Clinical Performance of Complete-Arch Implant- Supported Rehabilitations Using Monolithic Lithium Disilicate Restorations Bonded to CAD/CAM Titanium and Zirconia Frameworks up to 5 Years.

This clinical study evaluated the survival of monolithic lithium disilicate (ML) (IPS Emax, Ivoclar Vivadent) restorations bonded to complete-arch CAD/CAM made titanium or zirconia frameworks. Between August 2007 and December 2009, 15 patients (7 female, 8 male; mean age: 56.8 years old) received 30 implant-supported screw-retained rehabilitations with ML restorations cemented to CAD/CAM made titanium (T) (n=6) or zirconia (Z) frameworks (n=24) adhesively (Multilink Automix, RelyX Unicem) and followed up until December 2015. The evaluation protocol involved technical failures (chipping, debonding or fracture of crown/framework, screw loosening), Californian Dental Association (CDA) quality criteria (Romeo: Excellent; Sierra: Acceptable; Tango: Retrievable; Victor: Not acceptable) and biological failures (mucositis, peri-implantitis). Mean observation time was 60.3 months. No implants were lost, and all the prostheses were in situ. Four mechanical failures occurred in the form of minor chipping (n=3 in ML-Z, n=1 in ML-T) and major fracture in ML crown (n=1 in ML-Z). Romeo scores (N=370) decreased until final observation (N=347) and 23 Sierra scores were given to the restorations. Mucositis was observed in 3 patients and peri-implantitis in one patient. Complete-arch implant-borne FDPs made of monolithic lithium disilicate bonded to titanium or zirconia frameworks could be a promising alternative.

Reliability of Chair-side Monolithic CAD-CAM Generated Lithium Disilicate Single Crowns with Knife- Edge Finish Line: Up to 5-Year Retrospective Analysis of Clinical Performance.

This clinical study evaluated the survival of monolithic lithium disilicate (MLD) single crowns. Between January-2010 and January-2015, 87 patients received 122 MLD (IPS e.max CAD) single crowns on natural teeth with knife-edge finish lines that were adhesively bonded (Maxcem Elite). MLD single crowns (N=122) were bonded on 60 molars (maxilla:35, mandible:25), 53 premolars (maxilla:27, mandible:26), 4 canines (maxilla:2, mandible:2), 3 laterals and 2 centrals (maxilla). One crown fracture, one retention loss and one endodontic complication were experienced (survival rate: 97.5%). MLD single crowns could be safely indicated on teeth with knife-edge preparations.

Phytochemical fingerprint and chemometrics for natural food preparation pattern recognition: an innovative technique in food supplement quality control.

Recently, the fingerprint approach using chromatography has become one of the most effective tools for quality assessment of herbal medicines and food supplements: due to the complexity of the chromatographic fingerprint and the irreproducibility of chromatographic instruments and experimental conditions, chemometric approach is employed to deal with the chromatographic fingerprint. The study was aimed at developing new analytical methods for the multivariate phytochemical fingerprinting of bioactive compounds in eight tree-species bud-preparations, commonly used in phytotherapy. Methods was used to identify and quantify the main bioactive compounds (polyphenols, organic acids and vitamins), and obtain a specific botanical profile in order to assess the contribution of each single bioactive class to the total bud preparation phytocomplex. A chemometric approach was used to distinguish among different genotypes assuring the identity, safety and quality of the botanical raw materials. The established protocol was simple, sensitive and reliable and it could be used for the evaluation and quality control of bud-extracts and natural food supplements: the proposed method was successfully applied to the characterization of commercial bud-preparations, demonstrating to be an effective tool for the fingerprinting of this plant material. The new approach developed in this study represents a good alternative for improving the classification results of herbal materials with complex chromatograms. It should be necessary to develop a "multivariate chromatographic fingerprint", in order to differentiate the herbal preparations according to their genotype, avoiding substitutions, changes or adulterations with other species or synthetic drugs.

Botanicals in Ribes nigrum bud-preparations: an analytical fingerprinting to evaluate the bioactive contribution to total phytocomplex.

