Homocysteine levels and lacunar brain infarcts in elderly women: the prospective population study of women in Gothenburg.

OBJECTIVES: To examine whether total serum homocysteine (tHcy) in a population-based sample of middle-aged women is an independent risk factor for presence of lacunar infarcts (LIs) 24 years later. DESIGN: Prospective population study, follow-up time 24 years. SETTING: Gothenburg, an urban area in western Sweden. PARTICIPANTS: Five hundred twenty-six women, 89.6% of the original study sample of the Population Study of Women in Gothenburg, aged 46 to 60 at baseline in 1968/69 and re-examined at age 70 to 84. MEASUREMENTS: After 24 years of follow-up, all subjects underwent a psychiatric examination, and 277 computerized tomography (CT) scans of the brain were performed. Two radiologists assessed LIs and white matter lesions (WMLs). Baseline serum tHcy was analyzed from frozen stored serum samples. Logistic regression analyses were performed controlling for potential confounders such as age and selected cardiovascular risk factors. RESULTS: Thirty-four subjects had LIs in 1992 (12.3%). In the full multivariate-adjusted stepwise model, LIs were associated with elevated tHcy (odds ratio (OR)=1.09, 95% confidence interval (CI)=1.01-1.17 per micromol/L of tHcy increment). Women with tHcy values in the highest tertile were almost three times as likely to have LIs (OR=2.82, 95% CI=1.34-5.93) as were those in the lowest tertile. tHcy was not related to WMLs. Subjects who did not undergo a CT scan did not differ from those who did regarding tHcy or any of the covariates studied. CONCLUSION: tHcy in middle-aged women is an independent risk factor for LIs, but not WMLs, as observed using CT later in life.

Clinical evaluation of the zygoma implant: 3-year follow-up at 16 clinics.

PURPOSE: The purpose of this clinical investigation was to evaluate the treatment outcome with zygoma implants with regard to implant survival, patient satisfaction, and function of prosthesis replacement after 3 years. PATIENTS AND METHODS: The treatment outcome of 76 patients treated with 145 zygoma fixtures at 16 centers was evaluated with regard to implant survival. Status of peri-implant mucosa and amount of plaque were registered annually. Patients' and dentists' evaluations of the functional and esthetic outcome of the treatment were assessed at delivery of prosthesis and thereafter at each follow-up visit. RESULTS: Sixty of 76 patients were followed for 3 years after prosthetic delivery. Five of 145 placed zygoma implants failed during the course of the study resulting in an overall implant survival rate of 96.3%. At the 3-year follow-up, 75% of the implants sites were registered with normal peri-implant mucosa and 68% with no visible plaque. The patients were fully satisfied with the esthetic and functional outcome of the treatment in 86% and 71%, respectively, at the 3-year follow-up visit. All reported data from dentists scored from acceptable to excellent. CONCLUSION: The multicenter study showed a high predictability of the zygoma implant-supported rehabilitation.

Bromide does not bind to the Mn4Ca complex in its S1 state in Cl(-)-depleted and Br(-)-reconstituted oxygen-evolving photosystem II: evidence from X-ray absorption spectroscopy at the Br K-edge.

Chloride is an important cofactor in photosynthetic water oxidation. It can be replaced by bromide with retention of the oxygen-evolving activity of photosystem II (PSII). Binding of bromide to the Mn(4)Ca complex of PSII in its dark-stable S(1) state was studied by X-ray absorption spectroscopy (XAS) at the Br K-edge in Cl(-)-depleted and Br(-)-substituted PSII membrane particles from spinach. The XAS spectra exclude the presence of metal ions in the first and second coordination spheres of Br(-). EXAFS analysis provided tentative evidence of at least one metal ion, which may be manganese or calcium, at a distance of approximately 5 A to Br(-). The native Cl(-) ion may bind at a similar distance. Accordingly, water oxidation may not require binding of a halide directly to the metal ions of the Mn complex in its S(1) state.

High-grade astrocytoma treated concomitantly with estramustine and radiotherapy.

