different sample units. Mean-variance relationships were similar for abundance estimates obtained by counting flies on the sunny sides of cattle, on the upper body, and on the whole animal. Precision varied among the sample units, and was lowest for estimates obtained using the sunny side. Abundance estimates obtained using the sunny side and upper body sample units were related to estimates obtained using the whole body sample unit. However, the proportion of flies in the upper body and sunny side sample units declined with increasing fly density. Seasonal movement toward the belly accounted for this decline. This movement resulted in bias in estimating rates of change based on counting flies on the sunny side and upper body sample units. Rates of change based on sampling the sunny side were more biased than estimates based on the upper body sampling unit. Bias in estimating rates of change was examined using an analytical model compared with field data, and resulted from changes in the proportion of flies occupying the sample unit. Bias also increased with increasing actual rates of change. The implication of these findings for studying horn fly populations are discussed.     

Apolipoprotein E polymorphism in Italy investigated in native plasma by a simple polyacrylamide gel isoelectric focusing technique. Comparison with frequency data of other European populations

A new polyacrylamide gel isoelectric focusing (PAGIEF) technique has been developed that allows rapid and reliable identification of Apolipoprotein E (APOE) phenotypes directly from plasma or serum without any prior treatment.
This method was used to determine the APOE phenotypes in samples from Central and Southern Italy, Sicily, and Sardinia. The frequencies observed for the APOE*2, APOE*3 , and AP0E*4 alleles in Central and Southern Italy (Sicily included) were similar (0·066, 0·851, 0·083 and 0·056, 0·858, 0·085 respectively) though lower APOE*4 frequencies were found in the more southern regions. The Sardinian population showed APOE gene frequencies (APOE*2 = 0·050, APOE*3 = 0·898, AP0E*4 = 0·052) to be significantly different from those of the rest of Italy owing to the low AP0E*4 frequency, the lowest among Caucasian populations. The frequencies were compared with those found in other European populations. A clear cut North-South decreasing cline was found for APOE*4 allele frequencies and an opposite trend was found for AP0E*3 frequencies. The overall dispersion of European populations as determined by the three APOE allele frequencies was graphically represented using coordinate analysis. The tendency of the APOE*4 frequency to decline with latitude both at the Italian and at the European level was discussed with reference to similar trends observed for dietary habits (saturated fat intake).     

Patterns of adherence with antiretroviral medications: an examination of between-medication differences.

OBJECTIVE: To determine whether adherence with one antiretroviral medication reliably predicts adherence with other antiretroviral medications. DESIGN: Cross-sectional repeated-measurement analysis. SETTING: Cohort study enrolling patients from Massachusetts and Rhode Island. PATIENTS: Total of 454 patients using antiretroviral medications for HIV infection. METHODS: For each antiretroviral medication, we asked patients to report how many days in the last week they had 1) missed a dose of the medication and 2) been off schedule with a dose of the medication. The reliability coefficient was used to compare between-person variance in adherence rates with total variance, which is the sum of between-person and within-person variance. RESULTS: The mean age of patients was 42 years; 28% were women and 37% were nonwhite. Sixty-six percent of patients were on three or more antiretroviral medications. Perfect adherence was reported by 42% of patients, and patients reported missing a dose on a mean of 1.5 days per week for each antiretroviral medication currently being taken. The reliability coefficient for days in the last week that the medication was missed was 0.85 (95% confidence interval [CI]: 0.83-0.87), and for days off-schedule in the last week, it was 0.88 (CI: 0.86-0.89). CONCLUSIONS: Most of the variability in antiretroviral adherence in this study was accounted for by between-patient differences in overall adherence rather than by within-patient differences in adherence patterns across medications. These data support the theory that when patients skip or are off schedule with doses, they skip or are off schedule with all the antiretroviral medications taken at that time. In the course of exploring patients' adherence issues, clinicians may find it useful to inquire about problematic dosing times. Researchers assessing adherence may not need to separately monitor adherence with each antiretroviral medication in a regimen.     

Cytologic indicators of condylomatous lesions of the uterine cervix with histologic correlation: an outpatient laboratory's experience

Human papillomavirus (HPV) is widely implicated as a primary etiologic factor in cervical carcinoma. Cytology plays an important role as the initial screening tool in the early detection of cervical lesions with koilocytotic features. The purpose of this study was to describe the various cytologic indicators of condylomatous lesions of the uterine cervix with histologic correlation. Cervical smears and biopsy specimens from 278 women seen in an outpatient clinical setting between January 1, 1985; and January 1, 1987, were reviewed. The histologic categories consisted of (1) flat condylomas with minimal cellular atypia; and (2) cervical intraepithelial neoplasia (CIN), I, II, or III with atypical koilocytosis. Cytologically in 57 cases, flat condylomas were composed predominantly of koilocytes containing large perinuclear halos and dyskeratotic cells. In the 221 cases of CIN with atypical koilocytosis, the cervical smears were composed predominantly of atypical koilocytes with large hyperchromatic nuclei and small perinuclear halos; a variable number of koilocytes with large perinuclear halos; pleomorphic dyskeratotic cells; and abnormal multinucleated cells. Mild, moderate, or severely dysplastic/carcinoma-in-situ cells (CIS) were also present. An understanding of the cytologic features associated with condylomatous lesions of the cervix will enable the cytopathologist to alert the clinician of the need to perform colposcopy with the appropriate follow-up treatment.     