UNLABELLED: CONTEXT. Ribes nigrum L. (Grossulariaceae) is among the most commonly used herbal medicines and it is popularized for its alleged tonic effect and curative and restorative properties. The current practice of identifying herbal extracts is by measuring the concentration of the main botanicals. Their concentrations are used to characterize the herbal preparations and fingerprinting is recommended by the main Pharmacopeias as a potential and reliable strategy for the quality control of complex mixtures. OBJECTIVE: The aim of this research was to perform an analytical study of R. nigrum bud-preparations, in order to identify and quantify the main bioactive compounds, obtaining a specific chemical fingerprint to evaluate the single class contribution to herbal preparation phytocomplex. MATERIALS AND METHODS: The same analyses were performed using a high-performance liquid chromatograph-diode array detector both on University lab preparations and on commercial preparations from different Italian locations. Different chromatographic methods were used to analyse the macerated samples, two for polyphenols and one for terpenic compounds. RESULTS. Ribes nigrum was identified as a rich source of anti-inflammatory and antioxidant compounds. The observed analytical firgerprint demonstrated that these bud-preparations represent a rich source of terpenic and polyphenolic compounds, especially catechins and phenolic acids. DISCUSSION AND CONCLUSION: Analytical fingerprinting could be an important tool to study the assessment of chemical composition and bioactivities of plant-derived products, helping to find new sources of natural health-promoting compounds: this study allowed the development of an effective tool for quality control through botanical fingerprinting of bud preparations.

A combination therapy to treat second-degree anti-Ro/La-related congenital heart block: a strategy to avoid stable third-degree heart block?

While mainly based on the use of fluorinated steroids, there is no standard management of anti-Ro/La-related congenital heart block (CHB). This is a report concerning two consecutive cases of anti-Ro/La-related second-degree block treated with betamethasone (4 mg/day), weekly plasmapheresis, and intravenous immunoglobulins (IVIGs; 1 g/kg) administered every 15 days, a therapy that was begun shortly after CHB was detected and continued until delivery. The newborns were also treated with IVIG (1 g/kg) soon after birth and continued fortnightly until the anti-Ro/La antibody levels became undetectable. In both cases second-degree AV block reverted to a stable sinus rhythm with a first-degree atrioventricular (AV) block. Moreover, there was no recurrence of CHB when therapy was suspended, as confirmed by a 29 month and an eight month follow-up, respectively.

Polymerization degree and cementation methods of two different self-adhesive luting cements used for glass fiber postcementation.

AIM: Aim of this study was to evaluate two different luting cements and how their clinical procedures influence the postcementation quality. METHODS: Thirty-six freshly extracted mono-radicular teeth (N.=18) were treated endodontically and randomly divided into two groups. Posts were cemented respectively with two different self adhesive luting cements: Group A - RelyX Unicem (3M Espe) and Group B - Multilink Sprint (Ivoclar-Vivadent) following the manufacturers' instructions. Teeth were then thermocycled according to protocol ISO/TR 11405 and were immersed 24 hours in 2% methylene-blue solution. Each tooth was sectioned by a diamond-coated saw (Isomet-Buhler) from CEJ to apex. Each slice was examined for the presence or absence of gutta-percha remnants, voids, bubbles, dye infiltration degree and polymerization grade of the luting agent. Findings were evidenced by stereoscopic microscopy (30x) and Micro-Raman spectroscopy. Mann-Whitney and ANOVA statistical analyses were performed for all results. RESULTS: No statistical significances were evidenced for gutta-percha presence, dye infiltration and polymerization degree. Voids were present mostly in Group B and bubbles in Group A. Both differences were statistically significant. CONCLUSION: Materials and protocols for glass fiber posts cementation are fundamental for the clinical success. Self adhesive luting cements, if used correctly, could be an acceptable and quick luting agent for postcementation.

Evolution of echocardiographic and cardiac magnetic resonance imaging abnormalities during follow-up in patients with multisystem inflammatory syndrome in children.