Experimental and early clinical investigations have demonstrated encouraging results for estramustine in the treatment of malignant glioma. The present study is an open randomized clinical trial comparing estramustine phosphate (Estracyt) in addition to radiotherapy with radiotherapy alone as first line treatment of astrocytoma grade III and IV. The 140 patients included were in a good clinical condition with a median age of 55 years (range 22-87). Estramustine was given orally, 280 mg twice daily, as soon as the diagnosis was established, during and after the radiotherapy for a period of in total 3 months. Radiotherapy was delivered on weekdays 2 Gy daily up to 56 Gy. Eighteen patients were excluded due to misclassification, leaving 122 patients eligible for evaluation. Overall the treatment was well tolerated. Mild or moderate nausea was the most common side effect of estramustine. The minimum follow-up time was 5.2 years for the surviving patients. For astrocytoma grade III the median survival time was 10.6 (1.3-92.7) months for the radiotherapy only group and 17.3 (0.4-96.9+) months for the estramustine + radiotherapy group. In grade IV the corresponding median survival time was 12.3 (2.1-89.2) and 10.3 (0.3-91.7+) months, respectively. Median time to progress for radiotherapy only and radiotherapy and estramustin group in grade III tumours was 6.5 and 10.1 months, respectively. In grade IV tumours the corresponding figures were 5.1 and 3.3 months, respectively. Although there was a tendency for improved survival in grade III, no statistical significant differences were found between the treatment groups. No differences between the two treatment groups were evident with respect to quality of life according to the EORTC QLQ-protocol. In conclusion, this first randomized study did not demonstrate any significant improvement of using estramustine in addition to conventional radiotherapy, however, a trend for a positive response for the estramustine group was found in patients with grade III glioma.

Conformational regulation of charge recombination reactions in a photosynthetic bacterial reaction center.

In bright light the photosynthetic reaction center (RC) of Rhodobacter sphaeroides stabilizes the P(+)(870).Q(-)(A) charge-separated state and thereby minimizes the potentially harmful effects of light saturation. Using X-ray diffraction we report a conformational change that occurs within the cytoplasmic domain of this RC in response to prolonged illumination with bright light. Our observations suggest a novel structural mechanism for the regulation of electron transfer reactions in photosynthesis.

A clinical evaluation of the Zygoma fixture: one year of follow-up at 16 clinics.

PURPOSE: To evaluate treatment outcome with Zygoma fixtures (Nobel Biocare, Göteborg, Sweden) with regard to fixture survival, patient satisfaction, and function of prosthesis replacement. MATERIALS AND METHODS: The treatment outcome of 76 patients treated with 145 Zygoma fixtures at 16 centers was evaluated. Patient's and dentist's evaluations of the functional and aesthetic outcome of the treatment were assessed at delivery of prosthesis and at the 1-year follow-up visit. At the 1-year follow-up visit, the status of the peri-implant mucosa around the abutments and the amount of plaque were registered. RESULTS: Sixty-six of the 76 patients, with 124 Zygoma fixtures supporting the prosthetic restorations, were evaluated at the 1-year follow-up. The overall survival rate for the Zygoma fixtures was 97.9% after 1-year of follow-up. Eighty percent of the patients were fully satisfied with both aesthetic and functional outcome at the time of prosthetic insertion and at the 1-year follow-up. All reported data from the dentists, with the exception of one restoration with several abutment screw loosenings, scored from acceptable to excellent for the aesthetic and functional outcome of the treatment. The status of peri-implant mucosa was recorded as normal in approximately 60% of the sites. Plaque, when present, was more often detected on the palatal surfaces compared with the buccal surfaces. CONCLUSION: This 1-year follow-up of Zygoma fixtures has shown good results with an acceptable number of minor complications and a majority of satisfied patients.

Basal ganglia calcification and psychotic symptoms in the very old.

BACKGROUND: Basal ganglia calcification (BGC) is associated with psychotic symptoms in young and middle-aged patient samples. METHODS: We studied the cross-sectional relationship between psychotic symptoms and BGC in a population sample of non-demented 85-year-olds, of whom 86 were mentally healthy, 11 had hallucinations or delusions, 21 had mood disorders and 20 had anxiety disorders. BGC was measured using computerized tomography (CT). Mental disorders were diagnosed using DSM-III-R criteria and psychotic symptoms were evaluated using information from psychiatric examinations, key-informant interviews and review medical records. RESULTS: BGC on CT was observed in 19% of mentally healthy and 64% of non-demented individuals with hallucinations or delusions [Odds Ratio (OR) 7.7, 95% Confidence Intervals (CI) 2.9-29.7, p=0.003]. There were no associations between BGC and mood or anxiety disorders. CONCLUSIONS: BGC is strongly associated with psychotic symptoms in very old age, possibly due to a disturbance in the basal ganglia dopaminergic system.

Spectroscopic characterization of a semi-stable, charge-separated state in Cu(2+)-substituted reaction centers from Rhodobacter sphaeroides.