PMMA-based bioactive cement: effect of CaF2 on osteoconductivity and histological change with time

A new bioactive bone cement (designated GBC), which is a polymethyl methacrylate- (PMMA-) based composite consisting of bioactive glass beads as an inorganic filler and high-molecular-weight PMMA (hPMMA) as an organic matrix, has been developed. The bioactive glass beads consist of MgO-CaO-SiO(2)-P(2)O(5)-CaF(2) glass. The purpose of the present study was to evaluate the effect of CaF(2) on osteoconductivity and to evaluate the degree of cement degradation with time. Three different types of cement were prepared. GBC(F +), which has been previously described, consisted of CaF(2)-containing bioactive glass beads and hPMMA. GBC(F -) consisted of CaF(2)-free bioactive glass beads and hPMMA. The third cement was hPMMA itself (as a reference material). These three types of cement were packed into the intramedullary canals of rat tibiae to evaluate osteoconductivity, as determined by an affinity index calculated as the length of bone in direct contact with the cement surface expressed as a percentage of the total length of the cement surface. Rats were killed at 4, 8, 25, and 52 weeks after implantation, and the affinity index was calculated for each type of cement at each time point. Histologically, new bone had formed along the surface of both GBC(F +) and GBC(F -) within 4 weeks, whereas hPMMA had little contact with bone, and an intervening soft tissue layer between bone and cement was detected. No significant difference in affinity index was found between GBC(F +) and GBC(F -) at any of the time points studied, although GBC(F -) showed higher affinity indices than GBC(F +) at 8, 25, and 52 weeks. The affinity indices for GBC(F +) and GBC(F -) were significantly higher than those for hPMMA at all time points. With GBC(F +) and GBC(F -), significant increases in the affinity indices were found as the implantation period increased, and the affinity index values at 52 weeks reached more than 70%. In hPMMA, no significant increase in affinity index was observed up to 52 weeks, and the value at 52 weeks was less than 30%. Although no significant difference in affinity index was found between GBC(F +) and GBC(F -), GBC(F -) is conclusively better than GBC(F +) because diseases such as chronic fluorosis might be caused by CaF(2)-containing glass beads. Regarding the cement degradation of both GBC(F +) and GBC(F -), the degree of the degradation at 25 weeks was the same as that at 52 weeks. Therefore, the cement degradation does not appear to proceed rapidly. Further studies are needed to better understand the degradation process.     

History of modern psychopharmacology: a personal view with an emphasis on antidepressants.

OBJECTIVE: This article provides the chemical basis for the molecular modification of H1 antihistamines in the rational development of some antidepressant and antipsychotic drugs. METHODS: A review of the literature and personal experiences have been compiled. CONCLUSIONS: The contributions of many basic scientists, the crucial observations of clinicians, and the desire of the drug industry to make money have resulted in the currently available psychopharmacological treatments. The future development of psychopharmacology depends on better clinical research to generate new hypotheses of the chemical and behavioral pathology of mental disease. Psychosomatic medicine can make a unique contribution in its interdisciplinary role of stressing brain, body, and mind relationships.     

PMMA-based bioactive cement: effect of glass bead filler content and histological change with time.

A new bioactive bone cement (designated GBC), which is a polymethyl methacrylate (PMMA)-based composite consisting of bioactive glass beads as an inorganic filler and high molecular-weight PMMA as an organic matrix, has been developed. The purpose of the present study was to evaluate the effect of the filler content on the mechanical properties and osteoconductivity of GBC, to decide the most suitable filler proportion, and to evaluate the degree of cement degradation with time. The bioactive beads, consisting of MgO-CaO-SiO(2)-P(2)O(5)-CaF(2) glass, were added to the cement in various proportions (40-70 wt %). The bending strength of GBC did not differ among the proportions (approximately 136 MPa), but the elastic modulus of bending of GBC increased as the glass bead filler content increased (approximately 4.1-7.2 GPa). The all types of GBC were packed into the intramedullary canals of rat tibiae to evaluate osteoconductivity, as determined by an affinity index calculated as the length of bone in direct contact with the cement surface expressed as a percentage of the total length of the cement surface. Rats were sacrificed at 4, 8, 25, and 39 weeks after implantation, and the affinity index was calculated for each type of GBC at each time point. Histologically, new bone had formed along the surface of all types of GBC within 4 weeks, even in GBC containing only 40 wt % of glass beads. The affinity indices of GBC tended to increase as the proportion of glass bead filler increased and as the implantation period increased. In GBC containing 60 or 70 wt % of glass beads, significant rapid increases in the affinity indices were found from 4 to 8 weeks, and the high values (approximately 70%) were maintained up to 39 weeks. A sign of glass bead degradation was observed at the bone-cement interface in the rat tibiae at 39 weeks. We conclude that, when mechanical properties and osteoconductivity are both taken into consideration, GBC containing 60 or 70 wt % of glass beads is the most suitable formulation, but that further studies are needed to investigate and overcome the degradation.     