AIMS: Multisystem inflammatory syndrome in children (MIS-C) with cardiovascular manifestations are frequent. However, there is lacking evidence regarding cardiological follow-up of this cohort of patients. The aim of our study was to describe the early and mid-term cardiac abnormalities assessed by standard and speckle-tracking echocardiography (STE), and cardiac MRI (CMR). METHODS AND RESULTS: We enrolled 32 patients (21 male, 11 female), mean age 8.25 ± 4years, with diagnosis of MIS-C. During admission, all children underwent TTE, STE with analysis of left ventricle global longitudinal strain (GLS) and CMR. Patients underwent cardiological evaluation at 2 (T1) and 6 months (T2) after discharge. Cardiac MRI was repeated at 6 months after discharge. Mean left ventricular ejection fraction (LVEF) at baseline was 58.8 ± 10% with 10 patients (31%) below 55%. Speckle-tracking echocardiography showed reduced mean LV GLS (-17.4 ± 4%). On CMR, late gadolinium enhancement (LGE) with non-ischaemic pattern was evident in 8 of 23 patients (35%). Follow-up data showed rapid improvement of LVEF at T1 (62.5 ± 7.5 vs. 58.8 ± 10.6%, P-value 0.044) with only three patients (10%) below ≤ 55% at T1. Left ventricular (LV) GLS remained impaired at T1 (-17.2 ± 2.7 vs.-17.4 ± 4, P-value 0.71) and significantly improved at T2 (-19 ± 2.6% vs. -17.4 ± 4%, P-value 0.009). LV GLS was impaired (>-18%) in 53% of patients at baseline and T1, whereas only 13% showed persistent LV GLS reduction at T2. Follow-up CMR showed LGE persistence in 33.4% of cases. CONCLUSION: Early cardiac involvement significantly improves during follow-up of MIS-C patients. However, subclinical myocardial dysfunction seems to be still detectable after 6 months of follow-up in a not negligible proportion of them.

Gut T cell-independent IgA responses to commensal bacteria require engagement of the TACI receptor on B cells.

The gut mounts secretory immunoglobulin A (SIgA) responses to commensal bacteria through nonredundant T cell-dependent (TD) and T cell-independent (TI) pathways that promote the establishment of mutualistic host-microbiota interactions. SIgAs from the TD pathway target penetrant bacteria, and their induction requires engagement of CD40 on B cells by CD40 ligand on T follicular helper cells. In contrast, SIgAs from the TI pathway bind a larger spectrum of bacteria, but the mechanism underpinning their production remains elusive. Here, we show that the intestinal TI pathway required CD40-independent B cell-activating signals from TACI, a receptor for the innate CD40 ligand-like factors BAFF and APRIL. TACI-induced SIgA responses targeted a fraction of the gut microbiota without shaping its overall composition. Of note, TACI was dispensable for TD induction of IgA in gut-associated lymphoid organs. Thus, BAFF/APRIL signals acting on TACI orchestrate commensal bacteria-specific SIgA responses through an intestinal TI program.

Indirect resin composite restorations: evaluation of polymerization of luting agents by means of micro-Raman spectrophotometry.

AIM: The degree of conversion of a luting composite cement influences its clinical performance. Aim of the study was to evaluate the degree of conversion of 4 different composite cements by means of micro Raman spectrophotometry. METHODS: Forty-four cylindrical onlays of different and defined thickness (1, 2, 3, 4 mm) were built using a custom made template. The onlays were made in composite material (Signum, Heraeus; shade A 3,5) and cemented onto a glass plate with different luting materials: dual curing (Variolink II, Calibra) and light curing (Venus flow, Tetric flow). The lamp tip was shielded in order to have the light reach the cement only through the onlay. Samples were divided into 12 groups (N.=3), differing in onlay thickness and luting material. Each sample was examined in three spots by a micro-Raman spectrophotometer (Dilor Hr-Labram). The conversion degree was evaluated by analyzing the variations in intensity of the 1638 cm(-1) aliphatic peak (C=C), characteristic of all Bis-GMA containing materials, related to the invariant 1608 cm(-1) (C-C of the aromatic ring). RESULTS: All materials show good polymerisation results below 1 mm and 2 mm onlays. Below onlays thicker than 3 mm a constant degree of conversion throughout the surface of samples could not be found: spots with satisfactory polymerisation and spots with insufficient polymerisation were found. CONCLUSIONS: Onlay thickness has a key role in cement conversion. The thicker the onlay, the less predictable the conversion.