In reaction centers from Rhodobacter sphaeroides exposed to continuous illumination in the presence of an inhibitor of the Q(A)(-) to Q(B) electron transfer, a semi-stable, charge-separated state was formed with halftimes of formation and decay of several minutes. When the non-heme iron was replaced by Cu(2+), the decay of the semi-stable, charge-separated state became much slower than in centers with bound Fe(2+) with about the same rate constant for formation. In Cu(2+)-substituted reaction centers, the semi-stable state was associated with an EPR signal, significantly different from that observed after chemical reduction of the acceptor-side quinone or after illumination at low temperature, but similar to that of an isolated Cu(2+) in the absence of magnetic interaction. The EPR results, obtained with Cu(2+)-substituted reaction centers, suggest that the slow kinetics of formation and decay of the charge-separated, semi-stable state is associated with a structural rearrangement of the acceptor side and the immediate environment of the metal-binding site.

Lipidic cubic phase crystal structure of the photosynthetic reaction centre from Rhodobacter sphaeroides at 2.35A resolution.

Well-ordered crystals of the bacterial photosynthetic reaction centre from Rhodobacter sphaeroides were grown from a lipidic cubic phase. Here, we report the type I crystal packing that results from this crystallisation medium, for which 3D crystals grow as stacked 2D crystals, and the reaction centre X-ray structure is refined to 2.35A resolution. In this crystal form, the location of the membrane bilayer could be assigned with confidence. A cardiolipin-binding site is found at the protein-protein interface within the membrane-spanning region, shedding light on the formation of crystal contacts within the membrane. A chloride-binding site was identified in the membrane-spanning region, which suggests a putative site for interaction with the light-harvesting complex I, the cytochrome bc(1) complex or PufX. Comparisons with the X-ray structures of this reaction centre deriving from detergent-based crystals are drawn, indicating that a slight compression occurs in this lipid-rich environment.

The function of the chloride ion in photosynthetic oxygen evolution.

The involvement of Cl(-) and several other monovalent anions in photosynthetic oxygen evolution was studied using photosystem II membranes depleted of Cl(-) by dialysis. The results of these studies differ significantly from results obtained using other depletion methods. Binding studies with glycerol as a cryoprotectant confirm our previous observations with sucrose of two interconvertible binding states of photosystem II with similar activities and with slow or fast exchange, respectively, of the bound ion. With glycerol, Cl(-) depletion decreased the oxygen evolution rate to 55% of that with Cl(-) present without decreasing the quantum efficiency of the reaction, supporting our previous conclusion that oxygen evolution can proceed at high rates in the absence of Cl(-). Further, after Cl(-) depletion the S(2) state multiline signal displayed the same periodic appearance with the same signal yield after consecutive laser flashes as with Cl(-) present. Br(-), I(-), and NO(3)(-), although with different capacities to reactivate oxygen evolution, also showed two binding modes. I(-) inhibited when bound in the low-affinity, fast-exchange mode but activated in the high-affinity mode. A comparison of the EPR properties of the S(2) state with these anions suggests that the nature of the ion or the binding mode only has a minor influence on the environment of the manganese. In contrast, F(-) completely inhibited oxygen evolution by preventing the S(2) to S(3) transition and shifted the equilibrium between the g = 4.1 and multiline S(2) forms toward the former, which suggests a considerable perturbation of the manganese cluster. To explain these and earlier observations, we propose that the role of chloride in the water-splitting mechanism is to participate together with charged amino acid side chains in a proton-relay network, which facilitates proton transfer from the manganese cluster to the medium. The structural requirements likely to be involved may explain the sensitivity of oxygen evolution to Cl(-) depletion or other perturbations.

Characterization of a semi-stable, charge-separated state in reaction centers from Rhodobacter sphaeroides.

In reaction centers from Rhodobacter sphaeroides, subjected to continuous illumination in the presence of an inhibitor of the Q(A) to Q(B) electron transfer, the oxidation of P870 consisted of several kinetic phases with a fast initial reaction followed by very slow accumulation of P870(+) with a halftime of several minutes. When the light was turned off, a phase of fast charge recombination was followed by an equally slow reduction of P870(+). In reaction centers depleted of Q(B), where forward electron transfer from Q(A) is also prevented, the slow reactions were also observed but with different kinetic properties. The kinetic traces of accumulation and decay of P870(+) could be fitted to a simple three-state model where the initial, fast charge separation is followed by a slow reversible conversion to a long-lived, charge-stabilized state. Spectroscopic examination of the charge-separated, semi-stable state, using optical absorbance and EPR spectroscopy, suggests that the unpaired electron on the acceptor side is located in an environment significantly different from normal. The activation parameters and enthalpy and entropy changes, determined from the temperature dependence of the slow conversion reaction, suggest that this might be coupled to changes in the protein structure of the reaction centers, supporting the spectroscopic results. One model that is consistent with the present observations is that reaction centers, after the primary charge separation, undergo a slow, light-induced change in conformation affecting the acceptor side.