Nutrient displacement associated with walnut supplementation in men.

BACKGROUND: Dietary guidance issued by various global government agencies recommends nut consumption within the context of a healthy-eating pattern. Nuts are nutrient dense and may promote nutrient adequacy. As an energy-dense food, nuts must replace other foods in the diet to prevent an excess of calories. METHODS: We evaluated how recommending the inclusion of walnuts (75 g day(-1) ) in the diet affected energy and nutrient intake in men (45-75 years; mean body mass index = 27.6 kg m(-2) ; n = 19) at risk for developing prostate cancer. Guidance was provided about incorporating walnuts isocalorically in a healthy diet. Three-day food records and body weight were collected at baseline and after two 8-week diet periods (usual versus walnut supplement diets). RESULTS: Energy intake on the walnut supplement diet exceeded the usual diet, although body weight was maintained. Energy intake was lower on the actual walnut supplement diet than the calculated walnut diet [10,865 kJ (2595 kcal) versus 11,325 kJ (2705 kcal) per day, respectively] and contributed 23% less energy than 75 g of walnuts. Approximately, 86% and 85% of the total fat and saturated fatty acids from walnuts were not displaced, whereas the increase in fibre from the usual diet to the actual walnut supplement diet represented less than one-half (39%) of the fibre provided by 75 g of walnuts. Walnuts were substituted, in part, for other foods, and the nutrient profile of the diet was improved, however, the beneficial effect of walnuts on the diet quality was not optimized. CONCLUSIONS: Individuals do not optimally implement food-based guidance. Consequently, nutrition professionals play a key role in teaching the implementation of food-based recommendations.

Outcomes of acetabular fracture fixation with ten years' follow-up.

We report the outcome of 161 of 257 surgically fixed acetabular fractures. The operations were undertaken between 1989 and 1998 and the patients were followed for a minimum of ten years. Anthropometric data, fracture pattern, time to surgery, associated injuries, surgical approach, complications and outcome were recorded. Modified Merle D'Aubigné score and Matta radiological scoring systems were used as outcome measures. We observed simple fractures in 108 patients (42%) and associated fractures in 149 (58%). The result was excellent in 75 patients (47%), good in 41 (25%), fair in 12 (7%) and poor in 33 (20%). Poor prognostic factors included increasing age, delay to surgery, quality of reduction and some fracture patterns. Complications were common in the medium- to long-term and functional outcome was variable. The gold-standard treatment for displaced acetabular fractures remains open reduction and internal fixation performed in dedicated units by specialist surgeons as soon as possible.

Heterogeneity of reporting standards in randomised clinical trials of endovenous interventions for varicose veins.

AIMS: The efficacy of endovenous treatments for venous reflux has been demonstrated in numerous randomised clinical trials, although significant heterogeneity may exist between studies. The aim of this study was to assess the heterogeneity in reporting between randomised clinical trials investigating endovenous treatments for patients with varicose veins. METHODS: A literature search of the Pubmed, Cochrane and Google Scholar databases was performed using appropriate search terms. Randomised clinical trials published between January 1968 and June 2009 evaluating endovenous interventions for varicose veins were included and relevant abstracts and full text articles were reviewed. Published study reports were evaluated against recommended reporting standards published by the American Venous Forum in 2007. RESULTS: Twenty-eight randomised trials fulfilled the inclusion criteria. Median patient age (reported in 20/28 studies) ranged from 33 to 54 years. The CEAP classification was presented in 17/28 studies and the proportion of patients with C2 disease ranged from 6.3% to 83.5%. A total of 31 different outcome measures were utilised. This included 13 different questionnaires, varicose vein recurrence at 38 time points and 30 categories of complications. Duplex ultrasonography was used in 21/28 trials to assess recurrence. Quality of life was only evaluated in 11 studies and the follow-up period ranged from 3 weeks to 10 years. CONCLUSIONS: Meaningful comparison across randomised studies of endovenous treatments is made difficult by considerable variations in study populations and outcome measures between trials. This highlights the need for the use of prospectively agreed population selection, and reporting standards for outcome measures in randomised clinical assessments of new treatments.

A biomechanical basis for tears of the human acetabular labrum.