B lymphocytes from patients with chronic lymphoproliferative disorders are equipped with different costimulatory molecules.

Several costimulatory molecules play a key role in the differentiation of B lymphocytes and in T-B-cell interactions. In this study, we addressed the question of whether different receptors and counter-receptors may be expressed on malignant B lymphocytes from chronic B-cell malignancies. Using flow cytometry and reverse transcription PCR analyses, the expression of molecules belonging to the tumor necrosis factor receptor (TNFR) and tumor necrosis factor ligand (TNFL) families, as well as the expression of CD80 and CD86 molecules, was analyzed in normal B cells and in different chronic lymphoproliferative disorders of B-cell type, including B-cell chronic lymphocytic leukemia (CLL), mantle cell lymphoma, hairy cell leukemia (HCL), and HCL variant. Different patterns of expression of TNFR and TNFL superfamily molecules were demonstrated among B-cell malignancies. In particular, CD40 was commonly observed on all B cells (both tumor and normal), whereas its ligand (CD40L), which is usually undetectable on resting normal B lymphocytes, was expressed in CLL and HCL but not in other chronic lymphoproliferative disorders. CD27 was not shown in normal B cells, although it was present in all malignancies and with particularly high density in mantle cell lymphoma. CD70 was widely distributed on tumor B lymphocytes, but not on the CD5+ normal counterpart. CD30 was strongly expressed in HCL variant and weakly in B-cell CLL, whereas its ligand showed a wide pattern of expression, including all neoplastic and normal B cells. TNFR II (CD120b) and CD80 were distributed on neoplastic B cells from all groups, usually at an intermediate to high degree of intensity, whereas the CD86 molecule was present at lower intensity than CD80. Finally, reverse transcription PCR analysis confirmed the presence of CD40L, CD30, and CD30L mRNAs in those B cells expressing the corresponding membrane-bound proteins at low density. Our data indicate that TNFR and TNFL molecules are of use clinically both in differentiating B-cell malignancies from the normal counterpart (i.e., CD27, CD70, CD40L, CD30, and CD80) and in defining different chronic B-cell disorders (i.e., CD40L, CD27, and CD30). Interestingly, the observation that several receptors and their ligands (i.e., CD40/CD40L, CD30/CD30L, and CD27/CD70) can be expressed on the same cell suggests that these molecules play a role in initiating and maintaining the neoplastic process by mediating B-T and B-B interactions.

Analysis of the T cell receptor in the lymphoproliferative disease of granular lymphocytes: superantigen activation of clonal CD3+ granular lymphocytes.

To investigate whether cell populations in CD3+ lymphoproliferative disease of granular lymphocytes (LDGLs) were skewed toward the use of specific V beta regions, we studied the repertoire of T-cell receptor (TCR) V beta gene products in 18 patients, as well as their relationship to the clonal bands in the Southern blot and the activation mediated by superantigens. Using a panel of monoclonal antibodies (mAbs) for conserved V beta segments and PCR, a dominant population expressing a specific V beta region was demonstrated in all patients. In five (27%) cases, granular lymphocytes (GLs) were found to express the V beta 13.1, while V beta 8 and V beta 6 were each expressed in three (17%) cases. The remaining cases were characterized by the proliferation of TCR V beta 2, V beta 3, V beta 4, V beta 9, V beta 12, V beta 16, and V beta 20. This finding indicates a biased usage of a limited TCR V beta in LDGLs, since nearly 60% of the cases utilized only three families of the TCR V beta genes. In all of the cases studied, we proved that the subset recognized by mAb and PCR was identical to that accounting for the extra band(s) of the Southern blot. This finding confirms the clonal nature of the population identified according to TCR V beta expression both by phenotype and PCR. On functional grounds, we evaluated whether GLs can be activated through the specific TCR using the superantigens recognizing discrete V beta families, such as staphylococcal proteins, including SEA, SEB, SEC1, SEC2, SED, and SEE. We demonstrated that the TCR-alpha/beta of clonal GLs in LDGL patients is functionally active in delivering cytotoxic and proliferative signals upon superantigen activation.