Distribution of KIR genes in Han population in Yunnan Province: comparison with other Han populations in China

Killer cell immunoglobulin‐like receptors (KIRs) show extensive variation among different populations. In this study, 404 unrelated individuals in Han population in Yunnan Province, China, were genotyped for the presence or the absence of 16 KIR genes using the multiplex PCR‐SSP method. Our data showed that the inhibitory gene frequency of genes KIR2DL1, KIR2DL3, KIR3DL1, KIR2DL5 and KIR2DL2 was 0.930, 0.889, 0.789, 0.206 and 0.095, respectively, and the activating gene frequency of KIR2DS4, KIR3DS1, KIR2DS1, KIR2DS5, KIR2DS2 and KIR2DS3 was 0.795, 0.218, 0.196, 0.165, 0.095 and 0.087, respectively. In all, 44 distinct KIR genotypes were identified; genotype 1 was predominant with a frequency of 0.478, followed by genotypes 2 and 8 with a frequency of 0.121 and 0.077, respectively. Haplotype A outnumbered haplotype B by 2.39:1. In addition, phylogenetic tree and multidimensional scaling analysis (MDS) based on KIR genes in populations including Asian, African and Caucasians have been performed. Neighbour‐joining tree analysis and the MDS plot showed that Han populations were clustered together with Asian and were separate from other populations. The Han populations in China were separated into northern and southern groups; the Yunnan Han population investigated in this study was clustered in the southern group. These results implied that the difference between northern and southern Han populations might reflect responses to a variety of locally acting epidemiological challenges.     

G2 rotavirus infections in an infantile population of the South of Italy: variability of viral strains over time

Rotavirus positive samples collected in Palermo, Italy, during 2002-2004 did not react with the G2 type-specific RV5:3 monoclonal antibodies (MAbs) and could be identified as G2 only by RT-PCR genotyping. The genetic variation of VP7 and VP4 antigenic proteins was studied in 14 G2 samples including a selection of both those successfully characterized by serotyping and those failing to be serotyped. The phylogenetic analysis performed on partial VP7 sequences showed a temporal clustering of these strains, with those isolated in Palermo in 2003 belonging to the same lineage of G2 MAbs-unreactive strains identified in UK in 1996-1997 and in Bari, Italy, in 2003-2004. A single amino acid substitution in VP7 antigenic region A, at position 96 (Asp-->Asn), was consistently associated with the loss of antigenic reactivity. Five of the G2 strains were further characterized by sequencing of VP4-encoding genes as belonging to the P[4] type, and separate lineages clustering the strains according to a temporal distribution could be described. VP7 and VP4 antigenic proteins analysis provided evidence that over the last 11 years, at least two different populations of G2P[4] rotavirus strains have been infecting the infant population in Palermo. Considering the role of anti-VP7 and anti-VP4 neutralizing antibodies in rotavirus immunity, the emergence of new VP7-VP4 gene combinations might influence rotavirus circulation in the infant population and should be taken into consideration when devising vaccination strategies.     

Patterns of antibodies against latent and lytic antigens of human herpesvirus 8 in an endemic population and patients with Kaposi's sarcoma in Mozambique

The patterns of antibodies against latent and lytic antigens of human herpesvirus 8 (HHV‐8) were assessed using immunofluorescence assays of samples from 155 persons seropositive for HHV‐8 seen at public health centers and 24 patients with Kaposi's sarcoma (KS) from Mozambique. Of the 155 persons without KS, 48 (31%) had antibodies against latent antigens only, 29 (18.7%) had antibodies against lytic antigens only, and 78 (50.3%) had antibodies against both types of antigen. The HHV‐8 antibody titer tended to increase with age until age 40, after which it began to decrease. High titers of antibodies against latent and lytic antigens of HHV‐8 were detected mostly in persons co‐infected with HIV, and these increased titers could have a predictive value. All patients with KS except four patients who were seronegative for HHV‐8 had elevated titers of HHV‐8 antibodies, predominantly against latent antigens. The data suggest the potential for an increase in the development of KS in this endemic area for HHV‐8. J. Med. Virol. 82:1576–1581, 2010. © 2010 Wiley‐Liss, Inc.     

Rotavirus genotyping: keeping up with an evolving population of human rotaviruses.

The use of molecular methods for rotavirus characterisation provides not only increased sensitivity for typing, but also allows accurate and more complete characterisation of strains, and the identification of putative reassortant strains. However, due to the constant accumulation of point mutations through genetic drift, and to the emergence of novel genotypes, possibly zoonotic transmission and subsequent reassortment, the reagents and methods used require close monitoring and updating. Methods and oligonucleotide primers are described to overcome failures to type G9, G10 and P[11] rotavirus strains, and cross-reactivity identified between G10 and G3 rotaviruses.