OBJECTIVE: Acetabular labral tears predominantly affect young patients and are a source of hip pain in the athlete. Four causes of the initiation of labral tears have been proposed; trauma, hypolaxity of the anterior capsule, dysplasia and bony impingement. A further cause could be reduced biomechanical properties in the area most susceptible to tears. However, no work has defined these properties. DESIGN: 32 compressive and 32 tensile test samples were harvested from fresh-frozen cadaveric acetabula. The labrum was divided into eight areas to allow comparison around its circumference. Semiconfined compressive testing and tensile testing were performed at a displacement rate of 10 mm/min in a controlled environment of 100% humidity at 37 (SD 1) degrees C. SETTING: Cadaveric study. RESULTS: The mean compressive stiffness was 31.75 (SD 16.7) MPa, and the mean tensile elastic modulus was 24.7 (SD 10.8) MPa. The anterosuperior region had a significantly lower compressive elastic modulus than either of the posterior quadrants (p<0.05) and a significantly lower tensile modulus to the anterioinferior area (p<0.05). CONCLUSIONS: The biomechanical properties in the anterosuperior region may be a contributing factor to the initiation of labral tears.

Fracture healing in HIV-positive populations.

Highly active anti-retroviral therapy has transformed HIV into a chronic disease with a long-term asymptomatic phase. As a result, emphasis is shifting to other effects of the virus, aside from immunosuppression and mortality. We have reviewed the current evidence for an association between HIV infection and poor fracture healing. The increased prevalence of osteoporosis and fragility fractures in HIV patients is well recognised. The suggestion that this may be purely as a result of highly active anti-retroviral therapy has been largely rejected. Apart from directly impeding cellular function in bone remodelling, HIV infection is known to cause derangement in the levels of those cytokines involved in fracture healing (particularly tumour necrosis factor-alpha) and appears to impair the blood supply of bone. Many other factors complicate this issue, including a reduced body mass index, suboptimal nutrition, the effects of anti-retroviral drugs and the avoidance of operative intervention because of high rates of wound infection. However, there are sound molecular and biochemical hypotheses for a direct relationship between HIV infection and impaired fracture healing, and the rewards for further knowledge in this area are extensive in terms of optimised fracture management, reduced patient morbidity and educated resource allocation. Further investigation in this area is overdue.

Glenohumeral motion: review of measurement techniques.

Measurement of upper limb motion is problematic, not least because of the large range of path dependent description of motion of the joints, and the multiple non-cyclical unstandardised motion tasks measured. Furthermore, appreciation of shoulder motion specifically is obscured by overlying soft tissue. In order to satisfy the complexity of a clinically useful model of the movement of the joint, input data must be acquired from a set of pre-determined movements using a non-invasive technique with a high level of accuracy. Descriptive and predictive modeling of the glenohumeral joint requires input of high-fidelity data into a 6 degree of freedom representation, without which, the application of the tool is of limited clinical significance to the advancement of both operative and non-operative management of shoulder pathology. Electromagnetic, linkage and radiographic techniques have previously been used, however, an optimal solution is yet to be described.

Increased vibrissa growth in transgenic mice expressing insulin-like growth factor 1.

Insulin-like growth factor 1 (IGF-1) mediates many of the actions of growth hormone. Overexpression of IGF-1 has been reported to have endocrine and paracrine/autocrine effects on somatic growth in transgenic mice. To study the paracrine/autocrine effects of IGF-1 in hair follicles, transgenic mice were produced by pronuclear microinjection of a construct containing a mouse ultra-high sulfur keratin (UHS-KER) promoter linked to an ovine IGF-1 cDNA. This UHS-KER promoter has previously been shown to direct expression of a reporter gene to the hair follicles of transgenic mice. Four transgenic mouse lines were established as a result of microinjection of 435 embryos. Transgene expression was found in skin at day 8 and day 15 of age in three of the lines. Progeny tests were carried out by mating two of the transgenic expressing males to nontransgenic females. Mice from one line were all nonexpressors while four of the 12 mice from the other showed integration of the transgene and three expressed transgene IGF-1 mRNA in the skin. Vibrissa growth at 11-21 d of age was significantly greater in transgenic expressors than in their nontransgenic littermates. Specifically, the increase in vibrissa length for transgenics at days 11-16 (20.5%) is approximately 2-fold compared with days 16-21 (11.9%). These results demonstrate that local overexpression of IGF-1 in transgenic mice is capable of stimulating vibrissa growth during the first neonatal hair cycle.

Correspondence between the effect of zidovudine plus lamivudine on plasma HIV level/CD4 lymphocyte count and the incidence of clinical disease in infected individuals. North American Lamivudine HIV Working Group.