Serviceberry, a berry fruit with growing interest of industry: Physicochemical and quali-quantitative health-related compound characterisation.

Amelanchier canadensis (L.) Medik., commonly called serviceberry, is a potential functional food that is also used for its medicinal purposes. This work evaluated the potential of a cultivated serviceberry species as a functional food by characterising its physicochemical characteristics, antioxidant capacity, vitamin C, phenolics and other phytochemicals selected as health-promoting biomarkers, using high-performance liquid chromatography. The most important compound class identified was polyphenols (62.10%), followed by organic acids (22.63%), monoterpenes (7.95%), and vitamins (7.32%). Results showed that serviceberry fruits could be good sources of phenolic constituents, as catechins (343.46 ± 29.46 mg/100 gFW), anthocyanins (220.66 ± 17.43 mg/100 gFW), and tannins (209.29 ± 7.81 mg/100 gFW) (FW = fresh weight). These results highlight the potential role of A. canadensis fruits as a functional food. Further studies are needed to identify several genotypes for breeding to get suitable cultivars for fresh consumption and processing.

Responsive population dynamics and wide seeding into the duodenal lamina propria of transglutaminase-2-specific plasma cells in celiac disease.

A hallmark of celiac disease is autoantibodies to transglutaminase 2 (TG2). By visualizing TG2-specific antibodies by antigen staining of affected gut tissue, we identified TG2-specific plasma cells in the lamina propria as well as antibodies in the subepithelial layer, inside the epithelium, and at the brush border. The frequency of TG2-specific plasma cells were found not to correlate with serum antibody titers, suggesting that antibody production at other sites may contribute to serum antibody levels. Upon commencement of a gluten-free diet, the frequency of TG2-specific plasma cells in the lesion dropped dramatically within 6 months, yet some cells remained. The frequency of TG2-specific plasma cells in the celiac lesion is thus dynamically regulated in response to gluten exposure. Laser microdissection of plasma cell patches, followed by antibody gene sequencing, demonstrated that clonal cells were seeded in distinct areas of the mucosa. This was confirmed by immunoglobulin heavy chain repertoire analysis of plasma cells isolated from individual biopsies of two untreated patients, both for TG2-specific and non-TG2-specific cells. Our results shed new light on the processes underlying the B-cell response in celiac disease, and the approach of staining for antigen-specific antibodies should be applicable to other antibody-mediated diseases.

Alveolar macrophages as a cell source of cytokine hyperproduction in HIV-related interstitial lung disease.

Pulmonary macrophages play an important role in the pathogenesis of the acquired immunodeficiency syndrome (AIDS). They are known to be discrete target cells for human immunodeficiency virus (HIV), and compelling evidence is accumulating that alveolar macrophages (AMs) from HIV-infected patients behave as versatile secretory cells that, acting as antigen-presenting cells, release a great variety of cytokines. The secretory products of AMs, pivotal to their immune effects, may contribute to localized immune dysregulation as well as to primary lung damage and clinical disease. Pulmonary macrophages are also thought to facilitate retroviral spread by their direct infection, by presenting HIV antigens to uninfected T cells, and by secreting cytokines that transactivate HIV expression. This review briefly considers the events underlying the role of AMs in the pulmonary defense mechanisms against HIV and AIDS-related opportunistic infections. Following a brief overview of immune mechanisms taking place in the lungs of HIV-infected subjects, we describe the specific role of AMs in the immune mechanisms devoted to recognizing and removing HIV-infected cells and controlling the local growth of opportunists. The pathogenetic role envisaged for macrophages in lung damage are also reviewed in the context of the known biology of these cells. Finally, this review examines the relevance of the retroviral infection of AMs in terms of pathogenesis of the HIV-related interstitial lung disease.

The success of indirect restorations in posterior teeth: a systematic review of the literature.

AIM: Aim of the study was to evaluate the long-term reliability and effectiveness of inlays and onlays in ceramic and composite material, examining scientific studies published from 2004 to 2013. The results of this review were analyzed and compared with the important literature review proposed by Manhart in 2004. METHODS: With this review it was possible to analyze a total sample of 5858 Class I and II restorations, made in the posterior region: 5295 ceramic and 563 composite restorations in 2377 patients. Works were evaluated using USPHS, modified USPHS and CDA criteria after a mean observation period of 5.4 years (5.9 years for ceramic restorations, 2.6 for composite restorations). RESULTS: The arithmetic average of success was 94%, higher in ceramic restorations (94.9%) than composite materials (91.1%). The weighted average success rate was 95.3%, 92.8% for composite restorations and 96.3% for ceramic ones. The highest rates of success were found in ceramic restorations notwithstanding the longer observation period. CONCLUSION: Indirect restorations have a low failure rate and they prove to be an excellent choice in the treatment of both class I and II lesions. During the last 6 years, the parameters related to these restorations have improved, with a 4% increase of success.

Skewing of the T-cell receptor repertoire in the lung of patients with HIV-1 infection.

OBJECTIVES: A bias of the use of T-cell receptor (TCR) V beta regions has been reported both in peripheral blood and in several tissues in patients with AIDS, including lymph nodes, spleen and salivary glands. Although the disease is frequently characterized by an infiltration of T cells in the lung interstitium, no information is presently available on the configuration of the TCR repertoire in this microenvironment. This study was performed to address the question of whether a bias in T-cell selection occurs in the lung of patients with AIDS. METHODS: TCR beta-chain variable region (TCR-V beta) repertoire was analysed by flow cytometry and polymerase chain reaction (PCR) analyses in blood and lung lymphocytes of 13 patients with HIV-1 infection at different stages of the disease. Blood and lung lymphocytes were also assessed for their responsiveness to different superantigenic stimuli represented by staphylococcal enterotoxins (SEA, SEB, SEC1, SEC2, SED and SEE). RESULTS: Flow cytometry analysis in AIDS patients demonstrated an overexpression of cells bearing V beta 2 and V beta 3 gene segments in the lung compared with peripheral blood of the same subjects, as well as to lung and blood lymphocytes of normal controls. PCR analysis performed in AIDS patients extended these observations and demonstrated a significant bias also in the use of T cells bearing V beta 7 and V beta 9 gene regions in the lung compartment with respect to the blood. Virtually all T cells bearing the overrepresented V beta segment belong to the CD8 subset. Interestingly, T-lymphocyte response to different superantigens demonstrated a low proliferative rate in the lung with respect to the blood in HIV-1-infected patients. CONCLUSIONS: These findings indicate a compartmentalization of cells bearing discrete V beta gene products in the pulmonary microenvironment of patients with AIDS and suggest that the expansion of specific-V beta region subsets occurring in the lung might result from triggering by a superantigen.

Vascular network changes in the retina with age and hypertension.