OBJECTIVES: To investigate whether apparently beneficial changes in plasma HIV RNA level and CD4 lymphocyte count that are induced by antiretroviral therapy are associated with a corresponding clinical benefit. METHODS: For 620 patients in two randomized, double-blind trials of lamivudine (3TC) and zidovudine (ZDV) plasma HIV RNA and CD4 lymphocyte count changes were compared in patients randomized to 3TC plus ZDV and patients randomized to other treatment arms. The effect of therapy on the HIV RNA level and CD4 count was compared with the effect of therapy on clinical endpoints over the same time period. RESULTS: Median baseline values for all subjects were 42 420 copies/ml for HIV RNA and 277 x 10(6)/l for CD4 count. During the trial a significantly lower HIV RNA level and higher CD4 count was sustained in the ZDV/3TC group compared with the other group, with a difference in the median area under the curve from baseline per month of follow-up of 0.38 log10 copies/ml HIV RNA and 0.18 log2 x 10(6)/l CD4 cells (P < 0.001 in each case). For patients who were initially asymptomatic or in CDC stage B, the adjusted relative hazard (RH) of AIDS for a twofold lower CD4 count was 3.14 [95% confidence interval (CI), 1.44-6.83] and for a 10-fold higher HIV RNA level was 3.22 (1.20-8.59). The RH progression to AIDS expected with ZDV/3TC compared with the control treatments, given the observed effects of treatment on CD4 cell counts and HIV RNA levels, is 0.52, whereas the observed value was 0.16 (0.03-0.74). After adjustment for HIV RNA and CD4 changes over time the observed RH of progression to AIDS for ZDV/3TC treatment compared with controls was increased to 0.36 and was no longer significant (95% CI, 0.07-1.85). CONCLUSION: In this analysis of two trials, the effects of ZDV/3TC in reducing plasma HIV RNA and raising peripheral blood CD4 counts were associated with concurrent clinical benefits and the effect of treatment on these markers could account for at least part of the clinical benefits of therapy that were observed.

Intracellular calcium stores and inositol 1,4,5-trisphosphate receptor in rat liver cells.

The D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] receptor was localized by immunofluorescence experiments in situ in liver cryosections. Two anti-Ins(1,4,5)P3 receptor antibodies (against the 14 C-terminal residues of the type 1 receptor or against the entire cerebellar receptor) weakly decorated the whole cytoplasm, and a more intense labelling was observed at the periphery of the hepatocytes, particularly beneath the canalicular and the sinusoidal domains of the plasma membrane (PM). Antibodies against calreticulin, the Ca2+ pump (SERCA2b) or endoplasmic reticulum (ER) membranes homogeneously labelled the cytoplasm and the subplasmalemmal area. These data indicate that the ER can be divided into at least two specialized subregions: one is located throughout most of the cytoplasm and contains markers of the rough ER (RER), calreticulin, SERCA2b and a low density of Ins(1,4,5)P3 receptor, and the other is confined to the periphery of the cells and contains calreticulin, Ca2+ pump, RER markers and a high density of Ins(1,4,5)P3 receptor. A membrane fraction enriched in Ins(1,4,5)P3 receptor and in markers of the PM was immuno-adsorbed with the antibody against the C-terminal end of the Ins(1,4,5)P3 receptor and pelleted with Sepharose protein A. The immuno-isolated material was enriched in Ins(1,4,5)P3 receptor, but none of the markers of the ER or of the PM could be detected. This suggests that the Ins(1,4,5)P3 receptor is localized on discrete domains of the ER membrane beneath the canalicular and the sinusoidal membranes, where it was found at higher densities than the other markers.

Inhibition, tissue distribution and hormonal specificity of a promoter-binding factor for the uteroglobin gene.

We had earlier reported a uteroglobin promoter-binding factor in nuclei from progesterone-stimulated rabbit endometrium that was inhibited by a factor in nuclei without progesterone stimulation or from non-target tissues (Rider, V., and Bullock, D.W., 1988. Biochem. Biophys. Res. Comm. 156, 1368-1375). In the course of purification of the inhibitory activity, the effect was shown to be due to contaminating genomic DNA. The inhibitor was destroyed by treatment with DNase I and resisted phenol-chloroform extraction. Fractionation of nuclear extracts on columns of DEAE-Sepharose separated the inhibitor and revealed the presence of binding activity in unstimulated or estrogen-treated endometrium, as well as in liver, lung and ovary. The tissue and hormonal specificity of the promoter binding factor is thus less restricted than recently reported.