OBJECTIVE: To compare retinal arterial bifurcation geometry in normotensive and hypertensive subjects. DESIGN: A retrospective observational study. METHODS: Fluorescein angiograms of normotensive (n = 13) and hypertensive (n = 12) subjects aged 30-80 years with uni-ocular retinal pathology were compared. Quantification of diameters of the parent, larger daughter and smaller daughter vessels (d0, d1 and d2, respectively) and of bifurcation angles (the angle between the two daughter arterioles, omega) of arteriolar bifurcations was performed from digitized retinal angiograms of the uninvolved eye. The relative diameters of parent and daughter vessels at bifurcations were summarized by junction exponents (x) such that d1x + d2x = d0x. RESULTS: Junction exponents were similar for normotensives and hypertensives (means +/- SEM, 2.65 +/- 0.18 and 2.48 +/- 0.17), but analysis of covariance showed a parallel decrease in x in the two groups with age. A positive association was found between x and arteriolar microvascular density. Bifurcation angles were more acute in hypertensives (74 +/- 3 degrees) than in normotensives (84 +/- 3 degrees) and declined with increasing age in both groups. CONCLUSIONS: The present findings indicate that ageing and possibly hypertension are associated with disadvantageous branching geometry in the human retinal vasculature, implying increased power costs of blood transport, uneven distribution of shear forces throughout the vascular tree and microvascular rarefaction. The present findings may have important implications for our understanding of the pathogenesis of vascular disease in ageing and hypertension and offer the prospect of a novel sensitive diagnostic approach to the cardiovascular system.

Retinal vascular network architecture in low-birth-weight men.

BACKGROUND: Low birth weight is associated with hypertension and increased cardiovascular mortality, but the mechanism of this association is not known. Hypertension is accompanied by abnormalities of the microvasculature including rarefaction. OBJECTIVE: To test the hypothesis that low birth weight is associated with an alteration in microvascular architecture. DESIGN: A stratified random sample of 100 men aged 64-74 years was selected from a cohort of men whose birth weights were known. They were of relatively high or low birth weight ('high' > or = 3700 g, 'low' < or = 3200 g) and high or low systolic blood pressure (high > or = 160 mmHg, low < or = 140 mmHg). METHODS: Retinal arteriolar geometry was defined in terms of arteriolar bifurcation angles and junction exponents (a measure of the relative diameters of parent and daughter vessels), measured from photographic diapositives using operator-directed image analysis. RESULTS: Members of low-birth-weight groups had significantly narrower bifurcation angles than did members of high-birth-weight groups (74 +/- 1 degree versus 78 +/- 1 degree, P= 0.017 by analysis of variance). There was no significant difference between angles in members of groups with high and low blood pressures. Neither birth weight nor blood pressure grouping affected junction exponents. CONCLUSIONS: Narrower bifurcation angles are associated with increased circulatory energy costs and may be related to a lower than normal microvascular density. Our finding of differences in retinal microvascular architecture might reflect a persistent alteration in vascular architecture as a result of an impairment of foetal development and could provide a mechanistic link between low birth weight and subsequently increased cardiovascular risk.

Ongoing hypermutation in the Ig V(D)J gene segments and c-myc proto-oncogene of an AIDS lymphoma segregates with neoplastic B cells at different sites: implications for clonal evolution.

To investigate the role of somatic Ig hypermutation in the evolution of AIDS-associated B cell lymphomas, we analyzed the Ig V(D)J and c-myc genes expressed by neoplastic B cells in two extranodal sites, testis and orbit, and clonally related cells in the bone marrow. Testis and orbit B cells expressed differentially mutated but collinear V(H)DJ(H), V kappa J kappa and c-myc gene sequences. Shared mutations accounted for 10.2%, 8.4%, and 4.3% of the overall V(H)DJ(H), V kappa J kappa, and c-myc gene sequences. Tumor-site specific V(H)DJ(H), V kappa J kappa, and c-myc mutations were comparable in frequency, and a single point-mutation gave rise to an EcoRI site in the testis c-myc DNA. Both shared and tumor site-specific V(H)DJ(H), V kappa J kappa, and c-myc mutations displayed predominance of transitions over transversions. The "neoplastic" V(H)DJ(H) sequence was expressed by about 10(-5) cells in the bone marrow, and contained two of the three orbital, but none of the testicular V(H)DJ(H) mutations. The nature and distribution of the Ig V(D)J mutations found in the kappa chain suggested a selection by antigen in testis and orbit. Our data suggest that, in AIDS-associated B cell lymphomas, the Ig hypermutation machinery targets V(H)DJ(H), V kappa J kappa, and c-myc genes with comparable efficiency and modalities.