Oscillations of cytosolic free calcium concentration in the presence of intracellular antibodies to phosphatidylinositol 4,5-bisphosphate in voltage-clamped guinea-pig hepatocytes.

In liver cells, the stimulation of alpha 1-adrenoceptors by noradrenaline induces the production of Ins(1,4,5)P3 through the degradation of membrane polyphosphoinositides [PtdIns(4,5)P2]. InsP3 evokes in turn the release of Ca2+ from internal stores. Our results show that the internal perfusion of single guinea-pig hepatocytes with monoclonal anti-PtdInsP2 antibody blocks the rise in cytosolic free Ca2+ concn. ([Ca2+]i) evoked by noradrenaline, an InsP3-dependent agonist, but not by the monohydroxylated bile acid taurolithocholate 3-sulphate, which is known to permeabilize the endoplasmic reticulum. In these conditions, the bile acid elicited either fast or slow fluctuations of [Ca2+]i independently of any InsP3 production. The responses to the bile acid were also observed in the absence of external Ca2+. The presence of intracellular anti-PtdInsP2 antibody does not affect the response to a photolytic release of InsP3 (1.5 microM final concn.) from a caged precursor.

Regulation of microtubule dynamics and nucleation during polarization in MDCK II cells.

MDCK cells form a polarized epithelium when they reach confluence in tissue culture. We have previously shown that concomitantly with the establishment of intercellular junctions, centrioles separate and microtubules lose their radial organization (Bacallao, R., C. Antony, C. Dotti, E. Karsenti, E.H.K. Stelzer, and K. Simons. 1989. J. Cell Biol. 109:2817-2832. Buendia, B., M.H. Bré, G. Griffiths, and E. Karsenti. 1990. 110:1123-1136). In this work, we have examined the pattern of microtubule nucleation before and after the establishment of intercellular contacts. We analyzed the elongation rate and stability of microtubules in single and confluent cells. This was achieved by microinjection of Paramecium axonemal tubulin and detection of the newly incorporated subunits by an antibody directed specifically against the Paramecium axonemal tubulin. The determination of newly nucleated microtubule localization has been made possible by the use of advanced double-immunofluorescence confocal microscopy. We have shown that in single cells, newly nucleated microtubules originate from several sites concentrated in a region localized close to the nucleus and not from a single spot that could correspond to a pair of centrioles. In confluent cells, newly nucleated microtubules were still more dispersed. The microtubule elongation rate of individual microtubules was not different in single and confluent cells (4 microns/min). However, in confluent cells, the population of long lived microtubules was strongly increased. In single or subconfluent cells most microtubules showed a t1/2 of less than 30 min, whereas in confluent monolayers, a large population of microtubules had a t1/2 of greater than 2 h. These results, together with previous observations cited above, indicate that during the establishment of polarity in MDCK cells, microtubule reorganization involves both a relocalization of microtubule-nucleating activity and increased microtubule stabilization.

Cancer research in New Jersey.

The New Jersey State Commission on Cancer Research endeavors to support basic research in cancer by providing funds to New Jersey investigators. The Commission now is focusing attention on the important area of clinical research as well, including psychosocial and epidemiologic studies.

KIN, a mammalian nuclear protein immunologically related to E. coli RecA protein.

A polypeptide of about 120 kDa, called KIN, has been identified in rat FR 3T3 cells by immunoblotting using affinity-purified antibodies against the RecA protein of Escherichia coli (38 kDa). The KIN protein as shown by fluorescent light microscopy and electron microscopy is essentially concentrated in the nucleus. Its level is higher in proliferating than in quiescent cells. Cell treatment with mitomycin C increases the level of the KIN protein. We sought similar proteins in other mammalian cells. Proteins with the same electrophoretic mobility were detected in mouse, monkey and human cell lines as well as in rat and mouse embryos.

[Immunocytochemical localization in human spermatozoa of tubulin and the associated high molecular weight proteins MAP1 and MAP2]. / Localisation immunocytochimique dans le spermatozoïde humain de la tubuline et des protéines associées de haut poids moléculaire MAP1 et MAP2.

By immunofluorescent and immunoperoxidase techniques and with the use of highly purified antibodies, tubulin and its associated proteins, MAP1 and MAP2 have been identified and precisely localized in human spermatozoa. In relation to well known structural elements, tubulin appeared localized to the region of the axoneme, the centriolar adjunct and the equatorial part of the acrosome, in contrast MAP1 and MAP2 were localized to the post-nuclear region and in the fibrous sheath of the principal piece of the flagella.